水飞蓟宾对硫代乙酰胺诱导的肝纤维化大鼠TGF-β1/Smad3信号通路的调节作用  

Regulatory effect of silybin on TGF-β1/Smad3 signal pathway in rats with hepatic fibrosis induced by thioacetamide

作　　者：李燕菊[1,2] 冯杰 韩忠诚[3] 赵婷 李红健[1,2] 马俊鹏[1] 孙力玛尔江·巴哈提别克 王燕[1,2] 于鲁海 LI Yanju;FENG Jie;HAN Zhongcheng;ZHAO Ting;LI Hongjian;MA Junpeng;SUN Li;MARJAN Bahatibek;WANG Yan;YU Luhai(Department of Pharmacy, The People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China;Xinjiang Uygur Autonomous Region Institute of Clinical Pharmacy, Urumqi 830001, China;Department of Oncology, The People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China)

机构地区：[1]新疆维吾尔自治区人民医院药学部,新疆乌鲁木齐830001 [2]新疆维吾尔自治区临床药学研究所,新疆乌鲁木齐830001 [3]新疆维吾尔自治区人民医院肿瘤科,新疆乌鲁木齐830001

出　　处：《西部医学》2021年第8期1150-1154,共5页Medical Journal of West China

基　　金：新疆维吾尔自治区自然科学基金(2020D01C100)。

摘　　要：目的探讨水飞蓟宾对硫代乙酰胺(TAA)诱导的肝纤维化大鼠肝组织的保护作用及对TGF-β1/Smad3信号通路的调节作用。方法45只大鼠按照随机数字表法分为对照组、模型组及水飞蓟宾组,每组15只。除对照组外,其余大鼠使用硫代乙酰胺建立肝纤维化大鼠模型,水飞蓟宾组大鼠按照75.6 mg/kg的剂量给予水飞蓟宾灌胃,对照组及模型组大鼠给予等量生理盐水灌胃,1次/d,给药6周。全自动生化分析仪检测大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(GGT)水平,酶联免疫吸附(ELISA)法检测血清透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)及Ⅳ型胶原蛋白(ColⅣ)水平,苏木精-伊红(HE)染色法检测各组大鼠肝组织病理学变化,免疫印迹(Western blot)检测大鼠肝组织TGF-β1、Smad3水平。结果与对照组比较,模型组肝纤维化大鼠血清ALT、AST、ALP、GGT、HA、LN、PCⅢ、ColⅣ水平及肝组织TGF-β1、Smad3水平显著升高(均P<0.05),肝组织发生明显病理学变化;与模型组比较,水飞蓟宾组大鼠血清ALT、AST、ALP、GGT、HA、LN、PCⅢ、ColⅣ水平及肝组织TGF-β1、Smad3水平显著降低(均P<0.05),肝组织病理学明显改善。结论水飞蓟宾能够明显改善硫代乙酰胺诱导的肝纤维化大鼠肝功能,抑制肝纤维化因子水平,改善大鼠肝组织病理学进展,其机制可能与调节TGF-β1/Smad3信号通路有关。Objective To study the protective effect of silybin on liver tissue and regulation of TGF-β1/Smad3 signal pathway in thioacetamide-induced hepatic fibrosis in rats.Methods 45 rats were randomly divided into control group,model group,silybin group and colchicine group,with 15 rats in each group.Except for the control group,the other rats were treated with thioacetamide to establish the rat model of hepatic fibrosis.The rats in the silybin group were given silibinin according to the dose of 75.6mg/kg.The rats in the control group and model group were given the same amount of normal saline once a day for 6 weeks.The levels of ALT,AST,ALP and GGT in serum were detected by automatic biochemical analyzer,and the levels of HA,LN,PCⅢand ColⅣin serum were detected by ELISA method.The pathological changes of liver tissue were detected by hematoxylin-eosin(HE)staining,and the levels of TGF-β1 and Smad3 in liver tissue were detected by,western blot.Results The serum levels of ALT,AST,ALP,GGT,HA,LN,PCⅢ,ColⅣand the levels of TGF-β1 and Smad3 in the liver tissue of the model group were significantly higher than those of the control group(P<0.05),and obvious pathological changes occurred in the liver tissue of the model group.Compared with the model group,the serum levels of ALT,AST,ALP,GGT,HA,LN,PCⅢ,ColⅣand the levels of TGF-β1 and Smad3 in liver tissue of rats in silybin group were significantly decreased(P<0.05),and the liver histopathology was significantly improved.Conclusion silybin can significantly improve the liver function of thioacetamide-induced hepatic fibrosis in rats,inhibit the level of hepatic fibrosis factors,and improve the pathological progress of liver tissue in rats.The mechanism may be related to the regulation of TGF-β1/Smad3 signal pathway.

关 键 词：水飞蓟宾 肝纤维化 TGF-β1/Smad3信号通路 硫代乙酰胺 

分 类 号：R575.2[医药卫生—消化系统]