厄贝沙坦对大鼠梗死心肌组织中HGF mRNA和蛋白水平的影响

目的:通过观察厄贝沙坦对大鼠心肌梗死模型中缺血心肌肝细胞生长因子(HGF)mRNA和蛋白水平的影响,探讨厄贝沙坦减轻心肌纤维化的可能机制。方法:采用雄性Wistar大鼠建立心肌梗死模型,术后24 h将存活大鼠随机分为模型组和厄贝沙坦组,另设假手术组,每组9只大鼠。厄贝沙坦组予以厄贝沙坦50 mg·kg-1·d-1灌胃,模型组及假手术组给予等体积生理盐水灌胃,每天1次。4周后心脏取材,测量各组大鼠体重及左室重量,HE染色法观察缺血心肌病理改变,RT-q PCR和Western blot法检测各组大鼠心肌组织中HGF mRNA及蛋白水平的表达。结果:HE染色可见假手术组心肌细胞排列整齐,模型组及厄贝沙坦组心肌结构紊乱,药物组病理改变较模型组减轻;4周后各组大鼠体重无显著差异,各组间左心室重量差异有统计学意义(P0.01),厄贝沙坦组及模型组左室重量高于假手术组(P0.05),同时厄贝沙坦组低于模型组(P0.05);各组大鼠心肌组织中均检测到HGF的mRNA及蛋白水平,厄贝沙坦组及模型组HGF的mRNA与蛋白含量均高于假手术组(P0.05),厄贝沙坦组HGF的mRNA与蛋白水平低于模型组(P0.05)。结论:心肌梗死模型大鼠应用厄贝沙坦治疗4周时左室重量明显减轻,心肌组织病理变化得到改善,心肌组织中HGF的mRNA与蛋白水平降低。

Effects of irbesartan on expression of HGF at mRNA and protein levels in rats with myocardium infarction

AIM: To investigate the effects of irbesartan on the expression of hepatocyte growth factor (HGF) at mRNA and protein levels in rats with myocardial infarction (MI), and to explore the mechanisms of irbesartan attenuating myocardial fibrosis.METHODS: The male Wistar rat model of MI was successfully established. The surviving rats 24 h after the operation were randomly divided into 3 groups:model group, irbesartan group and sham group, with 9 rats in each group. The rats in irbesartan group were treated with the solution of irbesartan (50 mg·kg^-1·d^-1) by intragastric administration, while the rats in model group and sham group received the equal volume of saline by the same way. The body weight and left ventricle mass (LVM) of the rats were measured at the 4th week after operation, and the pathological changes of the ischemic myocardium were observed with HE staining. Meanwhile, the expression of HGF at mRNA and protein levels was detected by RT-qPCR and Western blot.RESULTS: HE staining showed that the myocardial cells in sham group were in neat arrangement, while the cardiac structure in model group and irbesartan group was in disorder. The pathological changes in irbesartan group were less than that in model group. No difference in the body weight at the 4th week after operation was observed, while the LVM was significantly different among the 3 groups (P<0.01). The LVM in model group was higher than that in sham group (P<0.01), and that in irbesartan group was higher than that in sham group (P<0.05). The LVM in irbesartan group was lower than that in model group (P<0.05). The expression of HGF at mRNA and protein levels was detected in each group. The expression of HGF at mRNA and protein levels in irbesartan group was higher than that in sham group (P<0.05), and that in model group was higher than that in sham group (P<0.01). Moreover, the mRNA and protein levels of HGF in irbesartan group were lower than those in model group (P<0.05).CONCLUSION: The LVM of MI rats with the treatment of irbesartan was reduced obviously at the 4th week after operation, and the pathological changes were also improved. At the 4th week after the operation, the treatment of irbesartan inhibited the expression of HGF at mRNA and protein levels.