异丹叶大黄素调控PI3K/Akt信号通路对大鼠脑缺血再灌注损伤的神经保护作用  

The neuroprotective effect of isorhapontigenin on cerebral ischemia/reperfusion injury in rats by regulating PI3K/Akt signaling pathway

作　　者：孙家贺 SUN Jiahe

机构地区：[1]济宁市第一人民医院泗水院区,山东济宁273200

出　　处：《中医临床研究》2024年第16期81-86,共6页Clinical Journal Of Chinese Medicine

基　　金：青岛大学医疗集团科研专项基金资助项目(YLJT20202035)。

摘　　要：目的:验证异丹叶大黄素(Isorhapontigenin,ISO)通过调节磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(Akt)信号通路减轻缺血再灌注大鼠脑缺血半暗带神经元损伤的作用及机制。方法:随机选择60只SD级别雄性大鼠,分为假手术组、模型组、ISO组,每组20只。假手术组给予手术但未穿线,模型组采用线栓法建立脑缺血再灌注损伤模型,ISO组再灌注后2 h腹腔内注射ISO。参考Z-Longa 5级评分标准评估神经功能缺损情况,采用氯化三苯基四氮唑染色法测定脑梗死率,采用苏木素-伊红染色法、尼氏染色法观察脑组织及神经元损伤情况,采用酶联免疫吸附测定脑组织中白细胞介素(Interleukin,IL)-6、IL-1β、肿瘤坏死因子-α(Tumor Necrosis Factor-α,TNF-α)、超氧化物歧化酶(Superoxide Dismutase,SOD)及丙二醛(Malondialdehyde,MDA)含量,采用蛋白质印迹法检测磷酸化Akt(p-Akt)、磷酸化PI3K(p-PI3K)蛋白表达水平。结果:本研究中ISO组大鼠神经功能损伤程度、脑梗死率、炎症因子水平均显著低于模型组(P<0.05),SOD水平显著高于模型组(P<0.05),脑组织较模型组有较低的炎性细胞浸润及较完整的神经元结构。模型组p-Akt、PI3K蛋白表达显著下降,ISO组p-Akt、PI3K蛋白表达较模型组显著升高(P<0.05)。结论:ISO可能通过激活PI3K/Akt信号通路清除氧自由基、减轻炎症反应,进而减轻脑缺血再灌注对脑细胞造成的损伤。Objective:To investigate the effect and action mechanism of isorhapontigenin(ISO)on ischemic penumbra neurons injury in ischemia-reperfusion rats by regulating PI3K/Akt signaling pathway.Methods:A total of 60 male SD rats were randomly divided into the sham operation group,the model group and the ISO group,with 20 rats in each group.The sham operation group was given operation but no thread.The model group was given thread embolism method to establish cerebral ischemia-reperfusion injury model.The ISO group was injected ISO 2 hours after reperfusion.Neurological impairment was assessed by Z-Longa.Cerebral infarction rate was measured by TTC staining.Brain tissue and neuron injury were observed by HE staining and Nissl staining.IL-6,IL-1β,tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD)and malondialdehyde(MDA)content were detected by ELISA.The levels of p-Akt and p-PI3K were detected by Western blotting.Results:The nerve function injury degree,cerebral infarction rate and inflammatory factor level of rats in the ISO group were significantly lower than those in the model group(P<0.05),the level of SOD in the ISO group was significantly higher than that in the model group(P<0.05).The brain tissue in the ISO group had lower inflammatory cell infiltration and more complete neuron structure compared with the model group.The protein expressions of p-Akt and PI3K in the model group were decreased significantly,and the protein expressions of p-Akt and PI3K in the ISO group were increased significantly compared with the model group(P<0.05).Conclusion:ISO may clear oxygen free radicals and reduce inflammation by activating PI3K/Akt signaling pathway to reduce brain cell injury caused by cerebral ischemia-reperfusion.

关 键 词：异丹叶大黄素 磷脂酰肌醇3激酶/蛋白激酶B 缺血再灌注损伤 氧化应激 炎症反应 

分 类 号：R651.1[医药卫生—外科学]