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基于PI3K/Akt通路探讨氯吡格雷对脑缺血再灌注 损伤大鼠的神经保护作用
温瑶郑文旭姜巍王玲
0
()
摘要:
目的 基于磷酯酰激醇 3- 激酶 / 蛋白激酶 B(PI3K/Akt)通路探讨氯吡格雷对脑缺血再 灌注损伤大鼠的神经保护作用。方法 建立脑缺血再灌注大鼠模型,随机分为模型组、氯吡格雷组、 LY294002(PI3K 抑制剂)组、氯吡格雷 +LY294002 组,每组 12 只,另取 12 只 SD 大鼠设为假手术组。分组 处理后,所有大鼠进行神经功能缺损评分并尾静脉取血,处死大鼠,HE 染色检测各组大鼠神经元病理 情况;三苯基氯化四氮唑(TTC)染色检测各组大鼠脑组织梗死面积;ELISA 检测血清中中枢神经特异性 蛋白(S100β)、神经元特异性烯醇化酶(NSE)、白细胞介素 -6(IL-6)、肿瘤坏死因子 -α(TNF-α)水平;蛋 白免疫印迹法检测脑组织中 PI3K/Akt 通路蛋白表达情况。结果 与假手术组相比,模型组大鼠脑组织 神经元出现坏死、核收缩变小等病理变化,神经功能缺损评分、脑梗死面积、血清中 S100β、NSE、IL-6 及 TNF-α 水平均明显升高(P< 0.05),脑组织中 p-PI3K/PI3K、p-Akt/Akt 明显降低(P< 0.05);与模型组相 比,氯吡格雷组大鼠神经元病理损伤减轻,神经功能缺损评分、脑梗死面积、血清中 S100β、NSE、IL-6 及 TNF-α 水平均降低(P< 0.05),脑组织中 p-PI3K/PI3K、p-Akt/Akt 升高(P< 0.05);LY294002 组大鼠神 经元病理损伤加重,神经功能缺损评分、脑梗死面积、血清中 S100β、NSE、IL-6 及 TNF-α水平均升高 (P< 0.05),脑组织中 p-PI3K/PI3K、p-Akt/Akt 降低(P< 0.05)。与 LY294002 组相比,氯吡格雷 +LY294002 组大鼠神经元病理损伤减轻,神经功能缺损评分、脑梗死面积、血清中 S100β、NSE、IL-6 及 TNF-α 水 平均降低(P< 0.05),脑组织中 p-PI3K/PI3K、p-Akt/Akt 升高(P< 0.05)。与氯吡格雷组相比,氯吡格雷 + LY294002 组大鼠神经元病理损伤加重,神经功能缺损评分、脑梗死面积、血清中 S100β、NSE、IL-6 及 TNF-α 水平均升高(P< 0.05),脑组织中 p-PI3K/PI3K、p-Akt/Akt 降低(P< 0.05)。结论 氯吡格雷可通 过激活 PI3K/Akt 通路减轻大鼠脑缺血再灌注损伤,保护脑组织。
关键词:  氯吡格雷  PI3K/Akt 通路  脑缺血再灌注损伤  神经保护
DOI:10.3969/j.issn.1009-6574.2020.01.008
基金项目:
Neuroprotective effect of clopidogrel on cerebral ischemia-reperfusion injury in rats based on PI3K/Akt pathway
Wen Yao, Zheng Wenxu, Jiang Wei, Wang Ling
()
Abstract:
Objective To investigate the neuroprotective effect of clopidogrel on cerebral ischemiareperfusion injury in rats based on PI3K/Akt pathway. Methods Rat models of cerebral ischemia reperfusion were established and randomly divided into model group, clopidogrel group, LY294002 (PI3K/Akt pathway inhibitor) group and clopidogrel + LY294002 group, with 12 rats in each group, and another 12 SD rats were used as sham operation group. After grouping, all rats were scored for neurological deficit and blood was taken from caudal vein to execute the rats. Hematoxylin-eosin (HE) staining was used to detect the pathological changes of neurons in each group, the infarct size of brain tissue was measured by TTC staining, enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum central nervous specific protein (S100β), neuron specific enolase (NSE), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the expression of PI3K/Akt pathway protein in brain tissue was detected by Western blotting. Results Compared with shamoperated group, neuron necrosis and nuclear contraction decreased in model group; neurological deficit score, cerebral infarction area, levels of serum S100β, NSE, IL-6 and TNF-α increased significantly (P < 0.05),while p-PI3K/PI3K and p-Akt/Akt decreased significantly (P < 0.05). Compared with the model group, the pathological damage of neurons in clopidogrel group was alleviated; neurological deficit score, cerebral infarction area, levels of serum S100β, NSE, IL-6 and TNF-α decreased significantly (P < 0.05), while p-PI3K/PI3K and p-Akt/Akt increased significantly (P < 0.05). Neuronal pathological damage in LY294002 group was aggravated; neurological deficit score, cerebral infarction area, levels of serum S100β, NSE, IL-6 and TNF-α increased significantly (P< 0.05), while p-PI3K/PI3K and p-Akt/Akt decreased significantly (P < 0.05). Compared with LY294002 group, the pathological damage of neurons in clopidogrel + LY294002 group was alleviated; the neurological deficit score, cerebral infarction area, levels of serum S100β, NSE, IL-6 and TNF-α decreased significantly (P< 0.05), while p-PI3K/PI3K and p-Akt/Akt increased significantly (P < 0.05). Compared with clopidogrel group, neuropathological damage was aggravated in clopidogrel + LY294002 group; neurological deficit score, cerebral infarction area, levels of serum S100β, NSE, IL-6 and TNF-α increased significantly (P < 0.05), while p-PI3K/PI3K and p-Akt/Akt decreased significantly (P < 0.05). Conclusions Clopidogrel can alleviate cerebral ischemia-reperfusion injury and protect brain tissue by activating PI3K/Akt pathway in rats.
Key words:  Clopidogrel  PI3K/Akt pathway  Cerebral ischemia-reperfusion injury  Neuroprotection

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