防己黄芪汤对大鼠心肌纤维化的保护作用

The protective effect of Fangjihuangqi decoction on myocardial fibrosis in rats

目的:研究防己黄芪汤对心肌纤维化大鼠的保护作用及其机制。方法:48只SD大鼠随机分为6组:空白组、模型组、防己黄芪汤4.37g/kg组、防己黄芪汤8.73g/kg组、防己黄芪汤17.46g/kg组、卡托普利0.1g/kg组。模型组、防己黄芪汤各剂量组和卡托普利组大鼠采用皮下多点注射异丙肾上腺素5mg/(kg·d)连续7天,制备心肌纤维化模型,空白组大鼠注射等量生理盐水。造模后灌胃给药,4周后检测各组大鼠心脏血流动力学变化,计算心脏重量指数,HE染色及Masson染色观察心肌病理形态学变化。筛选防己黄芪汤最佳给药剂量并探索作用机制:用ELISA法测大鼠血浆中血管紧张素Ⅱ(AngⅡ)浓度,免疫组化法检测心肌中CollagenⅠ、CollagenⅢ的表达,Western-blot法检测p38MAPK、p-p38MAPK、TGF-β1的表达。结果:与模型组比较,防己黄芪汤8.73g/kg剂量组和防己黄芪汤17.46g/kg剂量组心肌功能明显改善,HWI、LVWI、CVF值均明显降低;防己黄芪汤4.37g/kg剂量组不能改善心肌功能,HWI、LVWI值与模型组比较无统计学差异,但一定程度上改善了病理损伤,CVF值较模型组明显降低。防己黄芪汤8.73g/kg组大鼠血浆AngⅡ水平和心肌组织中p38MAPK、p-p38MAPK、TGF-β1、CollagenⅠ、CollagenⅢ的表达较模型组均明显降低。结论:防己黄芪汤对心肌纤维化具有保护作用且8.73g/kg的剂量最佳,其可能机制是通过降低AngⅡ的水平来抑制p38MAPK的表达及其磷酸化,进而下调了TGF-β1的表达,使CollagenⅠ、CollagenⅢ合成减少。

Objective： To discuss the effect of Fangjihuangqi decoction on myocardial fibrosis and its mechanism of action. Methods：48 SD rats were randomly divided into 6 groups ： control group, model group, Fangjihuangqi decoction 4.37g/kg group, Fangjihuangqi decoction 8.73g/ kg group, Fangjihuangqi decoction 17.46g/kg group,captopril O. lg/kg group ,8 rats in each group. Model group, Fangjihuangqi decoction treatment group in each dosage and captopril 0. 1 g/kg group were given subcutaneous multi-point injection of isoproterenol 5mg/（ kg· d）for 7 days to become myocardial fibrosis rats, control group rats were injected with equivalent saline. Intragastric administration after modeled, 4 weeks later, cardiac hemodynamics change was tested , heart weight indexes were calculated, the changes of myocardial pathologic morpholo- gy were observed by HE and Masson staining. The concentrations of angiotensin II （ Ang II ） in plasma of rats were measured by ELISA, the expressions of Collagen I ,Collagen II were detected by Immunohistochemistry method, the expressions of p38MAPK, p-p38MAPK, TGF-β1 were detected by Western blottingmethod. Results： Compared with model group, the myocardial function were significantly improved and HWI, LVWI, CVF were significantly reduced in Fangjihuangqi decoction 8.73g/kg group and Fangjihuangqi decoction 17.46g/kg group（ P 〈 0. 01 ）but there was no statistic significance between these two groups（P 〉0.05） ; Fangjihuangqi decoction 4.37g/kg group can not improve myocardial function, the levels of HW], LVWI was no statistical difference compared with model group but it can improve pathological injury to a certain extent, CVF was reduced compared with model group（ P 〈 0.05）. Ang II levels in plasma and the expressions of p38MAPK, p- p38MAPK,TGF-β1 ,Collagen I ,Collagen III. were significantly reduced in Fangjihuangqi decoction 8.73g/kg group. Conclusion： Fangji- huangqi decoction can improve myocardial fibrosis and the effect of 8.73g/kg group was best. Its possible mechanism is to reduce Ang II lev- els to inhibit the expression of p38MAPK and its phosphorylation and then reduce the expression of TGF-β1, the synthesis of Collagen I and Collagen III will be reduced in the end.