雷公藤内酯醇通过JAK2/STAT3通路抑制脑缺血再灌注大鼠炎症反应和神经元凋亡  

Triptolide inhibits inflammatory response and neuronal apoptosis in cerebral ischemia-reperfusion rats via JAK2/STAT3 pathway

作　　者：吴洁[1] 董魁[2] 霍好利[1] 邢瑞敏[1] 陈晨[1] WU Jie;DONG Kui;HUO Hao-li;XING Rui-min;CHEN Chen(Department of Pharmacy,Handan Central Hospital,Handan 056008;Department of Gastroenterology,Handan First Hospital,Handan 056001,China)

机构地区：[1]邯郸市中心医院药学部,河北邯郸056008 [2]邯郸市第一医院消化内科,河北邯郸056001

出　　处：《解剖科学进展》2024年第1期43-46,50,共5页Progress of Anatomical Sciences

基　　金：河北省医学科学研究课题(20220570)。

摘　　要：目的 研究雷公藤内酯醇(TPL)对脑缺血再灌注(CIR)大鼠炎症反应和神经元凋亡的影响,并探讨其可能的分子机制。方法 取192只SD大鼠设假手术组、模型组、丁苯酞组和TPL低、中、高剂量组,各32只,采用线栓阻断大脑中动脉2 h的方法复制CIR大鼠模型。再灌注24 h后,检测大鼠神经功能、脑梗死体积、脑含水量;观察缺血半暗带皮层神经元病理学变化和神经元凋亡;ELISA法检测缺血侧皮层组织炎症因子水平,Western blot法检测缺血侧皮层组织Janus激酶2/信号转导与转录激活子3(JAK2/STAT3)通路蛋白、高迁移率族蛋白B1(HMGB1)及凋亡相关蛋白表达。结果 TPL中、高剂量和丁苯酞明显降低CIR大鼠神经功能缺失评分、脑梗死体积和脑含水量(P<0.05);明显改善缺血半暗带皮层神经元病理学变化,降低神经元凋亡率(P<0.05);降低缺血侧皮层组织TNF-α、IL-1β水平(P<0.05),降低p-JAK2/JAK2、p-STAT3/STAT3、Bax/Bcl-2表达比值和HMGB1、Cleaved Caspase-3表达量(P<0.05)。除神经功能缺失评分、脑含水量外,TPL高剂量对其他指标的作用均优于丁苯酞(P<0.05)。结论 TPL可能通过抑制JAK2/STAT3通路活化对CIR大鼠炎症反应和神经元凋亡起抑制作用,降低大鼠CIR损伤。Objective To investigate the effects of triptolide(TPL)on inflammation and neuronal apoptosis in rats with cerebral ischemia-reperfusion(CIR),and to explore its possible molecular mechanism.Methods A total of 192 SD rats were divided into sham operation group,model group,butylphthalide group,and low,medium and high dose TPL groups,with 32 rats in each group.The rat model of CIR was established by occlusion of the middle cerebral artery for 2 h.After reperfusion for 24 h,the neurological function,cerebral infarct volume and brain water content were measured;the pathological changes and neuronal apoptosis in the cortical neurons of the ischemic penumbra were observed;the levels of inflammatory factors in the ischemic cortex were measured by ELISA;the expressions of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway proteins,high mobility group protein B1(HMGB1)and apoptosis-related proteins in the ischemic cortex were detected by Western blot.Results The middle and high dose TPL and butylphthalide significantly reduced the neurological deficit score,cerebral infarct volume and brain water content in CIR rats(P<0.05);significantly improved the pathological changes of the cortical neurons in the ischemic penumbra and reduced the apoptosis rate(P<0.05);reduced the levels of TNF-αand IL-1βin the ischemic cortex(P<0.05),reduced the expression ratios of p-JAK2/JAK2,p-STAT3/STAT3,and Bax/Bcl-2,and the expression levels of HMGB1 and cleaved Caspase-3(P<0.05).Except for the neurological deficit score and brain water content,the effects of high dose TPL on other indicators were better than butylphthalide(P<0.05).Conclusion TPL may inhibit the inflammatory response and neuronal apoptosis in CIR rats by inhibiting the activation of JAK2/STAT3 pathway,and reduce the injury of CIR rats.

关 键 词：雷公藤内酯醇 脑缺血再灌注 JAK2/STAT3通路 炎症 神经元凋亡 

分 类 号：R743.31[医药卫生—神经病学与精神病学]