S1P/S1P1信号通路在糖尿病心肌病大鼠心肌损伤中的作用与机制  

Role and mechanism of S1P/S1P1 signaling pathway in cardiac injuries of diabetic cardiomyopathy rats

作　　者：莫海亮[1] 姜佳美[1] 刘畅[1] 吴子君[1] 黄瑞娜[1] 梁国标[1] 陈科辉 李腾[1] 李上海[1] 闫海[1] 何松坚[1] 游琼[1] 吴铿[1] 郭润民[1] MO Hailiang;JIANG Jiamei;LIU Chang;WU Zijun;HUANG Ruina;LIANG Guobiao;CHEN Kehui;LI Teng;LI Shanghai;YAN Hai;HE Songjian;YOU Qiong;WU Keng;GUO Runmin(Department of Cardiology,the Affiliated Hospital of Guangdong Medical University,Zhanjiang 524001,China)

机构地区：[1]广东医学院附属医院心血管内科,广东湛江524001

出　　处：《中国医药科学》2017年第15期9-12,共4页China Medicine And Pharmacy

基　　金：国家自然科学基金(81670348);广东省医学科学技术研究基金(A2016143);广东省自然科学基金(2016A030313678;2015A030310359);广东省湛江市财政资金科技专项竞争性分配项目(2014A01033)

摘　　要：目的探讨S1P/S1P1信号通路在糖尿病心肌病大鼠心肌损伤中的作用与机制。方法 40只SD大鼠分为正常对照组和2型糖尿病心肌病,每组各20只,链脲佐菌素(streptozotocin,STZ)诱导老鼠建立2型DCM模型,STZ处理8周后,给予老鼠S1P1受体激动剂、S1P1受体拮抗剂干预,观察S1P1受体激动剂、S1P1受体拮抗剂对DCM心肌损伤的影响;HE染色检测心肌组织病理改变,免疫印迹法检测心肌组织Sphk1和S1P1的表达,ELISA法检测组织匀浆液S1P的表达,组织Sph K1激酶活性定量检测试剂盒测定Sph K1酶活性。结果与正常对照组比较,DCM组大鼠心脏凋亡增多、心肌肥大,同时Sph K1及其产物S1P表达增加,S1P1受体下调,S1P1受体拮抗剂干预加重DCM心肌损伤,而S1P1受体激动剂能减轻心肌凋亡、心肌肥大、胶原沉积等。结论 S1P/S1P1信号通路被抑制可能是DCM心肌损伤的机制之一,调控该通路可能是DCM心肌损伤的防治靶点。Objective To investigate the role and mechanism of S1P/S1P1signaling pathway in cardiac injuriesof diabetic cardiomyopathy(DCM)rats.Methods40SD rats were randomly divided into normal control group anddiabetic cardiomyopathy(DCM)group with20cases in each.They were treated with normal saline and streptozotocin(STZ)respectively.After injection STZ for8weeks,diabetic rats were administrated with S1P1receptor agonists orS1P1receptor antagonists,and then these effects on cardiac injuries of DCM rats were explored.The pathologicalchanges of myocardial tissue were detected by HE staining.Expressions of sphk1and S1P1in heart tissues were testedusing Western blotting assay.S1P level in rat hearts tissue homogenate was tested using ELISA kit.SphK1enzymicactivity was measured by tissue SphK1activity quantity kit.Results Compared with control group,cardiomyocyteapoptosis,left ventricular hypertrophy in diabetic rats were markedly elevated.Meanwhile,sphk1expression andactivity,and S1P1expression in hearts tissue were upregulated,while S1P1receptor was dramatically downregulated.However,S1P1receptor antagonists could exacerbate cardiac injuries,and S1P1receptor agonists could improvecardiac injuries.Conclusion S1P/S1P1signaling pathway may contribute to the cardiac injuries of DCM rats,whichwill be regarded as therapeutic target.

关 键 词：鞘氨醇激酶-1 1-磷酸鞘氨醇 1-磷酸鞘氨醇受体1 糖尿病心肌病 凋亡 

分 类 号：R587.2[医药卫生—内分泌]