RIP1/RIP3通路在大鼠急性脑梗死中的作用  

Study on the role of RIP1/RIP3 pathway in acute cerebral infarction

作　　者：钟春荣 符传艺[3] 杨杰[1] ZHONG Chunrong;FU Chuanyi;YANG Jie(Department of Neurology,Xiangya Hospital,Central South University,Changsha 410008,China)

机构地区：[1]中南大学湘雅医院神经内科,长沙410008 [2]海南省人民医院保健中心四区,海口570311 [3]海南省人民医院神经外科,海口570311

出　　处：《实用医学杂志》2018年第17期2872-2875,共4页The Journal of Practical Medicine

基　　金：海南省自然科学基金项目(编号:817308)

摘　　要：目的探讨程序性坏死信号通路受体相互作用蛋白-1/受体相互作用蛋白-3(RIP1/RIP3)通路在急性脑梗死中的表达和作用。方法将36只雄性Wistar大鼠随机分为3组,每组12只,分别为急性脑梗死组(采用改良Longa线栓法制作急性脑梗死大鼠模型,通过Zea longa 5分制评分法进行神经功能缺损评分并鉴定模型的成功)、对照组(对照组手术步骤同急性脑梗死组,但不插入线栓)和5-(1H-吲哚-3-基甲基)-3-甲基-2-硫酮-4-咪唑烷酮(Nec-1)组(在急性脑梗死模型建立后,按0.6 mg/kg腹腔注射RIP1特异性抑制剂Nec-1溶液,连续注射7 d)。所有大鼠均在7 d后断头取脑组织。采用Western blot分别检测海马RIP1和RIP3表达,ELISA法检测海马肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)表达。结果与对照组比较,急性脑梗死组中海马RIP1/RIP3表达明显增加,炎症因子TNF-α、IL-6分泌增加(P <0.05);Nec-1可显著降低急性脑梗死组海马RIP1和RIP3表达,抑制TNF-α、IL-6分泌,与急性脑梗死组比较,差异具有统计学意义(P <0.05)。结论 RIP1/RIP3通路参与调控急性脑梗死,其抑制剂Nec-1可通过下调RIP1/RIP3通路,抑制炎症,减轻神经元损伤。Objective To investigate the role of receptor interacting protein-1/receptor interacting protein-3(RIP1/RIP3)signaling pathway in a mouse model of acute cerebral infarction.Methods Thirty-six male Wistar rats were randomly divided into acute cerebral infarction group(n=12),sham operation group(n=12)and the Nec-1 group(n=12).The model was established with the modified Longa suture method,and the neurological function was identified by Zea-Longa 5′s method.Rats in the Nec-1 Group were intraperitoneally injected with Nec-1 for a consecutive 7 days after establishing the rat model of acute cerebral infarction.Seven days later,the heads of rats were dissected for brain tissues.Western blot was used to detect the expression of RIP1 and RIP3 in hippocampus,while ELISA method was used to detect the expression of TNF-αand IL-6.Results In contrast to the control group,the expression of RIP1 and RIP3 in hippocampal of the acute cerebral infarction group increased significantly,as well as the levels of TNF-αand IL-6(P<0.05,respectively).Expressions of RIP1 and RIP3 were significantly reduced in hippocampal,and the secretions of TNF-αand IL-6 were inhibited in the Nec-1 group(P<0.05,respectively).Conclusions The RIP1/RIP3 signaling pathway plays an important role in acute cerebral infarction,and Nec-1 can protect neurons against ischemic damage through the RIP1/RIP3 signaling pathway to block inflammation.

关 键 词：急性脑梗死 程序性坏死 RIP1/RIP3 

分 类 号：R743.3[医药卫生—神经病学与精神病学]