蒙古扁桃不同极性部位对肝纤维化大鼠的保护作用及机制研究

吴桐; 周红兵; 王佳; 常虹; 白万富; 权博文; 郝海梅; 白迎春; 石松利

doi:10.13386/j.issn1002-0306.2020090212

蒙古扁桃不同极性部位对肝纤维化大鼠的保护作用及机制研究

Effect of Different Solvent Extracts of Amygdalus mongolica on Liver Fibrosis Rat Models Induced by Carbon Tetrachloride and Its Mechanisms

摘要

摘要: 探讨蒙古扁桃不同极性部位对四氯化碳致肝纤维化大鼠的作用及可能机制。雄性SD大鼠分为7组，每组10只。以四氯化碳建立肝纤维化大鼠模型，将成模大鼠分为模型组、水飞蓟素组(0.05 g/kg)阳性药组和蒙古扁桃石油醚、乙酸乙酯、正丁醇、水部位提取物组，同批未给四氯化碳的大鼠为正常对照组。给药8周后，测血清中的丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase，AST）、碱性磷酸酶（alkaline phosphatase，ALP）活性及丙二醛（malondialdehyde，MDA）、超氧化物歧化酶（superoxide dismutase，SOD）、透明质酸（hyaluronic acid， HA）、层粘连蛋白（laminin，LN）、Ⅲ型前胶原（type Ⅲ collagen，PC-Ⅲ）和Ⅳ型胶原（type Ⅳ collagen ，Col-Ⅳ）含量并计算肝指数和脾指数；同时测肝组织中MDA、SOD、羟脯氨酸（hydroxyproline，HYP）含量及转化生成因子β1（Transforming growth factor β1 protein，TGF-β1）、Smad3（mothers against decapentaplegic homolog）和Smad7的表达。与模型组比较，蒙古扁桃药材各极性部位大鼠的体质量显著增加（P<0.05），血清和组织中MDA显著降低（P<0.05），血清中SOD显著升高（P<0.05），石油醚、水部位大鼠肝指数显著降低（P<0.05）；病理学检查结果显示，蒙古扁桃药材各部位给药组大鼠肝纤维化有明显改善；蒙古扁桃石油醚部位和正丁醇部位可显著降低血清中AST、ALP、HA、PC-Ⅲ含量（P<0.05）及下调组织中HYP、TGF-β1和Smad3的水平（P<0.05）；蒙古扁桃正丁醇部位可显著降低血清中ALT含量（P<0.05）。蒙古扁桃药材石油醚、正丁醇提取物对肝纤维化有显著改善作用，是保护肝纤维化的优选活性部位，其机制可能是通过调节胶原合成异常及TGF-β1/Smad 信号通路来发挥作用。

Abstract: To investigate the effects and possible mechanisms of different polarity positions of Amygdalus mongolica on carbon tetrachloride to hepatic fibrosis rats. Male SD rats were divided into 7 groups with 10 in each group. The rats were divided into model group, silymarin group (0.05 g/kg), positive drug group and Amygdalus mongolica petroleum ether, ethyl acetate, n-butanol and aqueous extract group. The rats in the same group were not given carbon tetrachloride as normal control group. After 8 weeks of treatment, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activity and malondialdehyde (MDA), superoxide dismutase (SOD), hyaluronic acid (HA), laminin (LN), type Ⅲ collagen (PC-Ⅲ) and type Ⅳ collagen (Col-Ⅳ) content were measureed, and the liver index and spleen index were calculated; The contents of MDA, SOD and Hydroxyproline(HYP) and the expressions of transforming growth factor β1 protein (TGF-β1), mothers against decapentaplegic homolog 3 (Smad3) and Smad7 mRNA in liver tissues were also measured. Compared with the model group, the body mass of the rats in various polar parts of Amygdalus mongolica significantly increased (P<0.05), MDA in serum and tissues significantly decreased (P<0.05), SOD in serum significantly increased (P<0.05), and liver index of the rats in petroleum ether and water parts significantly decreased (P<0.05). The results of pathological examination showed that the liver fibrosis of the rats in each part of the drug group was significantly improved. Amygdalus mongolica petroleum ether part and n-butanol part could significantly decrease in the serum AST, ALP, HA, PC-Ⅲ content (P<0.05), HYP, TGF-β1 and Smad3 levels in the organization (P<0.05). The n-butanol position of Amygdalus mongolica could significantly reduce the serum ALT level (P<0.05). Amygdalus mongolica herbs petroleum ether, n-butanol extract has improved markedly effect to liver fibrosis, which is the preferred active site for protection of liver fibrosis and its mechanism may be through adjusting abnormal collagen synthesis and TGF-β1 / Smad signaling pathways to work.