Diabetic mellitus

糖尿病
  • 文章类型: Journal Article
    糖尿病(DM)是以升高的血糖水平为特征的全球公共卫生问题。监测血糖水平对于有效管理糖尿病和预防并发症至关重要。然而,纵向生物标志物与糖尿病并发症发生率之间的关联常常被忽视.因此,这项研究旨在评估糖尿病视网膜病变的发生率,预测因子,与埃塞俄比亚糖尿病患者的纵向空腹血糖水平变化有关。
    在阿姆哈拉地区的转诊医院进行了一项多中心回顾性随访研究,埃塞俄比亚。随机抽取462例新诊断DM患者。对生存子模型的比例风险假设进行了检查,对于纵向子模型,正态假设被检查。然后拟合了具有时间相关滞后参数化的关节模型。对模型假设和比较进行了检查。最后,使用具有95%置信区间(CI)且相应P值<0.05的风险比确定预测因子.
    在这项研究中,总的来说,54例患者出现DR,在随访期间,发病率为2.33/1000人-月,95%CI为[1.78,3.05]。农村住宅(AHR=2.21,95%CI:[1.21,4.05]),高血压合并症(AHR=3.01,95%CI:[1.85,6.53]),DM持续时间较长(>5年)(AHR=2.28,95%CI:[1.91,5.15])是DR发病率的重要预测因子。此外,DR的发生率与FBS变化的时间依赖性滞后值显著相关(AHR=4.20,95%CI[1.62,10.85]).
    在这项研究中,与之前在埃塞俄比亚开展的类似研究相比,糖尿病性视网膜病变的发病率较高.纵向空腹血糖水平变化的联合模型与DR风险增加显着相关。此外,作为农村住宅,高血压合并症,DM持续时间较长是DR发病率的重要预测因素。因此,公众意识,综合护理方法,强烈建议优先控制血糖.
    UNASSIGNED: Diabetes mellitus (DM) is a global public health problem characterized by an elevated blood glucose level. Monitoring blood sugar levels is vital for effective diabetes management and preventing complications. However, the association between longitudinal biomarkers and the incidence of diabetic complications is often overlooked. Therefore, this study aimed to assess the incidence of diabetic retinopathy, predictors, and association with longitudinal fasting blood sugar level changes among diabetes mellitus patients in Ethiopia.
    UNASSIGNED: A multicenter retrospective follow-up study was carried out in referral hospitals in Amhara region, Ethiopia. A random sample of 462 newly diagnosed DM patients was selected. The proportional hazard assumption was checked for the survival sub-model, and for the longitudinal sub-model, the normality assumption was checked. Then the joint modeling with time-dependent lagged parameterizations was fitted. Model assumptions and comparisons were checked. Finally, the hazard ratio with a 95% confidence interval (CI) with a corresponding P-value<0.05 was used to identify predictors.
    UNASSIGNED: In this study, Overall, 54 patients developed DR, and the incidence rate was 2.33 per 1000 person-months over the follow-up period, with a 95% CI of [1.78, 3.05]. Rural residence (AHR = 2.21, 95% CI: [1.21, 4.05]), hypertension co-morbidity (AHR = 3.01, 95% CI: [1.85, 6.53]), and longer duration of DM (>5 years) (AHR = 2.28, 95% CI: [1.91, 5.15]) were important predictors for the incidence of DR. In addition, the incidence of DR was substantially correlated with the time-dependent lagged value of FBS change (AHR = 4.20, 95% CI [1.62, 10.85]).
    UNASSIGNED: In this study, the incidence of diabetic retinopathy was somewhat high when compared to prior similar studies in Ethiopia. A joint model of longitudinal fasting blood sugar level changes was significantly associated with an increased risk of DR. Besides, being rural residence, hypertension co-morbidity, and a longer duration of DM were significant predictors for the incidence of DR. Therefore, public awareness, an integrated care approach, and prioritizing glycemic control are highly recommended.
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  • 文章类型: Journal Article
    糖尿病是一种多系统表现的常见病,在全球范围内造成严重的残疾和死亡负担。血管紧张素受体脑啡肽抑制剂(ARNI)属于一类治疗心力衰竭的药物,具有降低住院率和死亡率的益处。这篇综述主要集中在与ARNI和糖尿病并发症相关的临床和基础研究。讨论可能的生理和分子机制,对未来应用的见解。
    Diabetes mellitus is a prevalent disorder with multi-system manifestations, causing a significant burden in terms of disability and deaths globally. Angio-tensin receptor-neprilysin inhibitor (ARNI) belongs to a class of medications for treating heart failure, with the benefits of reducing hospitalization rates and mortality. This review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications, discussing possible physiological and molecular mechanisms, with insights for future applications.
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  • 文章类型: Journal Article
    糖尿病(DM)是一组以胰岛素分泌缺陷导致的高血糖为特征的代谢性疾病。胰岛素作用,或者两者兼而有之。该研究旨在评估口腔健康教育和干预在改善2型糖尿病(T2DM)患者口腔健康结局中的有效性。方法本研究于2023年2月至2023年8月在钦奈的Saveetha牙科学院和医院的口腔医学和放射科进行,印度。研究中的所有患者均患有2型糖尿病并伴有口腔表现。这项研究招募了105名参与者,其中女性63人,男性42人。向所有参与者提供了标准的形式,并记录了调查结果。形式包括不同的口腔表现,血糖水平,腐烂的,失踪,和填充牙齿(DMFT)指数,和Russell的牙周指数.然后对结果进行统计分析。结果这项对105名T2DM患者(60%的女性和40%的男性)的研究揭示了显着的口腔健康挑战:33%患有牙周炎,20%有牙龈炎,5%有苔藓样反应,23%有口干症,11%有口臭,8%有念珠菌病,说明糖尿病对牙齿健康的影响。在适当的情况下,为个别患者量身定制的治疗方法,例如缩放,根规划,口腔卫生教育,药物治疗,和干预后,并发症的发生率显著下降了61%。共有7%的患者有牙龈炎,11%有牙周炎,12%有口干症,4%有口臭,2%有念珠菌病,1%有苔藓样反应,分别。这突出了定期口腔护理对糖尿病患者产生积极影响的重要性。61%的人口腔健康得到改善,39%的人没有改善。结论本研究为口腔健康教育和干预措施在改善T2DM患者口腔健康结局方面的有效性提供了有力的证据。这种方法为管理与糖尿病相关的口腔健康并发症和改善该人群的整体健康和福祉提供了一个有前途的策略。
    Introduction Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The study aimed to evaluate the effectiveness of oral health education and intervention in improving oral health outcomes in type 2 DM (T2DM) patients. Methods The present study was conducted in the Department of Oral Medicine and Radiology between February 2023 and August 2023 at Saveetha Dental College and Hospitals in Chennai, India. All of the patients in the study had T2DM with oral manifestations. This study enrolled 105 participants, of whom 63 were female and 42 were male. A standard pro forma was given to all the participants, and the findings were recorded. The pro forma comprises different oral manifestations, blood glucose levels, the Decayed, Missing, and Filled Teeth (DMFT) index, and Russell\'s periodontal index. The results were then statistically analyzed. Results This study of 105 individuals with T2DM (60% females and 40% males) revealed significant oral health challenges: 33% had periodontitis, 20% had gingivitis, 5% had lichenoid reactions, 23% had xerostomia, 11% had halitosis, and 8% had candidiasis, illustrating diabetes\' impact on dental health. Following appropriate, tailor-made treatment for individual patients, such as scaling, root planning, oral hygiene education, pharmacotherapy, and post-intervention, the prevalence of complications notably decreased by 61%. A total of 7% of patients had gingivitis, 11% had periodontitis, 12% had xerostomia, 4% had halitosis, 2% had candidiasis, and 1% had lichenoid reactions, respectively. This highlights the importance of regular oral care positively impacting diabetes patients, with 61% experiencing improved oral health and 39% experiencing no improvement. Conclusion This study provides compelling evidence for the effectiveness of oral health education and interventions in improving oral health outcomes in T2DM patients. This approach offers a promising strategy for managing the oral health complications associated with diabetes and improving this population\'s overall health and well-being.
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  • 文章类型: Journal Article
    糖尿病肾病是一种进行性疾病和终末期肾病的主要原因。氧化应激和炎症在其发病机制中起重要作用。在临床前研究中,孟鲁司特已显示出肾脏保护和抗氧化特性,因此,本研究计划评估孟鲁司特在链脲佐菌素(STZ)诱导的糖尿病肾病模型中的作用.
    40只Wistar大鼠随机分为四组。1.车辆控制组,2.依那普利(5mg/kg),3.孟鲁司特低剂量(10mg/kg)和4。高剂量(20mg/kg)组。在第1天,使用单剂量的STZ(60mg/kg)腹膜内诱导糖尿病。基于第7天和第8天至第42天的空腹血糖(FBG)水平验证糖尿病诱导,给予大鼠研究药物。FBG,血清肌酐,在研究前和研究后评估血尿素氮(BUN)和尿微量白蛋白水平.肾脏丙二醛(MDA)的评估,在研究结束时进行了还原型谷胱甘肽(GSH)和肾组织病理学检查.
    孟鲁司特10mg/kg组显示与载体对照组相比显著更低的尿微量白蛋白水平(p<0.05)。孟鲁司特20mg/kg组FBG水平明显降低,血清肌酐,BUN和尿微量白蛋白与载体对照组相比(p<0.05)。此外,与媒介物对照组相比,孟鲁司特20mg/kg组还对肾脏MDA和GSH水平(p<0.05)和组织病理学评分显示出更好的效果。
    孟鲁司特因其抗氧化作用而在糖尿病肾病模型中显示出保护作用。
    UNASSIGNED: Diabetic nephropathy is a progressive condition and a leading cause of end-stage renal disease. Oxidative stress and inflammation play an important role in its pathogenesis. In pre-clinical studies, Montelukast had shown renoprotective and anti-oxidant properties, hence the study was planned to evaluate the effect of Montelukast in a Streptozotocin (STZ) induced model of diabetic nephropathy.
    UNASSIGNED: 40 Wistar rats of either sex were randomly divided into four groups viz. 1. Vehicle control group, 2. Enalapril (5 mg/kg), 3. Montelukast low-dose (10 mg/kg) and 4. High-dose (20 mg/kg) group. On day 1, diabetes was induced using a single dose of STZ (60 mg/kg) intraperitoneally. Diabetes induction was verified based on fasting blood glucose (FBG) levels on day 7 and from day 8 to day 42, rats were given study drugs. FBG, serum creatinine, blood urea nitrogen (BUN) and urine microalbumin levels were assessed pre-study and post-study. Assessments of kidney malondialdehyde (MDA), reduced glutathione (GSH) and renal histopathology were carried out at the end of the study.
    UNASSIGNED: Montelukast 10 mg/kg group showed significantly lower urine microalbumin levels compared to the vehicle control group (p < 0.05). Montelukast 20 mg/kg group showed significantly lower levels of FBG, serum creatinine, BUN and urine microalbumin compared to the vehicle control group (p < 0.05). In addition, Montelukast 20 mg/kg group also showed better effects on kidney MDA and GSH levels (p < 0.05) and histopathological scores compared to the vehicle control group.
    UNASSIGNED: Montelukast showed a protective effect in the model of diabetic nephropathy because of its antioxidant effect.
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  • 文章类型: Journal Article
    颈动脉粥样硬化是缺血性卒中的主要原因,缺血性中风是全球发病率和死亡率的主要原因。不幸的是,动脉粥样硬化斑块形成的原因尚不清楚.miRNA-29c可促进糖尿病小鼠血管平滑肌细胞(VSMCs)的表型转化,最终导致斑块形成和出血。然而,这种研究很少见,仅限于动物实验。
    在我们的研究中,根据是否诊断为DM,将40例患者分为糖尿病(DM)组和非DM组。然后,应用实时定量PCR检测来自40例接受颈动脉内膜切除术的受试者的人颈动脉斑块组织中的miRNA-29c水平.
    简而言之,与非DM受试者相比,糖尿病患者的miRNA-29c水平降低,这种比较具有统计学意义(P=0.02)。值得注意的是,可变miRNA-29c水平与HbA1c水平呈负相关,尽管没有观察到统计学意义。此外,卒中患者的miRNA-29c水平升高.
    集体,颈动脉斑块中miRNA-29c水平与DM和脑卒中密切相关,这可能有助于动脉粥样硬化的形成。
    UNASSIGNED: Carotid artery atherosclerosis is a major cause of ischemic stroke, and ischemic stroke is the leading cause of morbidity and mortality worldwide. Unfortunately, the reason for the build-up of atherosclerosis plaque is unknown. The miRNA-29c was reported to promote the phenotype transformation of vascular smooth muscle cells (VSMCs) in diabetes mice, eventually leading to plaque formation and bleeding. However, such studies are rare and limited to animal experiments.
    UNASSIGNED: In our study, 40 patients were divided into a diabetic mellitus (DM) group and a non-DM group according to whether they were diagnosed with DM. Then, the real-time quantitative PCR was applied to examine the miRNA-29c level in human carotid plaque tissue derived from 40 subjects receiving carotid endarterectomy.
    UNASSIGNED: Briefly, diabetes patients had a decreased miRNA-29c level as compared with non-DM subjects, and this comparison was statistically significant (P = 0.02). Notably, variable miRNA-29c level was negatively associated with HbA1c level, although no statistical significance was observed. Moreover, there was an increased miRNA-29c level in patients with cerebral stroke.
    UNASSIGNED: Collectively, the miRNA-29c level in the carotid plaque is closely associated with DM and cerebral stroke, which may contribute to atherosclerosis formation.
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  • 文章类型: Journal Article
    背景:非传染性疾病是生活方式疾病,在全世界范围内都在增加。他们造成了全世界71%的死亡,其中1600万人过早死亡或在70岁之前死亡。在非传染性疾病中,糖尿病和高血压是最常见的。该研究旨在发现糖尿病和高血压患者中抑郁症的患病率。
    方法:对370名被诊断为糖尿病的受试者进行了描述性横断面研究,高血压,都在Mangaluru的K.SHegde慈善医院。采用有目的的抽样技术来选择受试者。患者健康问卷-9(PHQ-9)用于查找客户中的抑郁症状。统计分析使用SPSS版本20(Armonk,纽约:IBM公司);使用描述性(频率和百分比)和推断性(单向方差分析(ANOVA))统计来解释数据。
    结果:在370名受试者中,41%没有抑郁症,大多数59%患有轻度至重度抑郁症。在诊断为糖尿病的客户中(n=139),大多数(63%)患有轻度至重度抑郁症.同样,被诊断为高血压的受试者,51%没有抑郁症,49%患有轻度至重度抑郁症。此外,在被诊断患有糖尿病和高血压的受试者中(n=99),67%患有轻度至重度抑郁症。
    结论:研究表明,许多在医院门诊就诊的糖尿病和高血压患者会出现抑郁。所以,早期识别抑郁症状并采取适当措施预防并发症至关重要。
    BACKGROUND: Non-communicable diseases are lifestyle diseases that are increasing throughout the world. They are responsible for 71% of death worldwide, among which 16 million people die prematurely or before reaching the age of 70 years. Among the non-communicable diseases, diabetes and hypertension are the most common. The study aimed to find the prevalence of depression among diabetes and hypertensive clients.
    METHODS: A descriptive cross-sectional study was conducted among 370 subjects diagnosed with diabetes mellitus, hypertension, and both in Justice K.S Hegde Charitable Hospital at Mangaluru. A purposive sampling technique was adopted to select the subjects. Patient health questionnaire-9 (PHQ-9) was used to find the depressive symptoms among the client. The statistical analysis was conducted using SPSS version 20 (Armonk, NY: IBM Corp.); descriptive (frequency and percentage) and inferential (one-way analysis of variance (ANOVA)) statistics were used to interpret the data.
    RESULTS: Out of 370 subjects, 41% had no depression, and most 59% had mild to severe levels of depression. Among clients diagnosed with diabetes mellitus (n = 139), the majority (63%) had mild to severe depression. Similarly, of subjects diagnosed with hypertension, 51% had no depression, and 49% had mild to severe depression. In addition, among subjects diagnosed with both diabetes mellitus and hypertension (n = 99), 67% had mild to severe depression.
    CONCLUSIONS: The study shows that many diabetes and hypertensive patients attending the outpatient departments of the hospital experience depression. So, it is crucial to identify the depressive symptoms early and take appropriate measures to prevent complications.
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  • 文章类型: Journal Article
    背景:Wolfram综合征(WS)是一种罕见的常染色体隐性遗传多系统神经退行性疾病,其特征是非自身免疫性胰岛素依赖型糖尿病,视神经萎缩,感觉神经性耳聋,以糖尿病为主要特征。由于临床表型异质性,误诊率高。然而,早期准确诊断和综合管理是提高生活质量和延长寿命的关键。
    结果:来自7个WS家系的11名患者,具有10个突变位点(c.1314_1317delCTTT,c.C529T,c.C529A,c.G2105A,c.C1885T,c.1859_1860del,c.G2020A,c.C529A,c.G2105A,包括WFS1基因中的c.G1393C)。我们进行了进一步的专家部门分析,以明确诊断并分析基因与表型之间的相关性。
    结论:这些患者的基因型与其表型密切相关。分析患者的临床资料,为该病的诊断和临床管理提供依据。
    BACKGROUND: Wolfram syndrome (WS) is a rare autosomal recessive multisystem neurodegenerative disease characterized by non-autoimmune insulin-dependent diabetes mellitus, optic atrophy, sensorineural deafness, and diabetes as the main features. Owing to clinical phenotypic heterogeneity, the misdiagnosis rate is high. However, early accurate diagnosis and comprehensive management are key to improving quality of life and prolonging life.
    RESULTS: Eleven patients from seven WS pedigrees with 10 mutation sites (c.1314_1317delCTTT, c.C529T, c.C529A, c.G2105A, c.C1885T, c.1859_1860del, c.G2020A, c.C529A, c.G2105A, and c.G1393C) in the WFS1 gene were included. We conducted further expert department analysis to clarify the diagnosis and analyze the correlation between genes and phenotypes.
    CONCLUSIONS: The genotypes of these patients were closely associated with their phenotypes. The clinical data of the patients were analyzed to provide a basis for the diagnosis and clinical management of the disease.
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  • 文章类型: Journal Article
    背景:糖尿病被广泛认为是全球最紧迫的公共卫生问题之一。管理血糖水平,减少后续并发症和死亡率,已经发现自我管理机制在控制糖尿病方面是有效的。本研究旨在探讨Qazvin地区1型糖尿病患者精神智力与糖尿病自我管理的关系,伊朗。
    方法:这项横断面研究包括220名18-35岁的1型糖尿病成年人,他们转诊到Qazvin省三级医院的门诊糖尿病诊所,并于2022年通过便利抽样方法进行了选择。使用两份有效可靠的问卷进行数据收集,包括24项青少年1型糖尿病精神智力和自我管理问卷(SMOD-A)。为了分析数据,相关系数和多元线性回归分析。
    结果:精神智力总分为57.24±10.77,自我管理总分为77.14±8.92。在精神智力的不同分量中,批判性思维获得了最高分。在自我管理中,沟通得分最高。研究还显示,精神智力可以预测糖尿病患者自我管理变化的7.2%,其与糖尿病自我管理的关系估计为0.27。
    结论:全球范围内糖尿病患病率的增长强调了疾病自我管理对患者健康的重要性。这项研究表明,精神智力在患有糖尿病的年轻人中起着至关重要的作用,并帮助他们应对压力。因此,必须更加重视精神方面的护理,特别是在治疗糖尿病及其复杂疾病的年轻人的医疗保健方面。
    BACKGROUND: Diabetes is widely recognized as one of the most pressing public health concerns globally. To manage blood glucose levels and reduce subsequent complications and mortality rates, self-management mechanisms have been found to be effective in controlling diabetes. This study aimed to investigate the association between spiritual intelligence and diabetes self-management in patients with type 1 diabetes in Qazvin, Iran.
    METHODS: This cross-sectional study included 220 adults with type 1 diabetes aged 18-35 years who referred to an outpatient diabetes clinic of a tertiary hospital in Qazvin province, and were selected through a convenience sampling method in 2022. Two valid and reliable questionnaires were used for data collection, including the 24-item questionnaire of spiritual intelligence and self-management of type 1 diabetes for adolescents (SMOD-A). To analyze the data, correlation coefficients and multiple linear regression analysis were used.
    RESULTS: The total score of spiritual intelligence was 57.24 ± 10.77, and self-management was 77.14 ± 8.92. Among different subscales of spiritual intelligence, critical thinking obtained the highest score. In self-management, the highest score was achieved for communication.Findings also revealed that spiritual intelligence could predict 7.2% of changes in self-management among diabetes patients, and its relationship with diabetes self-management was estimated at 0.27.
    CONCLUSIONS: The growing prevalence of diabetes worldwide underscores the significance of self-management of the disease in the well-being of patients. This study demonstrated that spiritual intelligence played a crucial role among young adults with diabetes and assisted them in coping with stressful situations. As such, placing greater emphasis on the spiritual aspects of care is necessary, especially in the healthcare of young adults who are dealing with diabetes and its complex conditions.
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  • 文章类型: Journal Article
    糖尿病伤口被认为是糖尿病最常见和最严重的并发症之一。最近,由于其组织修复特性,网膜已用于糖尿病伤口愈合。活化的网膜比失活的网膜富含生长因子,从而有助于伤口愈合过程。进一步探讨活化大网膜条件培养液(aOCM)对糖尿病创面愈合的影响,我们从aOCM中注入上清液,盐水-OCM(sOCM),灭活OCM(iOCM),在糖尿病小鼠中创建皮肤伤口愈合模型后皮下培养基(M)。在手术后第0、3、5、7、9、11、14、21和28天评估伤口面积(%)。术后9天和28天,采集皮肤组织并进行粗略观察,新生血管形成,周围神经纤维再生,和胶原蛋白沉积。我们观察到aOCM增强了伤口修复过程,在第9天,手术部位的表皮和胶原蛋白沉积显着加速。此外,aOCM在伤口愈合期间显示了新血管形成和外周神经再生的显著效率。因此,aOCM管理对糖尿病小鼠模型产生积极影响,可用作糖尿病伤口的新疗法。
    Diabetic wounds are considered one of the most frequent and severe complications of diabetes mellitus. Recently, the omentum has been used in diabetic wound healing because of its tissue repair properties. The activated omentum is richer in growth factors than the inactivated, thereby contributing to the wound healing process. To further investigate the effect of activated omentum conditioned medium (aOCM) on diabetic wound healing, we injected supernatant from aOCM, saline-OCM (sOCM), inactivated-OCM (iOCM), and medium (M) subcutaneously upon creation of a cutaneous wound healing model in diabetic mice. Wound area (%) was evaluated on days 0, 3, 5, 7, 9, 11, 14, 21, and 28 post-operation. At 9 and 28 d post-operation, skin tissue was harvested and assessed for gross observation, neovascularization, peripheral nerve fiber regeneration, and collagen deposition. We observed that aOCM enhanced the wound repair process, with significant acceleration of epidermal and collagen deposition in the surgical lesion on day 9. Additionally, aOCM displayed marked efficiency in neovascularization and peripheral nerve regeneration during wound healing. Thus, aOCM administration exerts a positive influence on the diabetic mouse model, which can be employed as a new therapy for diabetic wounds.
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  • 文章类型: Journal Article
    目的:探讨自噬抑制剂3-甲基腺嘌呤(3-MA)在糖尿病小鼠模型中的作用及其机制。
    方法:雄性C57BL/6J小鼠随机分为正常对照组(NC组)和DM组。连续5天多次小剂量腹腔注射链脲佐菌素(STZ)60mg/kg·d诱导DM。将DM小鼠随机分为未治疗组(DM组),3-MA(灌胃10mg/kg·d)治疗组(DM3-MA组)和氯喹(CQ;腹腔注射50mg/kg)治疗组(DMCQ组)。每周记录空腹血糖(FBG)水平。实验结束时,收集视网膜样本。促凋亡蛋白裂解的caspase-3,裂解的聚ADP-核糖聚合酶1(PARP1)和Bax的表达水平,抗凋亡蛋白Bcl-2,纤维化相关蛋白纤连蛋白和1型胶原α1链(COL1A1),血管内皮生长因子(VEGF),炎症因子白细胞介素(IL)-1β和肿瘤坏死因子(TNF)-α,以及自噬相关蛋白LC3,Beclin-1和P62通过蛋白质印迹法测定。通过商业试剂盒检测氧化应激指标8-羟基脱氧鸟苷(8-OHdG)和丙二醛(MDA)。
    结果:3-MA和CQ均对DM小鼠FBG有短期降血糖作用,并降低VEGF和炎症因子IL-1β和TNF-α的表达。3-MA还显著缓解氧化应激指标8-OHdG和MDA,降低纤维化相关蛋白纤连蛋白和COL1A1的表达,促凋亡蛋白裂解的caspase-3,裂解的PARP1以及Bax/Bcl-2的比例。CQ对氧化应激指标无显著影响,纤维化,和凋亡相关蛋白。自噬相关蛋白的Westernblotting结果显示,3-MA治疗可降低DM小鼠视网膜中LC3Ⅱ/LC3Ⅰ的比值和Beclin-1的表达,通过CQ处理,P62的表达进一步增加。
    结论:3-MA对DM小鼠视网膜具有抗凋亡和抗纤维化作用,并能减弱视网膜氧化应激,DM小鼠视网膜VEGF表达与炎症因子的产生。3-MA的上述作用机制可能与其抑制早期自噬和降血糖作用有关。
    OBJECTIVE: To investigate the role of autophagy inhibitor 3-methyladenine (3-MA) on a diabetic mice model (DM) and the potential mechanism.
    METHODS: Male C57BL/6J mice were randomly divided into a normal control group (NC group) and an DM group. DM were induced by multiple low-dose intraperitoneal injection of streptozotocin (STZ) 60 mg/kg·d for 5 consecutive days. DM mice were randomly subdivided into untreated group (DM group), 3-MA (10 mg/kg·d by gavage) treated group (DM+3-MA group) and chloroquine (CQ; 50 mg/kg by intraperitoneal injection) treated group (DM+CQ group). The fasting blood glucose (FBG) levels were recorded every week. At the end of experiment, retinal samples were collected. The expression levels of pro-apoptotic proteins cleaved caspase-3, cleaved poly ADP-ribose polymerase 1 (PARP1) and Bax, anti-apoptotic protein Bcl-2, fibrosis-associated proteins Fibronectin and type 1 collagen α1 chain (COL1A1), vascular endothelial growth factor (VEGF), inflammatory factors interleukin (IL)-1β and tumor necrosis factor (TNF)-α, as well as autophagy related proteins LC3, Beclin-1 and P62 were determined by Western blotting. The oxidative stress indicators 8-hydroxydeoxyguanosine (8-OHdG) and malondialdehyde (MDA) were detected by commercial kits.
    RESULTS: Both 3-MA and CQ had short-term hypoglycemic effect on FBG and reduced the expression of VEGF and inflammatory factors IL-1β and TNF-α in DM mice. 3-MA also significantly alleviated oxidative stress indicators 8-OHdG and MDA, decreased the expression of fibrosis-related proteins Fibronectin and COL1A1, pro-apoptotic proteins cleaved caspase-3, cleaved PARP1, as well as the ratio of Bax/Bcl-2. CQ had no significant impact on the oxidative stress indicators, fibrosis, and apoptosis related proteins. The results of Western blotting for autophagy related proteins showed that the ratio of LC3 II/LC3 I and the expression of Beclin-1 in the retina of DM mice were decreased by 3-MA treatment, and the expression of P62 was further increased by CQ treatment.
    CONCLUSIONS: 3-MA has anti-apoptotic and anti-fibrotic effects on the retina of DM mice, and can attenuate retinal oxidative stress, VEGF expression and the production of inflammatory factors in the retina of DM mice. The underlying mechanism of the above effects of 3-MA may be related to its inhibition of early autophagy and hypoglycemic effect.
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