湖北海棠叶总黄酮抗CCl4所致大鼠肝纤维化作用研究

目的:研究湖北海棠叶总黄酮对四氯化碳(CCl4)所诱导的大鼠肝纤维化的影响,并探讨其可能的作用机制。方法:腹腔注射2ml/kg CCl4橄榄油溶液制备大鼠肝纤维化模型。首次注射后分别灌胃给药湖北海棠叶总黄酮120mg/kg和60mg/kg,每天一次,共8周。测定血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、透明质酸、羟脯氨酸、β1-转化生长因子以及肝组织中总抗氧化能力、丙二醛含量和总超氧化物歧化酶的活性;用免疫组化方法定量肝组织中α-平滑肌肌动蛋白的表达。结果:与模型组比较,湖北海棠叶总黄酮能够调低血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、透明质酸、羟脯氨酸、β1-转化生长因子含量,降低肝组织丙二醛含量,增加肝组织中总抗氧化能力和总超氧化物歧化酶活性,降低α-平滑肌肌动蛋白的表达;病理学切片显示湖北海棠叶总黄酮能明显减轻CCl4引起的大鼠肝损伤及纤维化程度。结论:湖北海棠叶总黄酮在实验的120mg/kg和60mg/kg两个剂量组对CCl4致大鼠肝纤维化都有防治作用,作用机制可能与其抗氧化作用有关,湖北海棠叶总黄酮能能增强组织抗氧化能力,降低CCl4引起的脂类过氧化,保护细胞膜免受损伤,抑制β1-转化生长因子等具有加重肝纤维化程度的生物因子的表达,减轻肝纤维化程度。

Inhibitory action of total flavonoids of Malus hupehensis on hepatic fibrosis induced by CCl4 in rats

Objective: To investigate the effect of total flavonoids of Malus hupehensis and its mechanism of action on hepatic fibrosis in rats induced by carbon tetrachloride(CCl4).Method: The rats model of hepatic fibrosis which induced by injecting CCl4 intraperitoneal were randomly divided into 5 groups of 10 mice per group: group A injected with olive oil served as blank control;group B as model;group C was positive control treated with colchine,group D,E were treated by oral administration high dose 120mg/kg,low dose 60 mg/kg of total flavonoids of Malus hupehensis twice a week at the same time;Group A and B were orally given by Sodium Chloride as contol.All the rats were killed at the end of administration.Serum hyaluronic acid(HA),transforming growth factor-β1(TGF-β1),alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected;hydroxyproline(Hyp)、 malondialdehyde(MDA),total-antioxygen capacity(T-AOC) and total-superoxide dismutase(T-SOD) in liver tissue were detected;area of liver injury and degree of hepatic fibrosis were observed via HE and Masson stainings;alpha-smooth muscle actin(α-SMA) was deected by immunohistochemistry.Results: Comparing with the model group,the level of HA,TGF-β1,ALT and AST in blood serum and Hyp in liver tissues in high and low dose group of total flavonoids were significantly lower,the total flavonoids degraded MDA and increase the activity of T-AOC and T-SOD in liver tissues;the area of liver injury,the collagen deposit and the degree of hepatic fibrosis in group D,E were significantly lower than the model group B.Conclusion: The total flavonoids of Malus hupehensis had an obvious inhibitory action on the hepatic fibrosis induced by CCl4,hepatoprotective effects of total flavonoids of Malus hupehensis may be related to its antioxidant characteristic.Total flavonoids of Malus hupehensis could enhance the antioxidant capacity of organizations,reduce the level of lipid peroxidation induced by CCl4,and protect cellmembranes from damage,and have an inhibition of TGF-β1 which could aggravate the hepatic fibrosis expression in liver to reduce the degree of liver fibrosis.