五味子藤茎提取物抗大鼠肝纤维化作用及机制探讨

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目的:观察五味子藤茎提取物抗四氯化碳(CCl4)及乙醇所致肝纤维化的作用及机制。方法:50只Wistar大鼠随机分为正常组、模型组、五味子藤茎提取物高、中、低剂量组,采用ip CCl4,并饮用乙醇、饲用高脂饲料等复合因素制造肝纤维化模型,造模后,给药组分别ig高、中、低不同剂量(5.0,2.5,1.25 g·kg-1)五味子藤茎提取物,正常组和模型组灌服等量的生理盐水。末次给药后,检测血清丙氨酸转氨酶(ALT),天冬氨酸转氨酶(AST)活性,层粘蛋白(LN),透明质酸(HA),Ⅲ型前胶原(PCⅢ)水平,同时取大鼠肝组织,分别用于苏木素-伊红(HE)染色观察病理变化,蛋白质免疫印迹(Western blot)法检测转化生长因子-β_1(TGF-β_1),α-平滑肌肌动蛋白(α-SMA)蛋白表达水平。结果:与正常组比较,模型组大鼠血清AST,ALT活性及HA,LN,PCⅢ水平均显著升高,肝组织TGF-β_1,α-SMA蛋白表达水平显著增高(P<0.01);与模型组比较,五味子藤茎提取物能显著降低肝纤维化大鼠血清ALT,AST活性及HA,LN,PCⅢ水平,病理组织学检查结果显示,五味子藤茎提取物各剂量组大鼠肝组织结构明显改善,肝纤维化程度减轻,五味子藤茎提取物各剂量组均可显著降低肝组织TGF-β_1,α-SMA蛋白表达水平(P<0.01)。结论:五味子藤茎提取物对CCl4及乙醇所致肝损伤有明显保护作用,其机制可能与降低肝组织TGF-β_1,α-SMA蛋白表达、抑制肝星状细胞活化有关。 OBJECTIVE: To observe the effects and mechanisms of Schisandra cane extract on hepatic fibrosis induced by carbon tetrachloride (CCl4) and ethanol. Methods: Fifty Wistar rats were randomly divided into normal group, model group, high, medium and low dose of Schisandra cortex extract, using ip CCl4, drinking ethanol, feeding high fat diet and other factors to make liver fibrosis model After modeling, the rats in the treatment group were given high, medium and low doses of Schisandra sphenanthera extract (5.0,2.5,1.25 g · kg-1) respectively, and the normal group and model group were given the same amount of saline. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), laminin (LN), hyaluronic acid (HA) and procollagen Ⅲ were measured after the last administration. The rat liver tissues were stained for hematoxylin-eosin (HE) staining, and the pathological changes were observed. The expressions of TGF-β 1 (TGF-β 1), α-smooth muscle actin ) Protein expression level. Results: Compared with normal group, serum AST, ALT activity and HA, LN and PCⅢ levels in model group were significantly increased, while expression of TGF-β 1 and α-SMA in liver tissue were significantly increased (P <0.01) Compared with the control group, Schisandra cane extract could significantly reduce the serum ALT, AST activity and HA, LN, PCⅢ levels in liver fibrosis rats. The histopathological examination showed that the hepatic tissue structure of rats in each dose group was significantly (P <0.01). The levels of TGF-β 1 and α-SMA in hepatic tissue were significantly decreased in each dose group of Schisandra cane extract (P <0.01). Conclusion: The extract of Cynanchum Cuspidatum significantly protects against hepatic injury induced by CCl4 and ethanol. The mechanism may be related to the decrease of hepatic TGF-β1 and α-SMA protein expression and the inhibition of hepatic stellate cell activation.
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