大黄素对四氯化碳诱导肝纤维化大鼠的干预作用

Intervention effect of emodin on carbon tetrachloride-induced liver fibrosis in rats

目的探讨大黄素对四氯化碳诱导肝纤维化大鼠的干预作用。方法将50只SD大鼠随机分为正常组、模型组和大黄素低、中、高剂量组,每组10只。正常组给予常规饲养,大黄素各剂量组及模型组给予40%四氯化碳-橄榄油溶液腹腔注射8周以建立肝纤维化大鼠模型。于造模第5周起,大黄素低、中、高剂量组分别给予15 mg/kg、30 mg/kg、60 mg/kg的大黄素灌胃,模型组及正常组给予生理盐水灌胃,共4周。实验结束后,测定各组大鼠血清ALT、AST、白蛋白、透明质酸、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原水平;并检测肝组织结缔组织生长因子(CTGF)、金属蛋白酶组织抑制因子1(TIMP-1)、基质金属蛋白酶9(MMP)-9 mRNA的表达;肝组织经苏木精-伊红染色、Masson染色后观察病理学改变。结果模型组大鼠肝小叶结构破坏严重,可见不同程度纤维增生及大量胶原纤维增生;与模型组比较,各大黄素干预组大鼠肝细胞破坏、纤维增生性改变减轻。与正常组相比,模型组血清ALT、AST、透明质酸、LN、PCⅢ、Ⅳ型胶原水平以及肝组织CTGF、TIMP-1 mRNA表达水平升高,血清白蛋白以及肝组织MMP-9 mRNA表达水平降低(均P<0.05);与模型组大鼠相比,各大黄素干预组血清ALT、AST、透明质酸、LN、PCⅢ、Ⅳ型胶原水平以及肝组织CTGF、TIMP-1 mRNA表达水平降低,血清白蛋白以及肝组织MMP-9 mRNA表达水平升高(均P<0.05)。结论大黄素对四氯化碳诱导的肝纤维化大鼠有良好的治疗作用,其机制可能与抑制CTGF、TIMP-1的合成及促进MMP-9的表达有关。

Objective To investigate the intervention effect of emodin on carbon tetrachloride(CCl 4)-induced liver fibrosis in rats.Methods Fifty SD rats were randomly divided into normal group,model group,low-dose emodin group,moderate-dose emodin group and high-dose emodin group,with 10 rats in each group.Conventional feeding was performed on the normal group,the emodin groups and the model group were intraperitoneally injected with 40%CCl 4-olive oil solution for 8 weeks to develop a rat model of liver fibrosis.From the 5th week after modeling,the low-,moderate-and high-dose emodin groups were treated with 15 mg/kg,30 mg/kg and 60 mg/kg of emodin by intragastric gavage for 4 weeks,respectively,while the model group and the normal group were treated with normal saline by intragastric gavage for 4 weeks.At the end of the experiment,serum levels of ALT,AST,albumin,hyaluronic acid,laminin(LN),procollagen typeⅢ(PCⅢ)and collagen typeⅣwere detected in the rats of each group;the expression of connective tissue growth factor(CTGF),tissue inhibitor of metalloproteinases 1(TIMP-1)and matrix metalloprotein 9(MMP-9)mRNAs in liver tissues was determined;the histopathological changes in liver tissues were observed after hematoxylin-eosin staining and Masson staining.Results In the rats of the model group,the structure of hepatic lobule suffered from great damage,fibroplasia with various degrees and generous collagen fiber proliferation were observed;compared with the model group,the emodin groups presented alleviated hepatocyte destruction and reduced changes in fibroplasia.Compared with the normal group,the model group yielded increased levels of serum ALT,AST,hyaluronic acid,LN,PCⅢand collagen typeⅣ,higher expression levels of CTGF and TIMP-1 mRNAs in liver tissues,and lower serum albumin level and liver tissue MMP-9 mRNA expression level(all P<0.05);compared with the model group,the emodin groups exhibited decreased levels of serum ALT,AST,hyaluronic acid,LN,PCⅢand collagen typeⅣ,lower expression levels of CTGF and TIMP-1 mRNAs in liver tissues,and higher serum albumin level and liver tissue MMP-9 mRNA expression level(all P<0.05).Conclusion Emodin exerts a good therapeutic effect on CCl 4-induced liver fibrosis in rats,and the mechanism may be related to inhibition on synthesis of CTGF and TIMP-1 as well as promotion of MMP-9 expression.