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目的探讨氯沙坦钾和辛伐他汀合用对1型糖尿病大鼠心肌组织中结缔组织生长因子(CTGF)和转化生长因子-β1(TGF-β1)表达的影响及其对糖尿病心肌病的保护作用。方法雄性SD大鼠90只,随机分为氯沙坦钾干预组、辛伐他汀干预组、氯沙坦钾联合辛伐他汀干预组、糖尿病组、正常对照组共5组,于实验的4周、8周和12周每组分别取6只大鼠,测定血糖、胰岛素、心重指数及心肌细胞面积,免疫组化测定心肌CTGF和TGF-β1的蛋白变化,于实验的12周用荧光定量RT-PCR测定心肌中CTGF和TGF-β1的mRNA水平。结果糖尿病组心重指数、心肌细胞面积增加,心肌组织CTGF和TGF-β1的蛋白及mRNA表达均明显升高(P<0.05),各干预组上述指标均明显减轻(P<0.05),其中联合组更明显(P<0.05)。结论氯沙坦钾和辛伐他汀均能抑制糖尿病大鼠心肌CTGF及TGF-β1的表达,起到心脏保护作用,两药联用具有协同作用。
Objective To investigate the effects of losartan potassium and simvastatin on the expression of connective tissue growth factor (CTGF) and transforming growth factor-β1 (TGF-β1) and its protective effect on diabetic cardiomyopathy in type 1 diabetic rats . Methods 90 male Sprague-Dawley rats were randomly divided into 5 groups: losartan potassium intervention group, simvastatin intervention group, losartan potassium combined with simvastatin intervention group, diabetes control group and normal control group. Six rats in each group were taken for 8 weeks and 12 weeks respectively. The levels of blood glucose, insulin, cardiac index and myocardial cell area were measured. The protein expressions of CTGF and TGF-β1 in myocardium were measured by immunohistochemistry. The mRNA levels of CTGF and TGF-β1 in myocardium were determined by PCR. Results The cardiac index and the area of cardiomyocytes in diabetic group were significantly increased (P <0.05). The expressions of CTGF and TGF-β1 mRNA and protein in myocardium were significantly increased in diabetic group (P <0.05) More obvious (P <0.05). Conclusion Both losartan potassium and simvastatin can inhibit the expression of CTGF and TGF-β1 in myocardium of diabetic rats and play a role of cardioprotection. The combination of the two drugs has synergistic effect.