厄贝沙坦对抗糖尿病大鼠心肌纤维化作用及机制

目的：观察厄贝沙坦对抗糖尿病大鼠心肌纤维化的作用，并分析细胞外调节信号激酶（ERK）通路在其中的作用。方法：健康雄性SD大鼠32只，随机分成两组：正常对照组（CON，n=10），实验组（n=22）。实验组糖尿病造模成功20只，随机分为2组（n=10）：糖尿病组（DM）、厄贝沙坦+糖尿病组（Ir+DM）。8周后测定空腹血糖（FBG）水平，计算各组大鼠体重（BW）、心体比（H/B）和左室重量指数（LVWI）；Masson染色观察心肌形态及纤维化的发生；ELISA检测心肌组织胶原Ⅰ（colⅠ）、胶原Ⅲ（colⅢ）含量；Western blot检测心肌组织ERK1/2、p-ERK1/2蛋白的表达。结果：与CON组相比，DM组大鼠FBG水平、H/B、LVWI显著升高，体重显著减轻，colⅠ、colⅢ含量显著增加，心肌组织p-ERK1/2蛋白表达及p-ERK1/2/ERK1/2比值增加（P<0.05，P<0.01），ERK1/2无明显变化。Masson染色显示DM组心肌胶原纤维粗大，交织成网状，排列分布不均，沉积增多。与DM组大鼠相比，厄贝沙坦干预后大鼠体重明显增加，H/B、LVWI、心肌组织colⅠ、colⅢ含量明显降低（P<0.05，P<0.01），p-ERK1/2蛋白表达及p-ERK1/2/ERK1/2比值降低（P<0.01），且心肌形态改善明显。结论：糖尿病可诱导心肌纤维化的发生，厄贝沙坦可通过抑制ERK的活化减轻糖尿病诱导的心肌纤维化损伤。

The mechanism of irbesartan against diabetes induced myocardial fibrosis in rat model

Objective:To observe the protective effect of irbesartan on myocardial fibrosis in diabetic rats, and analyze the role of extracellular signal-regulated kinase (ERK) pathway in this protection. Methods:Thirty two male SD rats were randomly divided into two groups:normal control group (CON, n=10), experimental group (n=22). Twenty diabetic rats which had modelled successfully were randomly divided into two groups:diabetic group (DM, n=10), irbesartan + DM group (Ir+DM, n=10). After 8 weeks, fasting blood glucose (FBG) level, body weight (BW), the ratio of heart weight/body weight (H/B) and left ventricular weight index (LVWI) were measured. The myocardial morphological and fibrotic changes were observed by Masson staining. Col I and col Ⅲ contents were evaluated using ELISA method, and the protein expressions of ERK1/2, p-ERK1/2 in heart tissue were tested by Western blot. Results:Compared with CON group, in diabetic rats, the levels of FBG, H/B and LVWI were increased while BW was decreased. The contents of col I and col Ⅲ were increased as well as the protein expression of p-ERK1/2 and the ratio of p-ERK1/2/ERK1/2(P<0.05,P<0.01), which had the statistic differences, while ERK1/2 protein expression was not changed. Masson staining showed myocardial collagen was increased, arranged in disorder and uneven distribution. However, in Ir+ DM group, BW was increased obviously, H/B, LVWI, the contents of col I and col Ⅲ were decreased significantly (P<0.05,P<0.01), p-ERK1/2 protein expression and the ratio of p-ERK1/2/ERK1/2 were decreased (P<0.01), which had the statistic differences. Meanwhile myocardial morphology was improved significantly. Conclusion:Diabetes can induce the happening of myocardial fibrosis, and irbesartan can induce the damage of myocardial fibrosis through inhibitting the activation of ERK.