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目的探讨缬沙坦逆转糖尿病心肌病(DCM)心肌间质纤维化的作用机制。方法雄性Wistar大鼠40只随机分为3组对照组(8只),DCM组(16只),缬沙坦干预组(16只)。采用高脂高热量饮食诱导出胰岛素抵抗,加小剂量链脲佐菌素(STZ)注射建立DCM动物模型。利用Masson染色、实时定量逆转录-聚合酶链反应、Western印迹技术,检测左室心肌胶原含量、血小板反应素-1(TSP-1)、TGFβ1mRNA表达水平和蛋白质表达的变化。结果与对照组相比,DCM大鼠左室心肌组织胶原含量明显升高(11%±3%vs17%±3%,P<0·01),存在心肌间质纤维化;TSP-1mRNA和蛋白质表达水平均明显升高(0·0089±0·0034vs0·0141±0·0037,96±17vs130±17,均P<0·05),TGFβ1mRNA、活性和非活性TGFβ1蛋白质表达水平亦明显升高(0·0054±0·0009vs0·0126±0·0057,103±18vs143±17,99±20vs155±35,均P<0·01);应用缬沙坦进行干预治疗后,除非活性TGFβ1蛋白质表达水平无明显变化外,上述异常均明显减轻。结论缬沙坦通过抑制TSP-1/TGFβ1信号传导途径在逆转DCM心肌间质纤维化发生发展过程中起着重要的作用。
Objective To investigate the mechanism of valsartan in reversing myocardial interstitial fibrosis in diabetic cardiomyopathy (DCM). Methods Forty male Wistar rats were randomly divided into three groups: control group (n = 8), DCM group (n = 16) and valsartan intervention group (n = 16). Insulin resistance was induced by high-fat and high-calorie diet, and DCM animal model was established by injecting low-dose streptozotocin (STZ). Masson staining, real-time quantitative reverse transcription-polymerase chain reaction and Western blotting were used to detect the changes of collagen content, thrombospondin-1 (TSP-1), TGFβ1 mRNA and protein expression in left ventricular myocardium. Results Compared with the control group, the content of collagen in left ventricular myocardium of DCM rats increased significantly (11% ± 3% vs 17% ± 3%, P <0.01), and there was myocardial interstitial fibrosis. TSP-1 mRNA and protein (0 · 0089 ± 0 · 0034vs0 · 0141 ± 0 · 0037, 96 ± 17vs130 ± 17, all P <0 · 05), TGFβ1mRNA, active and inactive TGFβ1 protein expression levels were also significantly increased 0 · 0054 ± 0 · 0009vs0 · 0126 ± 0 · 0057,103 ± 18vs143 ± 17,99 ± 20vs155 ± 35, all P <0 · 01). After intervention with valsartan, unless the expression level of active TGFβ1 protein was not Significant changes, the above abnormalities were significantly reduced. Conclusion Valsartan plays an important role in reversing the development of myocardial interstitial fibrosis by inhibiting TSP-1 / TGFβ1 signaling pathway.