人组织激肽释放酶过表达对病毒性心肌炎小鼠心肌纤维化的抑制作用  

Inhibitory effect of human tissue kallikrein overexpression on myocardial fibrosis in mice with viral myocarditis

作　　者：秦又发 蒲荣 邓文龙 朱永坤 杨宇峰 潘春予 QIN You-fa;PU Rong;DENG Wen-long;ZHU Yong-kun;YANG Yu-feng;PAN Chun-yu(Department of Pharmacy,The Third People's Hospital of Dongguan,Guangdong Dongguan 523326,China;Department of Clinical Laboratory,The Third People's Hospital of Dongguan,Guangdong Dongguan 523326,China;Emergency Department,The Third People's Hospital of Dongguan,Guangdong Dongguan 523326,China;Pathology Department,The Third People's Hospital of Dongguan,Guangdong Dongguan 523326,China)

机构地区：[1]东莞市松山湖中心医院药学部,广东东莞523326 [2]东莞市松山湖中心医院检验科,广东东莞523326 [3]东莞市松山湖中心医院急诊科,广东东莞523326 [4]东莞市松山湖中心医院病理科,广东东莞523326

出　　处：《中国医院药学杂志》2020年第10期1126-1131,共6页Chinese Journal of Hospital Pharmacy

基　　金：广东省医学科研基金立项项目(编号:B2017033);广东省中医药局科研项目(编号:20201368)。

摘　　要：目的:探讨过表达人组织激肽释放酶对病毒性心肌炎(VMC)小鼠心肌纤维化的影响。方法:24只4周龄BALb/c雄性小鼠,随机分为正常对照组(Sham组)、模型组(Model组)、病毒性心肌炎+hKLK1基因载体组(EZ.hKLK1组)、病毒性心肌炎+空载体组(EZ.null组)。采用腹腔注射柯萨奇B3病毒液构建VMC模型,通过尾静脉注射高表达人组织激肽释放酶的慢病毒颗粒(pEZ-Lv105-hKLK1)。第30天,心脏超声检测心功能后,断颈处死小鼠,计算心脏体重比,心肌胶原含量以及Ⅰ型和Ⅲ型胶原比值,Western blot法测定hKLK1、TGF-β1蛋白的表达。结果:与Sham组相比,Model组心脏指数、左心室舒张末期内径(LVEDd)、左心室收缩末期内径(LVEDs)、心肌胶原含量、Ⅰ/Ⅲ胶原比值、TGF-β1的表达均显著升高(P<0.05),左心室缩短分数(FS)和射血分数(EF)显著降低(P<0.05),提示造模成功;与Model组相比,EZ.hKLK1组KLK1的表达显著升高(P<0.05),同时心脏指数、LVEDd、LVEDs、心肌胶原含量、Ⅰ/Ⅲ胶原比值、TGF-β1的表达均显著降低(P<0.05),FS和EF显著升高(P<0.05),而EZ.null组差异无显著性(P>0.05)。结论:KLK1可通过调节TGF-β1的表达而发挥抑制VMC小鼠心肌纤维化的作用。OBJECTIVE To study the effect of human tissue kallikrein(KLK)overexpression on myocardial fibrosis in mouse with viral myocarditis(VMC).METHODS 24 four-weeks-old BALB/c male mice were randomly divided into normal control group(sham group),viral myocarditis control group(model group),viral myocarditis+hKLK1 vector group(EZ.hKLK1 group),viral myocarditis+empty vector group(EZ.Null group).The model of VMC mice were constructed by intraperitoneal injection of Coxsackie B3 virus.Human tissue kallikrein1 overexpression lentivirus granules(pEZ-Lv105-hKLK1)were injected via caudal vein.The mice were sacrificed after evaluating cardiac function,and the heart-to-body weight ratio,myocardial collagen content,and the ratio of type I and typeⅢcollagen were calculated,and the expression ofhKLK1 and TGF-β1 protein was determined by Western blot.RESULTS Compared with the sham group,the heart weight ratio,Left Ventricular end-diastolic dimension(LVEDd),Left Ventricular end-systolic dimension(LVEDs),myocardial collagen content,collagenⅠ/Ⅲratio and the expression of TGF-β1 increased,and the Left Ventricular Shortening Fraction(FS),Ejection Fraction(EF)decreased in the model group,which had statistically significance(P<0.05).This indicated the mouse model of VMC was constructed successfully.Compared with the model group,the expression of KLK1 increased,which the heart weight ratio,LVEDd,LVEDs,myocardial collagen content,collagenⅠ/Ⅲratio and the expression of TGF-β1 decreased,and the FS,EF increased in the model group,which had statistically significance(P<0.05).But the differences were not statistically significant in EZ.null group(P>0.05).CONCLUSION KLK1 could inhibit myocardial fibrosis in VMC mouse by regulating the expression of TGF-β1.

关 键 词：人组织激肽释放酶 病毒性心肌炎 心肌纤维化 转化生长因子Β1 

分 类 号：R969[医药卫生—药理学]