通过JAK2/STAT3信号通路观察电针减轻MIRI炎性反应机制研究  

JAK2/STAT3 Signaling Pathway Mechanism of Electroacupuncture in Reducing Inflammatory Response to Myocardial Ischemia-Reperfusion Injury

作　　者：丁雅萍 华斌 刘琼琼 吴双 徐森磊 夏雪峰 姜春宏 贺丽丽 顾一煌[1] Ding Yaping;Hua Bin;Liu Qiongqiong;Wu Shuang;Xu Senlei;Xia Xuefeng;Jiang Chunhong;He Lili;Gu Yihuang(College of Acupuncture and Massage·Health and Rehabilitation College,Nanjing University of Chinese Medicine,Nanjin 210000,China;Wuxi Xishan District Hospital of Chinese Medicine,Wuxi 214000,China)

机构地区：[1]南京中医药大学针灸推拿学院·养生康复学院,南京210000 [2]无锡市锡山区中医医院,无锡214000

出　　处：《世界科学技术-中医药现代化》2023年第10期3436-3444,共9页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委员会面上项目(81974583):基于自噬-炎症调控的电针预处理减轻心肌IR损伤的mTOR/NLRP3信号机制研究,负责人:顾一煌;江苏省中药局江苏省中医药领军人才项目(SLJ0226):负责人:顾一煌;江苏省研究生科研创新计划项目(KYCX22_1952):电针减轻MIRI炎性反应的JAK2/STAT3信号通路机制研究,负责人:丁雅萍

摘　　要：目的通过观察电针“内关”穴观察心肌缺血再灌注损伤(MIRI)大鼠心肌组织中的酪氨酸激酶-2(JAK2)和信号转导及转录激活因子-3(STAT3)表达,探讨电针上调JAK2/STAT3信号通路,促进抗炎因子表达,减少MIRI损伤的作用机制。方法将超声心动图正常的30只雄性SD大鼠随机分为假手术组、模型组和电针组,每组10只。模型组和电针组采用冠状动脉左前降支(LAD)结扎法制备MIRI模型,假手术组仅穿线不结扎。电针组在造模术后第1、3、5天进行双侧“内关”穴电针(疏密波,2 Hz/100 Hz,2 mA)干预,每天1次,每次20 min。采用超声心动图观察术后第1、3、5天大鼠左心室射血分数(LVEF)以评估心功能;HE染色观察大鼠心肌病理形态变化;马松染色观察大鼠心肌纤维化情况;ELISA检测心肌组织中IL-4、IL-6的表达;免疫组化检测心肌组织中IL-1β、IL-10的表达情况;Western blot法测定梗死区心肌组织JAK2、p-JAK2、STAT3、p-STAT3蛋白表达。结果与假手术组比较,模型组大鼠术后EF明显降低(P<0.05),纤维化面积增大(P<0.05),IL-4、IL-6、IL-10、IL-1β含量均升高(P<0.05),JAK2、p-JAK2、STAT3、p-STAT3蛋白表达含量均升高(P<0.05);与模型组比较,电针组大鼠EF上升(P<0.05),电针组大鼠纤维化面积减小(P<0.05),IL-4、IL-10含量升高,IL-6、IL-1β含量下降(P<0.05),JAK2、p-JAK2、STAT3、p-STAT3蛋白表达含量均升高(P<0.05)。结论电针内关穴可显著上调JAK2/STAT3信号通路,减少促炎因子的分泌,增加抗炎因子的表达,减轻大鼠心肌缺血再灌注损伤。Objective To observe the expression of tyrosine kinase 2(JAK2)and signal transducer and activator of transcription 3(STAT3)in myocardial tissue of rats with myocardial ischemia-reperfusion injury(MIRI)by electroacupuncture at"Neiguan"point,and explore the mechanism of electroacupuncture in up regulating JAK2/STAT3 signal pathway,promoting the expression of anti-inflammatory factors,and reducing MIRI injury.Methods Thirty male SD rats with normal echocardiography were randomly divided into sham operation group,model group and electroacupuncture group,with 10 rats in each group.MIRI models were prepared by ligation of left anterior descending coronary artery(LAD)in model group and electroacupuncture group,while in sham operation group,only threading was performed without ligation.In the electroacupuncture group,electroacupuncture(density wave,2 Hz/100 Hz,2 mA)at bilateral"Neiguan"points was performed on the 1st,3rd and 5th days after the modeling operation,once a day,20 minutes each time.The left ventricular ejection fraction(LVEF)of rats on the 1st,3rd and 5th day after operation was observed by echocardiography to evaluate cardiac function;HE staining was used to observe the pathological changes of rat myocardium;The myocardial fibrosis was observed by Masson staining;The expression of IL-4 and IL-6 in myocardium was detected by ELISA;The expressions of IL-1βand IL-10 in myocardial tissue were detected by immunohistochemistry;The expression of JAK2,p-JAK2,STAT3,p-STAT3 protein in myocardial infarction area was measured by Western blot.Results Compared with sham operation group,EF in model group decreased significantly(P<0.05),fibrosis area increased(P<0.05),IL-4,IL-6,IL-10,IL-1βThe content of JAK2,p-JAK2,STAT3,p-STAT3 protein increased(P<0.05);Compared with the model group,the EF of rats in the electroacupuncture group increased(P<0.05),the fibrotic area of rats in the electroacupuncture group decreased(P<0.05),the content of IL-4 and IL-10 increased,and IL-6 and IL-1βThe expression of JAK2,p-JAK2,STAT3,p-STAT

关 键 词：电针 心肌缺血再灌注损伤 炎性反应 JAK2/STAT3信号通路 

分 类 号：R245.97[医药卫生—针灸推拿学]