首页|杜鹃花总黄酮通过抑制TNF-α/caspase-8/caspase-3信号通路减轻大鼠脑缺血再灌注损伤的作用

杜鹃花总黄酮通过抑制TNF-α/caspase-8/caspase-3信号通路减轻大鼠脑缺血再灌注损伤的作用

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目的 探索杜鹃花总黄酮(TFR)通过抑制TNF-α/caspase-8/caspase-3信号通路保护脑缺血再灌注(I/R)损伤的机制。方法 采用大脑中动脉闭塞术(MCAO)建立大鼠I/R模型,将造模成功大鼠随机分为假手术(Sham)、脑缺血再灌注(MCAO)和脑缺血再灌注术后TFR 200 mg/kg干预(TFR 200 mg/kg)组,制备MCAO大鼠模型,在脑缺血再灌注损伤手术后,TFR 200 mg/kg组连续14 d给予TFR(200 mg/kg)药物溶液。术后14 d,依据大鼠神经功能评分,脑血流图观察脑血流情况,处死大鼠,苏木精-伊红(HE)染色观察脑组织细胞形态学变化,试剂盒检测大鼠血清中乳酸脱氢酶(LDH或LD)和神经特异性烯醇化酶(NSE)两种酶活性;ELISA试剂盒检测白细胞介素-1(IL-1)和IL-6水平,Western blot和免疫组化同时检测大鼠脑组织中裂解型胱天蛋白酶 3(cleaved caspase-3)、caspase-8、肿瘤坏死因子(TNF)-α蛋白的表达水平。结果 脑缺血再灌注处理后,MCAO导致了大鼠神经功能异常,神经功能评分指数显著升高,脑组织病理形态学和脑血流量变化明显,脑组织中cleaved caspase-3、caspase-8、TNF-α 蛋白的表达水平显著增加,血清中LDH、NSE、IL-1、IL-6水平明显升高;TFR 200 mg/kg组大鼠神经功能评分明显降低,脑组织病理损伤显著改善,脑组织中 cleaved caspase-3、caspase-8、TNF-α 蛋白的表达以及血清中LDH、NSE、IL-1、IL-6水平降低。结论 TFR可能通过抑制TNF-α/caspase-8/caspase-3信号通路减轻脑缺血缺氧性损伤。
The total flavonoids of rhododendron alleviate rat brain ischemia-reperfusion injury by inhibiting the TNF-α/caspase-8/caspase-3 signaling pathway
Objective To explore the mechanism by which total flavones of rhododendron(TFR)protect against cerebral ischemia-reperfusion(I/R)injury by inhibiting the TNF-α/caspase-8/caspase-3 signaling pathway.Methods The middle cerebral artery occlusion(MCAO)method was used to establish the rat I/R model.Rats were randomly divided into Sham surgery,MCAO,and post-I/R intervention with TFR 200 mg/kg(TFR 200 mg/kg)groups.After establishing the MCAO rat model,rats in the TFR 200 mg/kg group were administered TFR(200 mg/kg)solution for 14 consecutive days following I/R injury surgery.Hematoxylin-Eosin(HE)staining was used to observe neurological function scoring,cerebral blood flow assessment,histological examination of brain tis-sue,assay kits were used to detect lactate dehydrogenase(LDH)and neuron-specific enolase(NSE)activities in rat serum.ELISA assay kits was used to measure interleukin-1(IL-1)and interleukin-6(IL-6)levels,and West-ern blot and immunohistochemistry were conducted to detect the expression levels of cleaved caspase-3,caspase-8,and TNF-α proteins in rat brain tissue 14 days post-surgery.Results After cerebral ischemia-reperfusion treat-ment,MCAO resulted in abnormal neurological function in rats,significantly increased neurological function sco-ring index,obvious changes in cerebral tissue histomorphology and cerebral blood flow,significant upregulation of cleaved caspase-3,caspase-8,and TNF-α protein expression levels in brain tissue,and significant elevation of LDH,NSE,IL-1,and IL-6 levels in serum.Rats in the TFR 200 mg/kg group showed significantly reduced neu-rological function scoring,significant improvement in cerebral tissue pathological damage,decreased expression levels of cleaved caspase-3,caspase-8,and TNF-α proteins in brain tissue,as well as decreased levels of LDH,NSE,IL-1,and IL-6 in serum.Conclusion TFR may alleviate cerebral ischemic hypoxic injury by inhibiting the TNF-α/caspase-8/caspase-3 signaling pathway.

total flavones of rhododendroncerebral ischemia-reperfusioncerebral ischemic hypoxic injuryap-optosis

余孝海、金宇、孙敏琼、郭欠影、从辉

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安徽医科大学基础医学院,合肥 230032

安徽医科大学第一附属医院病理科,合肥 230022

安徽医科大学第一附属医院东城院区神经内科,合肥 231600

杜鹃花总黄酮 脑缺血再灌注 脑缺血缺氧性损伤 凋亡

安徽省高校自然科学研究项目安徽省研究生教育质量工程项目安徽医科大学国家级大学生创新创业训练计划项目

2023AH0533102022xscx053202310366037

2024

安徽医科大学学报
安徽医科大学

安徽医科大学学报

CSTPCD北大核心
影响因子:1.095
ISSN:1000-1492
年,卷(期):2024.59(6)
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