葛根素对异丙肾上腺素诱导的小鼠心肌纤维化的防治作用及机制探讨

摘要

Objective To investigate the protective effect of puerarin on isoprenaline( ISO)-induced myocardial fibro-aia ( MF)in mice and its mechanism. Methods Fifty mice were randomly divided into 5 groups with 10 in each, the control group, the myocardial fibroais model group, puerarin low dosage group, puerarin high dosage group and captopril group. Thepuerarin low dosage group, puerarin high dosage group and captopril group were given puerarin of 600, 1 200 mg/kg and captopril of 25 rag/kg by gastric perfusion for 3 days; the control group was given puerarin solventfor 3 days. Then the five groups were all given ISO for 30 days to make MF model. Finally, the cardiac weight index (CWI) was calculated; hydroxyproh'ne( Hydro)level in myocardium was determined by a colorimetric method; Massons trichrome staining was used to estimate the collagen content; the collagen volume fraction (CVF) was determined; RT-PCR was used to measure the mRNA expression of matrix metalloprateinase-2( MMP-2) and MMP-9; immunohistochemistry was used to measure the protein expression of MMP-9. Results Compared with the model group, CWI, Hydro level and CVF in puerarin low and high dosage groups decreased obviously; the mRNA expressions of MMP-2 and MMP-9 increased obviously; the protein expression of MMP-9 significantly increased (all P <0. 05). Conclusion Puerarin can prevent the ISO-induced MF in mice, and its mechanism might be related to the increment of MMP-2 and MMP-9 expressions.%目的 探讨葛根素对异丙肾上腺素诱导的小鼠心肌纤维化(MF)的防治作用及机制.方法 将50只昆明小鼠分为对照组,模型组,葛根素低、高剂量组和卡托普利组各10只.葛根素低、高剂量组和卡托普利组预先分别予葛根素600、1200 mg/kg及卡托普利25 mg/kg灌胃给药3d；对照组予葛根素溶媒灌胃3d.给药后五组同时皮下注射异丙肾上腺素30 d制作MF模型.观察各组心重指数(CWI)；消化法测定心肌羟脯氨酸(Hydro)含量；计算心肌胶原容积分数(CvF)；采用RT-PCR法观察心肌MMP-2、MMP-9 mRNA表达；采用免疫组化法观察心肌MMP-9蛋白表达.结果 与模型组比较,葛根素低、高剂量组CWI和Hydro含量明显降低；心肌细胞间胶原含量明显减少,CVF明显下降；心肌MMP-2及MMP-9 mRNA表达明显升高；MMP-9蛋白表达明显升高(P均＜0.05).结论 葛根素对异丙肾上腺素诱导的小鼠MF有一定预防及治疗作用,其机制可能与增加心肌MMP-2及MMP-9表达有关.