SMOC1对高血压大鼠血小板功能和内皮功能参数的影响  

Effects of SMOC1 on platelet function and endothelial function parameters in hypertensive rats

作　　者：郝瑞 王鑫 朱文敏 HAO Rui;WANG Xin;ZHU Wenmin(Department of Cardiovascular Medicine,Central Hospital Affiliated to Shandong First Medical University,Jinan 250033,China;Shandong Labor Vocational and Technical College)

机构地区：[1]山东第一医科大学附属中心医院心血管内科,济南250033 [2]山东劳动职业技术学院

出　　处：《山西医科大学学报》2024年第11期1404-1412,共9页Journal of Shanxi Medical University

基　　金：山东省自然科学基金面上项目(ZR2021MH019);山东第一医科大学附属中心医院“常青树”青年医生托举计划项目(TJJH2021007)。

摘　　要：目的 探讨分泌型模块化钙结合蛋白1(SMOC1)对高血压(HBP)大鼠血小板功能和内皮功能的影响。方法 选择12只WKY大鼠作为对照组,将SHR大鼠随机分为5组:SHR组、阴性对照shRNA(sh-NC)组、SMOC1 shRNA(sh-SMOC1)组、阴性对照过表达(oe-NC)组和SMOC1过表达(oe-SMOC1)组,每组12只。各组大鼠尾静脉注射生理盐水或对应的慢病毒,每隔7 d注射1次,共注射4次。末次注射慢病毒8 d后,测量大鼠尾动脉收缩压(SBP)、舒张压(DBP)、血小板功能参数[血小板计数(PLT)、平均血小板体积(MPV)、血小板分布宽度(PDW)、血小板压积(PCT)]、血清内皮功能参数[血管紧张素Ⅱ(AngⅡ)、内皮素-1(ET-1)、一氧化氮(NO)]。使用苏木素伊红(HE)染色和Masson三色染色观察大鼠腹主动脉形态。按照试剂盒说明书检测腹主动脉组织中超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)、单核细胞趋化蛋白1(MCP-1)、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平。RT-qPCR检测腹主动脉组织中SMOC1 mRNA水平。Western blot检测腹主动脉组织中SMOC1、磷酸化磷脂酰肌醇3激酶(p-PI3K)、磷酸化蛋白激酶B(p-AKT)的表达。结果 与SHR组和sh-NC组比较,shSMOC1组大鼠腹主动脉组织中SMOC1的mRNA和蛋白水平降低(P<0.05),SBP、DBP、PLT、MPV、PDW、PCT、AngⅡ和ET-1水平均降低(P<0.05),而NO水平升高(P<0.05);腹主动脉形态明显改善,胶原面积减少(P<0.05),腹主动脉p-PI3K、p-AKT、MDA、MCP-1、TNF-α和IL-6水平均降低(P<0.05),SOD和CAT水平均升高(P<0.05)。与SHR组和oe-NC组比较,oe-SMOC1组大鼠腹主动脉组织中SMOC1的mRNA和蛋白水平升高(P<0.05),SBP和DBP、PLT、MPV、PDW、PCT、AngⅡ和ET-1水平均升高(P<0.05),而NO水平降低(P<0.05);腹主动脉形态恶化,胶原面积增加(P<0.05),腹主动脉p-PI3K、p-AKT、MDA、MCP-1、TNF-α和IL-6水平均升高(P<0.05),SOD和CAT水平均降低(P<0.05)。结论 SMOC1的异常高表达可能通过损害血小板功能和内Objective To investigate the effect of secretory modular calcium binding protein 1(SMOC1)expression on platelet func-tion and endothelial function in hypertensive(HBP)rats.Methods Twelve WKY rats were selected as control group,and SHR rats were randomly divided into 5 groups(n=12 in each group):SHR group,shRNA negative control(sh-NC)group,SMOC1 shRNA(sh-SMOC1)group,overexpression negative control(oe-NC)group and SMOC1 overexpression(oe-SMOC1)group.Rats in each group were given tail vein injection of normal saline or lentivirus once every seven days for four times.At day 8 after the last lentivirus injec-tion,systolic blood pressure(SBP)and diastolic blood pressure(DBP)of rat tail artery,platelet function parameters[platelet count(PLT),mean platelet volume(MPV),platelet distribution width(PDW),platelet volume(PCT)],serum endothelial function para-meters[angiotensinⅡ(AngⅡ),endothelin-1(ET-1),nitric oxide(NO)]were measured.The morphology of abdominal aorta was ob-served by hematoxylin-eosin(HE)staining and Masson trichrome staining.The levels of superoxide dismutase(SOD),catalase(CAT),malondialdehyde(MDA),monocyte chemoattractant protein-1(MCP-1),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in abdominal aorta tissue were measured according to the kit instructions.SMOC1 mRNA level in abdominal aorta tissue was detected by RT-qPCR.The expressions of SMOC1,phosphatidylinositol 3 kinase(p-PI3K)and phosphorylated protein kinase B(p-AKT)in abdominal aorta tissue were detected by Western blot.Results Compared with SHR group and sh-NC group,the mRNA and protein levels of SMOC1 in abdominal aortic tissue of rats were decreased in sh-SMOC1 group(P<0.05),the levels of SBP,DBP,PLT,MPV,PDW,PCT,AngⅡand ET-1 were decreased(P<0.05),NO level was increased(P<0.05),the morphology of abdominal aorta was significantly improved,the collagen area of abdominal aorta decreased(P<0.05),the levels of p-PI3K,p-AKT,MDA,MCP-1,TNF-αand IL-6 in abdominal aorta were increased(P<0.05),and the levels of SOD and CAT were increased(P<0

关 键 词：高血压 分泌型模块化钙结合蛋白1 血小板 内皮 腹主动脉重塑 氧化应激 炎症 

分 类 号：R544.1[医药卫生—心血管疾病]