关键词: 3’, 4′-dihydroxyflavonol AQP4 Apoptosis Brain ischemia IL-10

Mesh : Animals Male Reperfusion Injury / drug therapy pathology metabolism Flavonols / pharmacology therapeutic use Rats, Wistar Rats Cognition / drug effects Caspase 3 / metabolism Aquaporin 4 / metabolism Interleukin-10 / metabolism Neuroprotective Agents / pharmacology therapeutic use Hippocampus / drug effects metabolism pathology Neurons / drug effects pathology metabolism Brain Ischemia / drug therapy metabolism Disease Models, Animal Apoptosis / drug effects

来  源:   DOI:10.1016/j.ejphar.2024.176670

Abstract:
BACKGROUND: Ischemia/reperfusion is a pathological condition by the restoration of perfusion and oxygenation following a period of restricted blood flow to an organ. To address existing uncertainty in the literature regarding the effects of 3\', 4\'-dihydroxy flavonol (DiOHF) on cerebral ischemia/reperfusion injury, our study aims to investigate the impact of DiOHF on neurological parameters, apoptosis (Caspase-3), aquaporin 4 (AQP4), and interleukin-10 (IL-10) levels in an experimental rat model of brain ischemia-reperfusion injury.
METHODS: A total of 28 Wistar-albino male rats were used in this study. Experimental groups were formed as 1-Control, 2-Sham, 3-Ischemia-reperfusion, 4-Ischemia-reperfusion + DiOHF (10 mg/kg). The animals were anaesthetized, and the carotid arteries were ligated (ischemia) for 30 min, followed by reperfusion for 30 min. Following reperfusion, DiOHF was administered intraperitoneally to the animals at a dose of 10 mg/kg for 1 week. During the one-week period neurological scores and new object recognition tests were performed. Then, caspase 3 and AQP4 levels were determined by PCR method and IL-10 by ELISA method in hippocampus tissue samples taken from animals sacrificed under anaesthesia.
RESULTS: Brain ischemia reperfusion significantly increased both caspase 3 and AQP4 values in the hippocampus tissue, while decreasing IL-10 levels. However, 1-week DiOHF supplementation significantly suppressed increased caspase 3 and AQP4 levels and increased IL-10 values. While I/R also increased neurological score values, it suppressed the ability to recognize new objects, and the administered treatment effectively ameliorated the adverse effects observed, resulting in a positive outcome.
CONCLUSIONS: The results of the study show that brain ischemia caused by bilateral carotid occlusion in rats and subsequent reperfusion causes tissue damage, but 1-week DiOHF application has a healing effect on both hippocampus tissue and neurological parameters.
摘要:
背景:缺血/再灌注是在一段有限的血液流向器官后恢复灌注和氧合的病理状况。为了解决文献中关于3\'的影响的现有不确定性,4\'-二羟基黄酮醇(DiOHF)对脑缺血/再灌注损伤,我们的研究旨在探讨DiOHF对神经参数的影响,凋亡(Caspase-3),水通道蛋白4(AQP4),和白细胞介素-10(IL-10)水平在实验性大鼠脑缺血再灌注损伤模型中的作用。
方法:本研究使用了28只Wistar白化病雄性大鼠。实验组作为1-对照,2-Sham,3-缺血再灌注,4-缺血-再灌注+DiOHF(10mg/kg)。动物被麻醉,颈动脉结扎(缺血)30分钟,然后再灌注30分钟。再灌注后,将DiOHF以10mg/kg的剂量腹膜内给予动物1周。在一周的时间内,进行了神经系统评分和新的物体识别测试。然后,用PCR方法测定海马组织中的caspase3和AQP4水平,用ELISA方法测定IL-10。
结果:脑缺血再灌注显著增加海马组织的caspase3和AQP4值,同时降低IL-10水平。然而,1周的DiOHF补充显着抑制了caspase3和AQP4水平的增加,并增加了IL-10值。虽然I/R也增加了神经评分值,它抑制了识别新物体的能力,所给予的治疗有效地改善了观察到的不良反应,产生积极的结果。
结论:研究结果表明,大鼠双侧颈动脉闭塞引起的脑缺血以及随后的再灌注引起组织损伤,但1周的DiOHF应用对海马组织和神经参数都有治愈作用。
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