目的:观察吡格列酮对大鼠缺血/再灌注损伤心肌转化生长因子β1(TGFβ1)表达的影响。方法:30只SD大鼠随机分为5组(n=6):缺血/再灌注组、吡格列酮5 mg/(kg.d)组、吡格列酮10 mg/(kg.d)组、吡格列酮20 mg/(kg.d)组、吡格列酮20 mg/(kg.d)+过氧化物酶体增殖物激活受体γ(PPARγ)特异性阻断剂GW9662组,利用在体结扎左前降支的方法建立缺血/再灌注损伤模型,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL法)检测心肌细胞凋亡,RT-PCR方法检测心肌组织TGFβ1 mRNA的变化,Western blot方法检测心肌组织TGFβ1蛋白的变化。结果:TUNEL法显示吡格列酮抑制缺血/再灌注心肌细胞凋亡,吡格列酮上调TGFβ1表达,GW9662逆转吡格列酮对凋亡细胞的抑制作用,抑制吡格列酮促进TGFβ1表达上调的作用。结论:吡格列酮可抑制缺血/再灌注损伤诱导的心肌细胞凋亡,吡格列酮可促进TGFβ1上调,这两种作用是由PPARγ介导的。
Objective: To investigate the effects of pioglitazone on transforming growth factor β1(TGFβ1) expression in ischemia/reperfusion injury myocardium of rats.Methods: Thirty SD rats were randomly divided into five groups(n=6): ischemia/reperfusion group,pioglitazone 5 mg/(kg·d) group,pioglitazone 10 mg/(kg·d) group,pioglitazone 20 mg/(kg·d) group and pioglitazone 20 mg/(kg·d) + peroxisome proliferator-activated receptor γ(PPARγ) specific antagonist GW9662 group.Left anterior descending coronary artery of rats were ligated for 30 min and reperfused for 120 min to establish the model of ischemia/reperfusion in vivo.RT-PCR was performed to detect the expression of TGFβ1 mRNA.Western blot was performed to detect the expression of TGFβ1 protein.Results: Myocardial apoptosis was significantly suppressed by pioglitazone.Pioglitazone upregulated TGFβ1 expression both in mRNA and protein level.GW9662 reversed the inhibition of myocardial apoptosis and the upregulation of TGFβ1 expression by pioglitazone.Conclusion: Pioglitazone can inhibit the myocardial apoptosis induced by ischemia/reperfusion.Pioglitazone may protect the myocardium from ischemia/reperfusion via upregulation of TGFβ1.This protection may be mediated by PPARγ.