激活受体PPAR-γ调节压力超负荷诱导的大鼠心肌纤维化的研究  

Study of PPAR-γregulating myocardial fibrosis induced by pressure overload in rats

作　　者：王丹 卢迎宏 井海云 王梦超 李智慧 包晓青 陈文哲 刘凯 邢瑞星 WANG Dan;LU Yinghong;JING Haiyun;WANG Mengchao;LI Zhihui;BAO Xiaoqing;CHEN Wenzhe;LIU Kai;XING Ruixing(Department of Cardiology,Zhengzhou Central Hospital Affiliated to Zhengzhou University,Zhengzhou 450007,China)

机构地区：[1]郑州大学附属郑州中心医院心血管内科,郑州450007

出　　处：《中国免疫学杂志》2022年第21期2572-2577,共6页Chinese Journal of Immunology

基　　金：2017年河南省科技攻关计划项目(2017T02093)。

摘　　要：目的:探讨重组慢病毒介导的稳定过表达过氧化物酶体增殖因子活化受体-γ(PPAR-γ)基因对压力超负荷诱导的大鼠心肌功能的作用及可能机制。方法:将40只SD大鼠随机分为假手术组、模型组、Lv-NC组和Lv-PPAR-γ组,每组10只,假手术组大鼠开腹后直接关闭腹腔,其余3组采用腹主动脉缩窄术构建左心室肥厚大鼠模型,术后3 d Lv-NC组、Lv-PPAR-γ组分别尾静脉注射20μl 1×10^(9)TU/ml Lv-NC、Lv-PPAR-γ,假手术组、模型组注射等量生理盐水。4周后,RT-PCR、Western blot法验证各组大鼠心肌组织中PPAR-γ、α平滑肌肌动蛋白(α-SMA)、TGF-β、纤维连接蛋白(FN)、诱导型一氧化氮合酶(iNOS)、IL-10表达水平,ELISA法检测心肌肌钙蛋白Ⅰ(cTnⅠ)、肌酸激酶同工酶(CK-MB)和肌红蛋白(Mb)水平;HE和Masson染色观察心肌纤维化程度及心肌胶原含量。结果:模型组和Lv-NC组大鼠心肌中PPAR-γ表达水平较假手术组降低(P<0.05),Lv-PPAR-γ组大鼠心肌中PPAR-γ表达水平较模型组显著升高(P<0.05);模型组和Lv-NC组大鼠心率(HR)、左心室收缩压(LVSP)、左室短轴缩短率(FP)较假手术组降低(P<0.05),cTnⅠ、CK-MB、Mb、胶原容积分数(CVF)、α-SMA、TGF-β、FN、iNOS、IL-10较假手术组升高(P<0.05);Lv-PPAR-γ组大鼠HR、LVSP、FP较模型组升高(P<0.05),cTnⅠ、CK-MB、Mb、CVF、α-SMA、TGF-β、FN、iNOS、IL-10较模型组降低(P<0.05)。结论:稳定表达PPAR-γ可减轻压力超负荷大鼠左心室损伤及纤维化程度,其机制与促进抗炎症因子、抑制促炎症介质表达,减少炎症反应有关。Objective:To explore the effects and possible mechanism of recombinant lentivirus mediated stable overexpression of peroxisome proliferator-activated receptor-γ(PPAR-γ)gene on myocardial function in rats induced by pressure overload.Methods:Forty SD rats were randomly divided into sham operation group,model group,Lv-NC group and Lv-PPAR-γgroup,with 10 rats in each group.In sham operation group,abdominal cavities of rats were directly closed after laparotomy,while rat models of left ventricular hypertrophy were constructed by abdominal aortic coarctation in the other three groups.3 d after surgery,Lv-NC group and Lv-PPAR-γgroup were injected with 20μl 1×10^(9)TU/ml Lv-NC and Lv-PPAR-γthrough caudal vein,while sham operation group and model group were injected with the same volume of normal saline.4 weeks later,expression levels of PPAR-γ,α-smooth muscle actin(α-SMA),TGF-β,fibronectin(FN),inducible nitric oxide synthase(iNOS)and IL-10 in myocardial tissues of each group were verified by RT-PCR and Western blot.The levels of cardiac troponinⅠ(cTnⅠ),creatine kinase MB(CK-MB)and myoglobin(Mb)were detected by ELISA.HE and Masson staining were used to observe the severity of myocardial fibrosis and contents of myocardial collagens.Results:The expression level of PPAR-γin model group and Lv-NC group were lower than that in sham operation group(P<0.05),which was significantly higher in Lv-PPAR-γgroup than model group(P<0.05).The heart rate(HR),left ventricular systolic pressure(LVSP)and left ventricular fractional shortening(FP)in model group and Lv-NC group were lower than those in sham operation group(P<0.05),while cTnⅠ,CK-MB,Mb,collagen volume fraction(CVF),α-SMA,TGF-β,FN,iNOS and IL-10 were higher than those in sham operation group(P<0.05).HR,LVSP and FP in Lv-PPAR-γgroup were higher than those in model group(P<0.05),while cTnⅠ,CK-MB,Mb,CVF,α-SMA,TGF-β,FN,iNOS and IL-10 were lower than those in model group(P<0.05).Conclusion:Stable expression of PPAR-γcan relieve left ventricular injury and

关 键 词：高血压 心肌肥厚 心肌纤维化 过氧化物酶体增殖因子活化受体Γ 炎症介质 

分 类 号：R542.23[医药卫生—心血管疾病]