中文摘要：

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。

英文摘要：

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.