Endothelin-1

内皮素 - 1
  • 文章类型: Journal Article
    背景:新生儿呼吸窘迫综合征(NRDS)是新生儿重症监护病房中最常见的疾病之一,婴儿发病率约为7%。此外,它是中国医院新生儿死亡的主要原因。该疾病的主要机制是缺乏表面活性剂引起的低氧血症和高碳酸血症。
    目的:探讨肺表面活性物质(PS)联合无创正压通气对外周血角蛋白-14(KRT-14)和内皮素-1(ET-1)水平的影响及治疗NRDS的疗效。
    方法:选取我院2019年4月至2021年7月收治的呼吸窘迫综合征新生儿137例。其中,对照组64例采用无创正压通气治疗,观察73例采用PS联合无创正压通气治疗。比较两组患者KRT-14和ET-1的表达情况。死亡,并发症,比较两组患者的PaO2、PaCO2、PaO2/FiO2血气指标。采用受试者工作特征曲线(ROC)分析确定KRT-14和ET-1在NRDS治疗中的诊断价值。
    结果:观察组显效率明显高于对照组。两组新生儿死亡率和不良反应无显著性差异,如支气管发育不良,紫癜,呼吸急促.治疗后,两组患者PaO2和PaO2/FiO2水平均明显高于治疗前,而PaCO2水平明显降低。治疗后,观察组PaO2和PaO2/FiO2水平明显高于对照组,观察组PaCO2明显低于对照组。治疗后,与治疗前相比,两组的KRT-14和ET-1水平均显着降低。观察组KRT-14、ET-1水平较对照组降低。ROC曲线分析显示,KRT-14的曲线下面积(AUC)为0.791,ET-1的AUC为0.816。
    结论:PS联合无创正压通气可显著提高NRDS治疗的有效性。KRT-14和ET-1水平可能具有作为治疗和诊断指标的潜力。
    BACKGROUND: Neonatal respiratory distress syndrome (NRDS) is one of the most common diseases in neonatal intensive care units, with an incidence rate of about 7% among infants. Additionally, it is a leading cause of neonatal death in hospitals in China. The main mechanism of the disease is hypoxemia and hypercapnia caused by lack of surfactant.
    OBJECTIVE: To explore the effect of pulmonary surfactant (PS) combined with noninvasive positive pressure ventilation on keratin-14 (KRT-14) and endothelin-1 (ET-1) levels in peripheral blood and the effectiveness in treating NRDS.
    METHODS: Altogether 137 neonates with respiratory distress syndrome treated in our hospital from April 2019 to July 2021 were included. Of these, 64 control cases were treated with noninvasive positive pressure ventilation and 73 observation cases were treated with PS combined with noninvasive positive pressure ventilation. The expression of KRT-14 and ET-1 in the two groups was compared. The deaths, complications, and PaO2, PaCO2, and PaO2/FiO2 blood gas indexes in the two groups were compared. Receiver operating characteristic curve (ROC) analysis was used to determine the diagnostic value of KRT-14 and ET-1 in the treatment of NRDS.
    RESULTS: The observation group had a significantly higher effectiveness rate than the control group. There was no significant difference between the two groups in terms of neonatal mortality and adverse reactions, such as bronchial dysplasia, cyanosis, and shortness of breath. After treatment, the levels of PaO2 and PaO2/FiO2 in both groups were significantly higher than before treatment, while the level of PaCO2 was significantly lower. After treatment, the observation group had significantly higher levels of PaO2 and PaO2/FiO2 than the control group, while PaCO2 was notably lower in the observation group. After treatment, the KRT-14 and ET-1 levels in both groups were significantly decreased compared with the pre-treatment levels. The observation group had a reduction of KRT-14 and ET-1 levels than the control group. ROC curve analysis showed that the area under the curve (AUC) of KRT-14 was 0.791, and the AUC of ET-1 was 0.816.
    CONCLUSIONS: Combining PS with noninvasive positive pressure ventilation significantly improved the effectiveness of NRDS therapy. KRT-14 and ET-1 levels may have potential as therapeutic and diagnostic indicators.
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  • 文章类型: Journal Article
    OBJECTIVE: To observe the effects of acupuncture at \"antihypertensive acupoint prescription\" on endothelial active factors and related autonomic neurotransmitters in spontaneous hypertension rats, and explore the vascular regulation and central regulation mechanisms of acupuncture for anti-hypertension.
    METHODS: Thirty SPF grade male spontaneous hypertension rats were randomly divided into a model group (15 rats) and an acupuncture group (15 rats). Besides, 15 Wistar Kyoto rats were collected as a blank control group (normal group). In the acupuncture group, acupuncture was delivered at the \"antihypertensive acupoint prescription\" (bilateral \"Renying\" [ST 9], \"Quchi\" [LI 11], \"Zusanli\" [ST 36], \"Taichong\" [LR 3] and \"Neiguan\" [PC 6]), with needles retained for 30 min, once daily. The duration of intervention was 28 days. Every week, using the the irritation scale, the sign of sympathetic irritation was evaluated dynamically. The arterial blood pressure of the rats tail was determined, using non-invasive blood pressure measurement system. ELISA was adopted to detect the levels of calcitonin gene-related peptide (CGRP), nitric oxide (NO), endothelin-1 (ET-1), neuropeptide Y (NPY) in the serum. DAB chromogenic in situ hybridization (CISH) was provided to detect the mRNA expression of endothelial nitric oxide synthase (eNOS) in the internal carotid artery and the arcuate nucleus (ARC), and that of CGRP in the paraventricular nucleus posterior (PVP) and the ventrolateral medulla (VLM). Liquid chromatography-mass spectrometry (LC-MS) was used to detect the levels of epinephrine (E) and norepinephrine (NE) in the paraventricular nucleus anterior (PVA).
    RESULTS: Compared with the normal group, the irritation scores, systolic blood pressure and diastolic blood pressure were increased at each time point in the model group (P<0.05). When compared with the model group, the irritation scores after the intervention for 3 and 4 weeks, and systolic and diastolic blood pressure after intervention for 2, 3 and 4 weeks were reduced in the acupuncture group (P<0.05). In comparison with the normal group, the serum CGRP and NO levels of the rats were decreased (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels in PVA were increased (P<0.05) in the model group. The levels of serum CGRP and NO were elevated (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels of PVA were reduced (P<0.05) in the acupuncture group when compared with those of the model group. In the model group, the media of internal carotid artery exhibited thickening and remodeling, while the neuron volume in ARC was small. In the acupuncture group, every layer of internal carotid artery was acceptably arranged, and the parvicellular neuron of ARC was moderate in volume. For the in situ hybridization of eNOS mRNA for the rats of each group, the smooth muscle cells were predominantly expressed in each layer of the internal carotid artery, whereas the expression of parvicellular neurons was dominated in ARC. In the model group, the large and small neurosecretory cells were distributed sparsely in the nerves of PVP; in the acupuncture group, the cells of these two species were distributed regularly; and there were few species of glial cell in the VLM of either the model group or the acupuncture group. In each group, for the in situ hybridization of CGRP mRNA, the small neurosecretory cells were expressed predominately in the PVP, while, the expression of glial cell nuclei and the cell cytoplasm was dominated in the VLM. Compared with the normal group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP mRNA in the PVP and VLM was decreased in the model group (P<0.05). In the acupuncture group, when compared with the model group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP in the PVP and VLM was increased in the acupuncture group (P<0.05).
    CONCLUSIONS: Acupuncture at \"antihypertensive acupoint prescription\" can upregulate the level of vascular relaxing factors, downregulate the level of contracting factors, enhance the response of relaxing factors in targeting blood vessels and regulating the center. The mechanism may be related to the modulation of the sympathetic-adrenergic autonomic neurotransmitters in the paraventricular nucleus in spontaneous hypertension rats.
    目的:观察针刺“降压方”对自发性高血压大鼠(SHR)内皮活性因子及相关自主神经递质的影响,探讨针刺降压的血管调节和中枢调控机制。方法:将30只SPF级雄性SHR随机分为模型组(15只)、针刺组(15只),另以15只京都种Wistar大鼠(WKR)为空白对照组(正常组)。针刺组予“降压方”(双侧“人迎”“曲池”“足三里”“太冲”“内关”)针刺,留针30 min,每日1次,共干预28 d。每周采用激惹评分动态评价大鼠交感激惹表征;通过全自动无创血压测量系统检测大鼠尾动脉血压;ELISA法检测血清降钙素基因相关肽(CGRP)、一氧化氮(NO)、内皮素-1(ET-1)、神经肽Y(NPY)含量;DAB显色原位杂交(CISH)检测颈内动脉、弓状核内皮型一氧化氮合酶(eNOS)及室旁核后部、延髓腹外侧CGRP mRNA表达;液相色谱及质谱联用检测室旁核前部肾上腺素(E)、去甲肾上腺素(NE)含量。结果:与正常组比较,模型组大鼠观察期间各时间点激惹评分及收缩压、舒张压升高(P<0.05);与模型组比较,针刺组大鼠干预第3、4周后激惹评分及干预第2、3、4周后收缩压、舒张压降低(P<0.05)。与正常组比较,模型组大鼠血清CGRP、NO含量降低(P<0.05),血清ET-1、NPY含量及室旁核前部E、NE含量升高(P<0.05);与模型组比较,针刺组大鼠血清CGRP、NO含量升高(P<0.05),血清ET-1、NPY含量及室旁核前部E、NE含量降低(P<0.05)。模型组大鼠颈内动脉中膜增厚且有重构表现,弓状核神经元体积较小;针刺组大鼠颈内动脉各层排布尚可,弓状核小细胞神经元适中。各组大鼠eNOS mRNA在颈内动脉主要表达于各层中平滑肌细胞,而在弓状核主要表达于小细胞神经元。模型组大鼠室旁核后部神经分泌大细胞及小细胞分布较为稀疏,针刺组大鼠两类细胞排布尚可;模型组、针刺组大鼠延髓腹外侧区胶质细胞种类相对较少。各组大鼠CGRP mRNA在室旁核后部主要表达于神经分泌小细胞,而在延髓腹外侧主要表达于胶质细胞核及细胞质。与正常组比较,模型组大鼠颈内动脉及弓状核eNOS mRNA、室旁核后部及延髓腹外侧CGRP mRNA表达降低(P<0.05);与模型组比较,针刺组大鼠颈内动脉及弓状核eNOS mRNA、室旁核后部及延髓腹外侧CGRP mRNA表达增加(P<0.05)。结论:针刺“降压方”可上调血管舒张因子水平,下调血管收缩因子水平,同时增强血管舒缩因子靶向血管及调控中枢的响应,其机制可能与调节SHR室旁核交感肾上腺素能自主神经递质有关。.
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  • 文章类型: Journal Article
    背景:血管失调是青光眼的主要危险因素之一,内皮素-1(ET-1)可能在血管性青光眼的发病机制中起作用。枸杞果实提取物(LB)在各种动物模型中表现出抗衰老和保护视网膜神经节细胞(RGC)的多靶点机制。探讨LB糖蛋白(LbGP)在ET-1诱导的RGC变性中的疗效,在预处理和后处理条件下将LbGP应用于ET-1小鼠模型。使用基于临床的技术表征视网膜结构和功能结果。
    方法:将成年C57BL/6小鼠随机分为四个实验组,即车辆控制(n=9),LbGP预处理(n=8),LbGP-后处理(第1天)(n=8)和LbGP-后处理(第5天)(n=7)。每天一次口服施用lmg/Kg的LbGP或用于载体对照的PBS。治疗前和治疗后(第1天或第5天)在玻璃体内注射前1周和后1或5天开始,分别,并持续到注射后第28天。使用光学相干断层扫描(OCT)评估治疗对视网膜结构和功能的影响,基线时多普勒OCT和视网膜电图测量,注射后第10天和第28天。通过在视网膜整体上使用RBPMS免疫染色来评估RGC存活。
    结果:在媒介物对照中注射ET-1引起动脉流量和视网膜功能的短暂减少,在第28天导致显著的RNFL变薄和RGC损失。尽管在所有LbGP组中ET-1引起血流或视网膜功能的短暂丧失,与载体对照相比,LbGP治疗促进更好地恢复视网膜血流和视网膜功能。此外,所有三个LbGP治疗组(即从第1天或第5天的治疗前和治疗后)均显著保留了RNFL厚度和RGC密度。在三个LbGP治疗组之间没有观察到保护作用的显著差异。
    结论:LbGP在ET-1诱导的RGC变性小鼠模型中显示出神经保护作用,将治疗作为预处理,立即或延迟后治疗。LbGP治疗促进了视网膜血流的更好恢复,并保护了RNFL,RGC密度和视网膜功能。这项研究显示了LB作为青光眼治疗的补充治疗的转化潜力。
    BACKGROUND: Vascular dysregulation is one of the major risk factors of glaucoma, and endothelin-1 (ET-1) may have a role in the pathogenesis of vascular-related glaucoma. Fruit extract from Lycium Barbarum (LB) exhibits anti-ageing and multitarget mechanisms in protecting retinal ganglion cells (RGC) in various animal models. To investigate the therapeutic efficacy of LB glycoproteins (LbGP) in ET-1 induced RGC degeneration, LbGP was applied under pre- and posttreatment conditions to an ET-1 mouse model. Retina structural and functional outcomes were characterised using clinical-based techniques.
    METHODS: Adult C57BL/6 mice were randomly allocated into four experimental groups, namely vehicle control (n = 9), LbGP-Pretreatment (n = 8), LbGP-Posttreatment (day 1) (n = 8) and LbGP-Posttreatment (day 5) (n = 7). Oral administration of LbGP 1 mg/Kg or PBS for vehicle control was given once daily. Pre- and posttreatment (day 1 or 5) were commenced at 1 week before and 1 or 5 days after intravitreal injections, respectively, and were continued until postinjection day 28. Effects of treatment on retinal structure and functions were evaluated using optical coherence tomography (OCT), doppler OCT and electroretinogram measurements at baseline, post-injection days 10 and 28. RGC survival was evaluated by using RBPMS immunostaining on retinal wholemounts.
    RESULTS: ET-1 injection in vehicle control induced transient reductions in arterial flow and retinal functions, leading to significant RNFL thinning and RGC loss at day 28. Although ET-1 induced a transient loss in blood flow or retinal functions in all LbGP groups, LbGP treatments facilitated better restoration of retinal flow and retinal functions as compared with the vehicle control. Also, all three LbGP treatment groups (i.e. pre- and posttreatments from days 1 or 5) significantly preserved thRNFL thickness and RGC densities. No significant difference in protective effects was observed among the three LbGP treatment groups.
    CONCLUSIONS: LbGP demonstrated neuroprotective effects in a mouse model of ET-1 induced RGC degeneration, with treatment applied either as a pretreatment, immediate or delayed posttreatment. LbGP treatment promoted a better restoration of retinal blood flow, and protected the RNFL, RGC density and retinal functions. This study showed the translational potential of LB as complementary treatment for glaucoma management.
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  • 文章类型: Journal Article
    背景:患有人类免疫缺陷病毒(PWH)的人患有微血管疾病。因为血管周围脂肪组织(PVAT)调节微血管功能,并且在PWH中脂肪组织发炎,我们检验了PWH使PVAT发炎从而损害其小血管功能的假设。
    方法:从11名年龄<50岁的接受HIV治疗(WWH)的女性和10名没有HIV的配对女性的臀部皮肤活检中解剖有或没有PVAT的皮下小动脉,并在等距肌电图上进行了研究。通过荧光显微镜测量一氧化氮(NO)和活性氧(ROS)。在PVAT中测定脂肪因子和炎症标记物以及ROS。
    结果:对照妇女小动脉周围的PVAT显着(P<0.05)增强了乙酰胆碱诱导的内皮依赖性舒张和NO,和减少收缩血栓素和内皮素-1。然而,在PVAT释放较少的脂联素但更多的ROS和炎症标志物的WWH中,PVAT的这些作用显著降低(P<.05)。PVAT调节收缩与脂肪脂联素呈正相关。
    结论:来自WWH的PVAT具有氧化应激,炎症,脂联素的释放减少,这可能有助于增强收缩,因此可能促进小动脉功能障碍。
    BACKGROUND: People with the human immunodeficiency virus (PWH) have microvascular disease. Because perivascular adipose tissue (PVAT) regulates microvascular function and adipose tissue is inflamed in PWH, we tested the hypothesis that PWH have inflamed PVAT that impairs the function of their small vessels.
    METHODS: Subcutaneous small arteries were dissected with or without PVAT from a gluteal skin biopsy from 11 women with treated HIV (WWH) aged < 50 years and 10 matched women without HIV, and studied on isometric myographs. Nitric oxide (NO) and reactive oxygen species (ROS) were measured by fluorescence microscopy. Adipokines and markers of inflammation and ROS were assayed in PVAT.
    RESULTS: PVAT surrounding the small arteries in control women significantly (P < .05) enhanced acetylcholine-induced endothelium-dependent relaxation and NO, and reduced contractions to thromboxane and endothelin-1. However, these effects of PVAT were reduced significantly (P < .05) in WWH whose PVAT released less adiponectin but more markers of ROS and inflammation. Moderation of contractions by PVAT were correlated positively with adipose adiponectin.
    CONCLUSIONS: PVAT from WWH has oxidative stress, inflammation, and reduced release of adiponectin, which may contribute to enhanced contractions and therefore could promote small-artery dysfunction.
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  • 文章类型: Journal Article
    考虑到总胆固醇(TC)和血管内皮素-1(ET-1)对儿童脓毒症结局的显著影响,本研究旨在探讨血浆胆固醇和血管内皮素-1水平与脓毒症严重程度之间的关系,并评估其临床意义。在这项研究中,我们检查了2019年2月至2021年4月间诊断为脓毒症的250例儿科患者,收集了他们血浆TC和ET-1水平的数据.根据观察到的结果,参与者分为2类:预后阳性的组(对照组,n=100)和预后阴性的组(n=50)。我们评估了血浆TC和ET-1水平在预测这些儿科患者预后中的意义。预后不良组患者的住院时间明显长于对照组,治疗费用明显高于对照组(P<0.05)。在入院的最初24小时内以及第3天和第7天,预后不良组的ET-1水平显着升高,而血浆TC水平明显低于对照组(P<0.05)。Spearman相关分析确定血浆TC和ET-1水平与儿童败血症严重程度之间存在显着相关性(P<0.05)。儿童败血症严重程度的诊断表现,通过曲线下面积(AUC)测量,血浆TC为0.805,ET-1水平为0.777,和0.938,当两者结合。这项研究强调了小儿脓毒症患者血浆TC和ET-1水平之间有意义的关系,表明这些生物标志物在预测患者预后方面非常有价值。这些患者中高水平的ET-1和低水平的TC表示严重的病情和不良的预后。
    Considering the significant impact of total cholesterol (TC) and vascular endothelin-1 (ET-1) on children sepsis outcomes, this research aimed to explore the association between the levels of plasma cholesterol and vascular endothelin-1 and the severity of sepsis and evaluated its clinical implications. In this study, we examined 250 pediatric patients diagnosed with sepsis between February 2019 and April 2021, collecting data on their plasma levels of TC and ET-1. Depending on the observed outcomes, the participants were divided into 2 categories: a group with a positive prognosis (control group, n = 100) and a group with a negative prognosis (n = 50). We assessed the significance of plasma TC and ET-1 levels in forecasting the outcomes for these pediatric patients. Patients in the group with a poor prognosis experienced notably longer hospital stays and higher treatment expenses than those in the control group (P < .05). Within the first 24 hours of admission and again on days 3 and 7, the levels of ET-1 were significantly higher in the poor prognosis group, whereas plasma TC levels were notably lower in comparison to the control group (P < .05). A Spearman correlation analysis identified a significant correlation between the levels of plasma TC and ET-1 and the severity of sepsis among the children (P < .05). The diagnostic performance for the severity of sepsis in children, as measured by the area under the curve (AUC), was 0.805 for plasma TC, 0.777 for ET-1 levels, and 0.938 when both were combined. This investigation underscores a meaningful relationship between the levels of plasma TC and ET-1 in pediatric sepsis patients, suggesting these biomarkers are highly valuable in predicting patient outcomes. High levels of ET-1 and low levels of TC in these patients signify a grave condition and a poor prognosis.
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  • 文章类型: Journal Article
    OBJECTIVE: To observe the clinical effect of nape seven needles combined with pressing moxibustion for cervical vertigo (CV).
    METHODS: A total of 70 patients with CV were randomized into an observation group and a control group, 35 cases in each group. In the observation group, nape seven needles combined with pressing moxibustion was delivered, once a day, 6 times a week, for consecutive 2 weeks. In the control group, betahistine hydrochloride tablet and aceclofenac dispersible tablet were given orally, for 2 weeks and 3 days respectively. Before and after treatment, the evaluation scale for cervical vertigo (ESCV) score was observed, the plasma levels of neuropeptide Y (NPY), endothelin-1 (ET-1) and calcitonin gene related peptide (CGRP) were detected, the hemorheologic and hemodynamic indexes were measured, and the clinical efficacy was evaluated after treatment in the two groups.
    RESULTS: After treatment, the scores of dizziness, daily life and work ability, psychological and social adaptability, and headache, as well as the total scores of ESCV were increased compared with those before treatment (P<0.01, P<0.05) in the two groups, and the score and total score of neck and shoulder pain of ESCV was increased compared with that before treatment (P<0.01) in the observation group; each sub-item score and total score of ESCV in the observation group were higher than those in the control group (P<0.01, P<0.05). After treatment, the plasma levels of NPY and ET-1 were decreased compared with those before treatment (P<0.01), while the plasma levels of CGRP were increased compared with those before treatment (P<0.01, P<0.05) in the two groups; the plasma levels of NPY and ET-1 in the observation group were lower than those in the control group (P<0.01), the plasma level of CGRP in the observation group was higher than that in the control group (P<0.01). After treatment, the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity were decreased compared with those before treatment (P<0.01, P<0.05), the mean velocity of basilar artery (BA), left vertebral artery (LVA) and right vertebral artery (RVA) were increased compared with those before treatment (P<0.05) in the two groups; the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity in the observation group were lower than those in the control group (P<0.01), and the mean velocity of BA, LVA and RVA in the observation group were higher than those in the control group (P<0.05). The total effective rate in the observation group was 91.4% (32/35), which was superior to 71.4% (25/35) in the control group (P<0.05).
    CONCLUSIONS: Nape seven needles combined with pressing moxibustion can effectively alleviate the clinical symptoms, and improve the hemorheology and hemodynamics in CV patients.
    目的:观察项七针联合压灸治疗颈性眩晕(CV)的临床疗效。方法:将70例CV患者随机分为观察组和对照组,每组35例。观察组采用项七针联合压灸治疗,每日1次,每周6次,连续治疗2周。对照组予口服盐酸倍他司汀片(2周)和醋氯芬酸分散片(3 d)。分别于治疗前后观察两组患者颈性眩晕症状与功能评估量表(ESCV)评分,检测血浆神经肽Y(NPY)、内皮素-1(ET-1)、降钙素基因相关肽(CGRP)含量及血液流变学、血流动力学指标,并于治疗后评定两组临床疗效。结果:治疗后,两组患者ESCV眩晕、日常生活及工作能力、心理及社会适应能力、头痛评分及总分较治疗前升高(P<0.01,P<0.05),观察组患者颈肩痛评分较治疗前升高(P<0.01);观察组患者ESCV各项评分及总分均高于对照组(P<0.01,P<0.05)。治疗后,两组患者血浆NPY和ET-1含量较治疗前降低(P<0.01),血浆CGRP含量较治疗前升高(P<0.01,P<0.05);观察组患者血浆NPY、ET-1含量低于对照组(P<0.01),血浆CGRP含量高于对照组(P<0.01)。治疗后,两组患者全血高切黏度、血浆黏度、全血低切黏度均较治疗前降低(P<0.01,P<0.05),基底动脉(BA)、左侧椎动脉(LVA)、右侧椎动脉(RVA)平均血流速度均较治疗前升高(P<0.05);观察组患者全血高切黏度、血浆黏度及全血低切黏度均低于对照组(P<0.01),BA、LVA、RVA平均血流速度均高于对照组(P<0.05)。观察组总有效率为91.4%(32/35),高于对照组的71.4%(25/35,P<0.05)。结论:项七针联合压灸可有效减轻CV患者临床症状,改善血液流变学及血流动力学。.
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  • 文章类型: Journal Article
    石墨烯,通电时,产生波长范围为4μm至14μm的远红外辐射。该范围与远红外波段(3μm至15μm)紧密对齐,产生独特的生理效应。血管平滑肌的收缩和松弛在原发性高血压中起着重要作用,涉及一氧化氮可溶性鸟苷酸环化酶-环磷酸鸟苷途径和肾素-血管紧张素-醛固酮系统。这项研究利用自发性高血压大鼠(SHR)作为untr-HT来研究由带电石墨烯产生的特定波长的远红外辐射对血管平滑肌和血压的影响。7周后,untr-HT组大鼠血压明显下降,血管壁细胞数量和血管壁厚度明显减少,以及血管壁厚度与管腔直径的比率降低。此外,血流灌注明显增加,血管平滑肌肌球蛋白中F-actin的表达明显降低。血清血管紧张素Ⅱ(Ang-Ⅱ)和内皮素1(ET-1)水平显著降低,而一氧化氮合酶(eNOS)表达显著增加。在蛋白质水平,eNOS表达显著下降,而α-SMA在主动脉组织中的表达明显增加。在基因层面,主动脉组织中eNOS和α-SMA的表达明显增加。此外,SHR主动脉组织中一氧化氮(NO)含量显著升高。这些发现证实了石墨烯远红外辐射增强了微循环,调节影响血管平滑肌收缩的细胞因子,并改变血管形态和平滑肌表型,为原发性高血压提供救济。
    Graphene, when electrified, generates far-infrared radiation within the wavelength range of 4 μm to 14 μm. This range closely aligns with the far-infrared band (3 μm to 15 μm), which produces unique physiological effects. Contraction and relaxation of vascular smooth muscle play a significant role in primary hypertension, involving the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway and the renin-angiotensin-aldosterone system. This study utilized spontaneously hypertensive rats (SHRs) as an untr-HT to investigate the impact of far-infrared radiation at specific wavelengths generated by electrified graphene on vascular smooth muscle and blood pressure. After 7 weeks, the blood pressure of the untr-HT group rats decreased significantly with a notable reduction in the number of vascular wall cells and the thickness of the vascular wall, as well as a decreased ratio of vessel wall thickness to lumen diameter. Additionally, blood flow perfusion significantly increased, and the expression of F-actin in vascular smooth muscle myosin decreased significantly. Serum levels of angiotensin II (Ang-II) and endothelin 1 (ET-1) were significantly reduced, while nitric oxide synthase (eNOS) expression increased significantly. At the protein level, eNOS expression decreased significantly, while α-SMA expression increased significantly in aortic tissue. At the gene level, expressions of eNOS and α-SMA in aortic tissue significantly increased. Furthermore, the content of nitric oxide (NO) in the SHR\'s aortic tissue increased significantly. These findings confirm that graphene far-infrared radiation enhances microcirculation, regulates cytokines affecting vascular smooth muscle contraction, and modifies vascular morphology and smooth muscle phenotype, offering relief for primary hypertension.
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  • 文章类型: Journal Article
    深静脉血栓形成(DVT)是心血管疾病的第三大死亡原因,心脏病发作和中风后。早期诊断和干预对于有效的DVT治疗至关重要。我们旨在研究内皮素-1(ET-1)是否可以作为DVT大鼠模型的早期诊断标志物或潜在的治疗靶标。CCK8测定,侵袭试验,和流式细胞术用于检测增殖,HUVECs的迁移和凋亡,分别。ELISA法用于检测细胞上清液和大鼠血浆中的ET-1和凝血因子VII。Westernblot检测抗氧化信号蛋白。采用下腔静脉狭窄建立DVT大鼠模型。慢病毒介导的ET-1过表达对HUVECs细胞增殖和迁移的影响,细胞凋亡增加,抑制抗氧化信号通路蛋白的表达(例如,NQO1、GCLC、Nrf-2),和上调凝血因子VII。此外,ET-1的过表达进一步损害了响应H2O2处理的抗氧化信号通路蛋白。然而,慢病毒介导的ET-1敲低和BQ123(一种ET-1抑制剂),与ET-1过表达的结果相反。然后我们通过下腔静脉狭窄建立了DVT大鼠模型。狭窄在第1天诱导血浆中ET-1和凝血因子VII的早期表达,并在第10天恢复其水平。BQ123可以下调凝血因子VII以改善狭窄效应。我们的发现表明,ET-1可能作为DVT大鼠模型的早期诊断标志物和治疗DVT的潜在治疗靶标。
    Deep venous thrombosis (DVT) is the third leading cause of death in cardiovascular disease, following heart attacks and strokes. Early diagnosis and intervention are crucial for effective DVT therapy. We aim to investigate whether endothelin-1 (ET-1) could serve as an early diagnostic marker or a potential therapeutic target in a DVT rat model. CCK8 assay, invasion assay, and flow cytometry were used to detect the proliferation, migration and apoptosis of HUVECs, respectively. Elisa assay was used to detect ET-1 and coagulation factor VII in cell supernatant and rat?s plasma. Western blot was used to detect antioxidant signaling protein. Inferior vena cava stenosis was used to construct the DVT rat model. Lentivirus mediated overexpression of ET-1 in HUVECs impaired the cell proliferation and migration, increased cell apoptosis, inhibited the antioxidant signaling pathway proteins expression (e.g., NQO1, GCLC, Nrf-2), and upregulated coagulation factor VII. Furthermore, overexpression of ET-1 further impaired antioxidant signaling pathway protein in response to H2O2 treatment. However, lentivirus mediated ET-1 knockdown and BQ123 (an ET-1 inhibitor), showed the opposite results with ET-1 overexpression. We then established a DVT rat model by inferior vena cava stenosis. The stenosis induced early expression of ET-1 and coagulation factor VII in plasma at day 1 and restore their level at day 10. BQ123 could downregulate the coagulation factor VII to ameliorate the stenosis effects. Our findings suggest that ET-1 might serve as an early diagnostic marker for DVT rat model and a potential therapeutic target for treating DVT.
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  • 文章类型: Journal Article
    目的:特发性限制性心肌病(RCM)的发病率较低。本研究旨在确定大内皮素-1(ET-1)在特发性RCM中的预后价值。
    方法:我们前瞻性招募了2009年至2017年特发性RCM患者,并对其进行了随访。主要结局是全因死亡率和心脏移植的复合结果,次要结局是心脏死亡和心脏移植的复合结局.
    结果:91例患者分为高ET-1(>0.85pmol/L,n=56)和低的大ET-1(≤0.85pmol/L,n=35)组,其中87人完成了后续工作。大ET-1浓度(风险比:1.756,95%置信区间[CI]:1.117-2.760)和晚期钆增强(LGE)(风险比:3.851,95%CI:1.238-11.981)是主要结局的独立危险因素。大ET-1浓度(C统计量估计:0.764,95%CI:0.657-0.871)以及LGE和大ET-1浓度的组合(C统计量估计:0.870,95%CI:0.769-0.970)可以准确预测5年无移植生存率,0.85pmol/L是大ET-1的合适截止值。
    结论:BigET-1及其与LGE的联合应用可能有助于预测特发性RCM患者的不良预后。
    OBJECTIVE: Idiopathic restrictive cardiomyopathy (RCM) has a low incidence. This study aimed to determine the prognostic value of big endothelin-1 (ET-1) in idiopathic RCM.
    METHODS: We prospectively enrolled patients with idiopathic RCM from 2009 to 2017 and followed them up. The primary outcome was a composite of all-cause mortality and cardiac transplantation, and the secondary outcome was a composite of cardiac death and cardiac transplantation.
    RESULTS: Ninety-one patients were divided into the high big ET-1 (>0.85 pmol/L, n = 56) and low big ET-1 (≤0.85 pmol/L, n = 35) groups, and 87 of them completed the follow-up. Big ET-1 concentrations (hazard ratio: 1.756, 95 % confidence interval [CI]: 1.117-2.760) and late gadolinium enhancement (LGE) (hazard ratio: 3.851, 95 % CI: 1.238-11.981) were independent risk factors for the primary outcome. Big ET-1 concentrations (C-statistic estimation: 0.764, 95 % CI: 0.657-0.871) and the combination of LGE and big ET-1 concentrations (C-statistic estimation: 0.870, 95 % CI: 0.769-0.970) could accurately predict the 5-year transplant-free survival rate, and 0.85 pmol/L was a suitable cutoff for big ET-1.
    CONCLUSIONS: Big ET-1 and its combination with LGE may be useful to predict an adverse prognosis in patients with idiopathic RCM.
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  • 文章类型: Journal Article
    内皮功能紊乱是高血压发生的关键因素,关于运动对改善高血压患者内皮功能的影响仍存在争议。作者采用meta分析评价运动对高血压患者内皮功能的干预效果,并探讨可能具有更大干预效果的运动方案。共包括37项研究和2801名参与者。结果如下:内源性一氧化氮(NO)[SMD=.89,95%CI(.48,1.30),p<.0001],内皮素-1(ET-1):[SMD=-.94,95%CI(-1.15,-.73),p<.0001],流动介导的扩张(FMD)[SMD=-.57,95%CI(.36,.79),p<.000001]。在亚组分析中,高强度有氧运动,单次锻炼时间为35-50分钟,3-4次/周,共10-12周,对NO的干预作用最大,中等强度的抵抗运动,单次运动时间≥60分钟,6次/周,共15-18周,对ET-1的干预作用最大。总之,锻炼可以提高NO水平,FDM级别,降低高血压患者ET-1的分泌,从而改善其内皮功能。采用单次运动时间为35~50min的高强度有氧运动的运动处方,更有可能获得理想的改善NO水平的干预效果。3~4次/周,持续10~12周;采用单次运动时间≥60min的强度抗阻运动的运动处方,更容易获得理想的改善ET-1的干预效果,6次/周,持续15-18周。
    Endothelial dysfunction is crucial factor to the hypertension occurrence, and controversy remains regarding the effect of exercise on improving endothelial function in hypertensive patients. The authors used meta-analysis to evaluate the intervention effect of exercise on endothelial function in hypertensive patients and to investigate exercise protocols that may have a greater intervention effect. A total of 37 studies and a total of 2801 participants were included. The results were as follows: endogenous nitric oxide (NO)[SMD = .89, 95% CI (.48, 1.30), p < .0001], endothelin-1 (ET-1): [SMD = -.94, 95% CI (-1.15, -.73), p <. 0001], flow-mediated dilation (FMD) [SMD = -.57, 95% CI (.36, .79), p < .000001]. In subgroup analysis, high-intensity aerobic exercise, with a single exercise duration of 35-50 min, 3-4 times/week for a total of 10-12 weeks, had the largest amount of intervention effect on NO, and moderate-intensity resistance exercise, with a single exercise duration of ≥60 min, 6 times/week for a total of 15-18 weeks, had the largest amount of intervention effect on ET-1. In conclusion, exercise can improve NO levels, FDM levels, and reduce ET-1 secretion of hypertension patients, thereby improve their endothelial function. The ideal intervention effect of improving NO level was more likely to be obtained by taking the exercise prescription of high-intensity aerobic exercise with a single exercise duration of 35-50 min, 3-4 times/week for 10-12 weeks; the ideal intervention effect of improving ET-1 was more likely to be obtained by taking the exercise prescription of oderate -intensity resistance exercise with a single exercise duration of ≥60 min, 6 times/week for 15-18 weeks.
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