用苹果辅助逆转大鼠肝纤维化的实验性研究

Adjuvant reverse effect of apple on liver fibrosis in rats

目的:研究苹果对实验性肝纤维化大鼠的辅助逆转作用,并探讨其对肝纤维化的影响机制。方法:雄性SD大鼠42只分为正常组、CCl4肝纤维化模型组、自然恢复组、丹芍化纤治疗组、丹芍化纤+苹果试验组。除正常组以外,其余大鼠均采用CCl4、饮酒、高脂低蛋白饮食等复合因素刺激制备大鼠肝纤维化模型共8周。确认造模成功后再将剩余模型组大鼠随机分为丹芍化纤+苹果试验组、丹芍化纤治疗组及自然恢复组,共观察8周。结果:丹芍化纤+苹果试验组与模型组、自然恢复组及丹芍化纤治疗组比较:肝脏指数、血清ALT及AST显著下降(P<0.05,P<0.01,P<0.01);RT-PCR中核因子相关因子2(NF-E2-relatedfactor 2,Nrf-2)mRNA及血红素加氧酶-1(Heme oxygenase-1,HO-1)mRNA在丹芍化纤+苹果试验组中的表达较丹芍化纤治疗组与模型组、自然恢复组升高(P<0.05),丹芍化纤+苹果试验组中肝组织TGF-β1的表达较丹芍化纤治疗组与模型组、自然恢复组降低(P<0.05)、而MMP-2在丹芍化纤+苹果试验组中的表达较丹芍化纤治疗组与模型组、自然恢复组升高(P<0.05);GSH有所升高,MDA有所降低,差异有统计学意义(P<0.05)。结论:苹果在实验性肝纤维化大鼠的逆转过程中起到了有效的辅助作用,辅助逆转的机制可能与其上调Nrf-2表达,从而增强HO-1表达,增强其抗氧化功能,抑制脂质过氧化作用在丹芍化纤胶囊的治疗基础上进一步抑制了TGF-β1的表达;从而促进细胞外基质的降解,这可能是苹果辅助逆转肝纤维化的机制之一。

Objective：To study the beneficial effects of apple as an adjuvant on liver fibrosis in rats and to explore its potential mechanisms.Methods： Forty two SD rats were divided into the normal（n=10）,fibrosis model control（n=8）,Danshao Huaxian（DHC）（n=8）,DHC plus Apple（n=8） and model（n=8） groups.Liver fibrosis model was induced by complex etiological factors,including CCl4,alcohol（every other day）and high lipid,low protein diets for eight weeks.After the establishment of liver fibrosis,model rats were treated with DHC and DHC plus Apple.The degree of liver fibrosis was examined under microscope.the liver index.Results： ALT and AST were significantly decreased in DHC plus Apple group（P0.01,P0.01,P0.01）.GSH of liver homogenate in DHC plus Apple group was signifi cantly higher and MDA was lower than those in the DHC and model control groups（P0.05）.Hepatic mRNA expression of TGF β1 was significantly decreased（P0.05）,while the expre-ssions of MMP 2 Nrf2 and HO 1 were significantly increased compared to model control,DHC and Apple alone groups（P0.05）.Conclusion： Apple has beneficial effects as an adjuvant in the treatment of liver fibrosis when used together with DHC in rats.The mechanisms of apple as an adjuvant in reversing the rats liver fibrosis seems to up modulate the expression of Nrf-2 while promote the HO 1 expression and amplify anti-oxidize reaction.These effects appear to be related to promoting the degradation of extracellular base by induction of MMP,and by suppression of TGF β1 expression.