双氢青蒿素对肝纤维化小鼠TGF-β1和TNF-α的影响

Effects of dihydroartemisinin on TGF-β1 and TNF-α in mice with hepatic fibrosis

目的探讨双氢青蒿素(DHA)对四氯化碳诱导的肝纤维化小鼠肝组织中转化生长因子-β1(TGF-β1)和肿瘤坏死因子(TNF-α)的含量的变化。方法实验小鼠随机分成对照组、纤维化组和DHA干预组3组,通过向腹腔注射四氯化碳建立小鼠肝纤维化模型。DHA干预组口服DHA;对照组、纤维化组均口服等剂量的含二甲基亚砜的生理盐水。各组的肝组织切片经苏木素-伊红染色和天狼猩红染色法观察其形态结构变化;生物化学分析法检测各组小鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)的含量。ELISA测定肝组织中TGF-β1和TNF-α的含量。结果观察各组苏木素-伊红染色和天狼猩红染色后肝组织的形态结构表明肝纤维化动物模型的成功建立。纤维化组小鼠肝内肝细胞坏死,汇管区纤维组织和胆总管明显增生,血清中ALT[(142.9523±23.7624)U/L]和AST[(177.5611±15.5477)U/L]含量增加,肝组织中TGF-β1[(34.1211±3.0912)μg/L]和TNF-α[(48.6753±4.2213)ng/L]的含量升高,与对照组相比,差异均有统计学意义(均P<0.05)。经过DHA治疗后小鼠肝内肝组织坏死减少,肝内纤维组织增生降低,血清中ALT[(87.6745±16.5461)U/L]、AST[(127.6443±21.3452)U/L]含量减少,肝组织中TGF-β1[(25.9011±3.5671)μg/L]和TNF-α[(38.6651±3.9065)ng/L]的含量降低,与对照组相比差异均有统计学意义(均P<0.05)。结论DHA可以拮抗小鼠肝纤维化,是通过减少小鼠肝组织中的TGF-β1和TNF-α的含量来发挥作用的。

Objective To explore the effects of dihydroartemisinin(DHA)on the contents of transforming growth factor-beta 1(TGF-β1)and tumor necrosis factor(TNF-α)in liver tissue of mice with carbon tetrachloride-induced liver fibrosis.Methods The experimental mice were randomly divided into 3 groups:normal group,model group and DHA intervention group.The liver fibrosis model of mice was established by intraperitoneal injection of carbon tetrachloride.The DHA intervention group was given dihydroartemisinin orally,while the normal group and the model group were given normal saline containing dimethyl sulfoxide at the same dose.The morphological changes of liver tissue sections were observed by hematoxylin-eosin staining and Sirius red staining.The contents of alanine aminotransferase(ALT)and glutamic oxaloacetate transaminase(AST)in serum were evaluated by biochemical analysis.The contents of TGF-β1 and TNF-αin liver tissue were determined by ELISA.Results The morphological structure of liver tissue after hematoxylin-eosin staining and Sirius red staining in each group showed that the animal model of liver fibrosis was successfully established.Focal necrosis appeared in the liver,fibrous tissue and common bile duct in portal area increased significantly,the contents of ALT[(142.9523±23.7624)U/L]and AST[(177.5611±15.5477 U/L)]in serum increased,and the contents of TGF-β1[(34.1211±3.0912)μg/L]and TNF-α[(48.6753±4.2213)ng/L]in liver tissue increased in the model group,which were significantly different from those in the normal group(all P<0.05).After intervention with DHA,the necrosis of liver tissue and proliferation of fibrous tissue in liver decreased,the contents of ALT[(87.6745±16.5461)U/L]and AST([127.6443±21.3452)U/L]in serum decreased,and the contents of TGF-β1[(25.9011±3.5671)μg/L]and TNF-α[(38.6651±3.9065)ng/L]in liver tissue decreased,which had statistical significance compared with the normal group(all P<0.05).Conclusion DHA can antagonize liver fibrosis in mice by reducing the contents of TGF-β1 and TNF-αin liver tissue.