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目的研究不同血管紧张素受体阻滞剂(ARBs)对糖尿病心肌纤维化的影响。方法将50只SD大鼠随机分为正常组(n=10)和糖尿病组(n=40),糖尿病组使用腹腔注射链脲佐菌素(STZ)方法建立糖尿病大鼠模型。将建模成功后36只大鼠随机分为三组:糖尿病模型组(10只)、氯沙坦治疗组(13只)和替米沙坦治疗组(13只)。采用免疫组化法检测各组大鼠心肌组织Ⅰ、Ⅲ型胶原、转化生长因子β1(TGF-β1)、结缔组织生长因子(CTGF)表达。计算每组的心脏指数和左心室指数;采取放免法测定心肌组织AngⅡ的含量。各组数据以均数±标准差(x±s)表示,组间比较采用方差分析、t检验,P<0.05为差异有统计学意义。结果糖尿病大鼠模型组的心脏指数、左心室指数、Ⅰ型胶原和Ⅲ型胶原、AngⅡ、TGF-β1、CTGF均分别显著高于正常组的(均P<0.05);与糖尿病模型组相比,氯沙坦治疗组和替米沙坦治疗组上述各指标均有明显降低(均P<0.05),但氯沙坦治疗组和替米沙坦治疗组之间差异均无统计学意义(P>0.05)。结论氯沙坦、替米沙坦均可明显抑制糖尿病心肌纤维化的发病过程。
Objective To investigate the effects of different angiotensin receptor blockers (ARBs) on diabetic myocardial fibrosis. Methods Fifty SD rats were randomly divided into normal group (n = 10) and diabetic group (n = 40). Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ). Thirty-six rats were randomly divided into three groups: diabetic model group (n = 10), losartan treatment group (n = 13) and telmisartan treatment group (n = 13). Immunohistochemistry was used to detect the expression of collagen type Ⅰ, Ⅲ, transforming growth factor β1 (TGF-β1) and connective tissue growth factor (CTGF) in myocardium of rats in each group. The cardiac index and left ventricular index of each group were calculated. The content of AngⅡ in myocardial tissue was determined by radioimmunoassay. Data of each group were expressed as mean ± standard deviation (x ± s), between groups were analyzed by analysis of variance and t test, P <0.05 for the difference was statistically significant. Results The cardiac index, left ventricular index, collagen type Ⅰ and type Ⅲ collagen, AngⅡ, TGF-β1 and CTGF in model group were significantly higher than those in normal group (all P <0.05). Compared with diabetic model group , Losartan and Telmisartan treatment groups were significantly lower (P <0.05, respectively), but the losartan treatment group and telmisartan treatment group differences were not statistically significant (P > 0.05). Conclusion Losartan and telmisartan can significantly inhibit the pathogenesis of diabetic myocardial fibrosis.