镰形棘豆总黄酮灌胃对乙型肝炎大鼠肝损伤的改善作用及其机制  

Effect of total flavonoids of oxytropis falcate on liver injury rats with hepatitis B

作　　者：赵兴辉 叶柳凤 林小田 ZHAO Xinghui;YE Liufeng;LIN Xiaotian(The First Naval Hospital of Southern Theater Command,Zhanjiang 524000,China)

机构地区：[1]南部战区海军第一医院,广东湛江524000

出　　处：《山东医药》2020年第21期44-47,共4页Shandong Medical Journal

基　　金：湛江市第三批非资助科技攻关计划项目(2018B01129)。

摘　　要：目的观察镰形棘豆总黄酮灌胃对乙型肝炎(乙肝)大鼠肝损伤的改善作用,并探讨其作用机制。方法以乙肝病毒对大鼠进行尾静脉注射,建立乙肝大鼠模型。将乙肝模型大鼠随机分为模型组(生理盐水灌胃)、镰形棘豆总黄酮低剂量组(70 mg/kg的镰形棘豆总黄酮灌胃)、镰形棘豆总黄酮中剂量组(140 mg/kg的镰形棘豆总黄酮灌胃)、镰形棘豆总黄酮高剂量组(280 mg/kg的镰形棘豆总黄酮灌胃)、阿昔洛韦组(0.2 mg/kg的阿昔洛韦灌胃)各12只,以正常大鼠12只为对照组(生理盐水灌胃)。各组大鼠灌胃24 h后,取尾静脉血,采用ELISA试剂盒检测血清HBs Ag、HBe Ag,采用全自动生化分析仪测定血清ALT、AST。尾静脉取血后处死大鼠,解剖获得肝组织,HE染色后,观察肝组织病理形态。取大鼠肝组织,采用蛋白免疫印迹法检测各组大鼠肝组织纤维化相关蛋白及TGF-β/Smad3通路相关蛋白。结果与对照组相比,模型组大鼠血清HBs Ag、HBe Ag、ALT、AST水平明显升高(P均<0.05),肝组织出现肝小叶结构紊乱、肝细胞变性坏死、数量减少、肝组织局部坏死、有炎性细胞浸润及纤维结缔组织增生等病理损伤,大鼠肝组织纤维连接蛋白(FN)、四型胶原(Col IV)、TGF-β、p-Smad3/Smad3蛋白相对表达量明显升高(P均<0.05)。与模型组相比,镰形棘豆总黄酮低、中、高剂量组、阿昔洛韦组大鼠血清HBs Ag、HBe Ag、ALT、AST水平均降低(P均<0.05),且镰形棘豆总黄酮各剂量之间有剂量依赖性(P均<0.05),镰形棘豆总黄酮高剂量组与阿昔洛韦组差异无统计学意义(P均>0.05);大鼠肝组织病理损伤减轻;大鼠肝组织FN、Col IV、TGF-β、p-Smad3/Smad3蛋白相对表达量均降低(P均<0.05),且镰形棘豆总黄酮各剂量之间有剂量依赖性(P均<0.05),镰形棘豆总黄酮高剂量组与阿昔洛韦组差异无统计学意义(P均>0.05)。结论镰形棘豆总黄酮可改善乙肝大鼠肝组织损伤,抑制其纤维化,�Objective To observe the effect of the total flavonoids of oxytropis falcate on liver injury rats with hepatitis B(hepatitis B),and to explore its mechanism.Methods Hepatitis B virus was injected into the tail vein of rats to establish the model of hepatitis B.The hepatitis B model rats were randomly divided into the model group(normal saline gavage),low-dose(70 mg/kg),medium-dose(140 mg/kg),high-dose oxytropis falcate total flavonoids groups(280 mg/kg),and acyclovir group(0.2 mg/kg acyclovir),with 12 in each,meanwhile,12 normal rats were treated as control group(normal saline gavage).The rats in each group were given gavage for 24 h,tail venous blood was taken,the serum HBs Ag and HBe Ag were detected by ELISA kit,and serum levels of ALT and AST were determined by automatic biochemical analyzer.After taking blood from tail vein,the rats were sacrificed and liver tissues were dissected;after HE staining,the pathological morphology of liver tissues was observed.The liver tissue of rats was taken,and the hepatic fibrosis-related proteins and TGF-β/Smad3 pathway were detected by Western blotting.Results Compared with the control group,the serum levels of HBs Ag,HBe Ag,ALT and AST in the model group increased significantly(all P<0.05),with disordered hepatic lobules in liver tissues,less hepatocytes and degeneration and necrosis,local necrosis of liver tissue,inflammatory cell infiltration and hyperplasia of fibrous connective tissues and other pathological injuries;the relative expression levels of fibronectin(FN),type IV collagen(Col IV),TGF-βand p-Smad3/Smad3 in the rat liver tissues increased significantly(all P<0.05).Compared with the model group,serum HBs Ag,HBe Ag,ALT and AST levels of rats all decreased in the lowdose,medium-dose and high-dose groups and acyclovir group,with a dose-dependent manner(all P<0.05),and there was no significant difference between the high-dose oxytropis falcate total flavonoids group(all P>0.05);the pathological damage of rat liver tissues was alleviated;the relative expression l

关 键 词：镰形棘豆总黄酮 乙型肝炎 纤维连接蛋白 四型胶原 TGF-β/Smad3通路 动物实验 

分 类 号：R285.5[医药卫生—中药学]