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目的探讨糖/血小板反应素-1(TSP-1)/转化生长因子(TGF)β1信号传导途径在糖尿病心肌病发病中的作用。方法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注射建立糖尿病心肌病动物模型,以Masson染色、实时定量逆转录-聚合酶链反应、Western blot技术,检测左室心肌胶原含量、TSP-1、TGFβ1mRNA和蛋白质表达水平的变化。结果与对照组相比,糖尿病心肌病大鼠左室心肌组织胶原含量明显高,存在心肌间质纤维化;TSP-1mRNA和蛋白质表达均明显高,TGFβ1mRNA、活性和非活性TGFβ1蛋白质表达亦明显高;TSP-1、TGFβ1mRNA水平与空腹血糖、心肌组织胶原含量以及左室舒张功能指标均明显相关,TSP-1、活性TGFβ1蛋白质表达水平与空腹血糖、心肌组织胶原含量以及左室舒张功能指标之间亦存在明显的相关关系,但非活性TGFβ1蛋白质表达水平与空腹血糖、心肌组织胶原含量以及左室舒张功能指标之间无相关性。结论糖/TSP-1/TGFβ1信号传导途径在糖尿病心肌病时心肌间质纤维化发生发展过程中可能起着重要的作用,为临床上糖尿病心肌病的治疗提供了新的靶点。
Objective To investigate the role of TSP-1 / TGFβ1 signaling pathway in the pathogenesis of diabetic cardiomyopathy. Methods High-fat and high-calorie diet was used to induce insulin resistance. Small-dose streptozotocin (STZ) injection was used to establish animal models of diabetic cardiomyopathy. Masson staining, real-time quantitative reverse transcription polymerase chain reaction and Western blot were used to detect left ventricular Collagen content, TSP-1, TGFβ1 mRNA and protein expression level changes. Results Compared with the control group, the content of collagen in left ventricular myocardium in diabetic cardiomyopathy rats was significantly higher, there was myocardial fibrosis; the expression of TSP-1 mRNA and protein were significantly higher, and the expressions of TGFβ1 mRNA, active and non-active TGFβ1 protein were also significantly higher ; TSP-1, TGFβ1mRNA levels and fasting blood glucose, myocardial collagen content and left ventricular diastolic function indicators were significantly related to TSP-1, active TGFβ1 protein expression levels and fasting blood glucose, myocardial tissue collagen content and left ventricular diastolic function between indicators There was also a significant correlation, but there was no correlation between non-active TGFβ1 protein expression and fasting blood glucose, myocardial collagen content and left ventricular diastolic function. Conclusion The signal pathway of glucose / TSP-1 / TGFβ1 may play an important role in the development of myocardial interstitial fibrosis in diabetic cardiomyopathy, which may provide a new target for the treatment of diabetic cardiomyopathy.