金银花总黄酮对四氯化碳致大鼠肝纤维化的影响及机制

The effect and mechanism of Lonicera japonica total flavones on hepatic fibrosis induced by carbon tetrachloride in rats

目的探讨金银花总黄酮对由四氯化碳引起的大鼠肝纤维化的作用及机制。方法雄性SD大鼠随机分为正常对照组、模型组、金银花总黄酮低、高剂量组。40%CCl 4油溶液皮下注射诱导肝纤维化模型,检测各组血清中丙氨酸转氨酶(ALT)活性、羟脯氨酸(Hyp)含量及肝组织中丙二醛(MDA)含量、总超氧化物歧化酶(T-SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性,并通过HE染色观察肝组织形态学改变。培养大鼠肝星状细胞(HSC),采用MTT法和流式细胞技术,观察不同浓度的金银花总黄酮对HSC细胞株增殖及凋亡的影响。结果光镜下可观察到模型组大鼠肝细胞严重变性、坏死,胶原纤维明显增加;血清中ALT、Hyp含量升高,肝组织中MDA含量增高,T-SOD、GSH-Px活力显著下降。金银花总黄酮低、高剂量组与模型组比较,肝纤维化程度明显减轻,血清中ALT活性、Hyp含量及肝组织中MDA含量明显降低,T-SOD、GSH-Px活性明显升高。金银花总黄酮能不同程度的抑制HSC的增殖,促进其凋亡。结论金银花总黄酮对大鼠肝纤维化较好的防治作用,能降低肝纤维化程度,同时有效减轻肝细胞损伤,改善肝功能。

Objective:To study the effect and mechanism of Lonicera japonica total flavones(TFL)on liver fibrosis induced by carbon tetrachloride in rats.Methods:Male SD rats were randomly divided into normal control group,model group,low and high dose groups of TFL.The liver fibrosis model was induced by subcutaneous injection of 40%CCl4 oil solution.The activities of alanine aminotransferase(ALT),hydroxyproline(Hyp)in serum,and malondialdehyde(MDA),total superoxide dismutase(T-SOD),glutathione peroxidase(GSH-Px)in liver tissue were detected.And Morphological changes of liver tissue were observed by HE staining.Rat hepatic stellate cells(HSC)were cultured.MTT and flow cytometry was used to observe the effects of different concentrations of total flavonoids of TFL on proliferation and apoptosis of HSC.Results:Under light microscopy,severe degeneration and necrosis of hepatocytes and significant increase of collagen fibers were observed in the model group.The levels of ALT and Hyp in serum increased,MDA in liver tissue increased,and the activities of T-SOD and GSH-Px decreased significantly.TFL significantly reduced the degree of liver fibrosis,decreased the ALT activityand Hyp,MDA content,and significantly increased T-SOD,GSH-Px activity in model group.TFL could inhibit HSC proliferation and promote HSC apoptosis in varying degrees.Conclusion:TFL has a better preventive and therapeutic effect on liver fibrosis in rats,which can reduce the degree of liver fibrosis,effectively reduce the damage of hepatocytes and improve liver function.