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葛根-南五味子预防给药减轻四氯化碳致小鼠急性肝损伤 被引量:1

Improvement of PUERARIAE LOBATAE RADIX-SCHISANDRAE SPHENANTHERAE FRUCTUS on Acute Liver Injury of Mice Induced by Carbon Tetrachloride with Prophylactic Administration
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摘要 目的:研究葛根-南五味子对四氯化碳(CCl4)诱导的急性肝损伤的保护作用,并初步探究其作用机制。方法:48只c57BL/6雄性小鼠随机分为正常对照组、模型对照组、水飞蓟素0.2 g/kg组、葛根-南五味子2.5、5、10 g/kg组,每组8只,连续给药14 d。末次给药后,除正常对照组外,每只小鼠按10 mL/kg腹腔注射2%CCl4橄榄油溶液,禁食16 h后收集小鼠血清和肝脏。生化法检测血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆固醇(TC)、三酰甘油(TG)、超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)和还原性谷胱甘肽(GSH)的活力或含量;ELISA法检测血清肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、IL-1β和IL-10的含量;TUNEL法检测小鼠肝组织细胞凋亡率;免疫荧光检测F4/80阳性率情况;免疫组化法检测肝组织中细胞色素P4502E1(CYP2E1)、中性粒细胞表面抗原(Ly6G)、BCL2-Associated X(BAX)、B淋巴细胞瘤-2基因(BCL-2)和半胱氨酸蛋白酶-3(Caspase-3)的蛋白表达。结果:与正常对照组比较,模型对照组出现肝细胞气球样变、脂变和坏死以及炎性浸润;血清中ALT、AST、TC、TG、TNF-α、IL-6和IL-1β活力或含量显著升高,且IL-10含量显著降低(P<0.01);肝组织中SOD活力、CAT和GSH含量显著降低,且MDA含量显著升高(P<0.01);肝组织中细胞凋亡率和F4/80阳性率显著增加(P<0.01);肝组织中CYP2E1、Ly6G、BAX、Caspase-3蛋白阳性表达显著增加,且BCL-2蛋白阳性表达显著降低(P<0.01);与模型对照组比较,葛根-南五味子各组呈剂量依赖性地缓解肝细胞气球样变、脂变和坏死减少以及炎症浸润,降低血清中ALT、AST、TC、TG、TNF-α、IL-6和IL-1β活力或含量,增加IL-10含量,增加肝组织中SOD、CAT和GSH活力或含量,降低MDA含量;减少肝组织中细胞凋亡率和F4/80阳性率,降低肝组织中CYP2E1、Ly6G、BAX、Caspase-3蛋白阳性表达,升高BCL-2蛋白阳性表达。结论:葛根-南五味子预防给药对CCl4所� Objective:To investigate the protective effect of PUERARIAE LOBATAE RADIX-SCHISANDRAE SPHENANTHERAE FRUCTUS on the acute liver injury of mice induced by carbon tetrachloride(CCl_4)and study its mechanism.Methods:48 c57BL/6 male mice were randomly divided into six groups:control group,model group,silymarin group(0.2 g/kg),PUERARIAE LOBATAE RADIX-SCHISANDRAE SPHENANTHERAE FRUCTUS pair groups(10,5,and 2.5 g/kg),with eight mice in each group,and these mice were administered continuously for 14 d.After the last dose,except for the control group,each mouse was injected intraperitoneally with CCl_4 olive oil solution of 10 mL/kg.After fasting for 16 h,serum and liver tissue were collected.The biochemical method was used to determine the activities or contents of serum alanine aminotransferase(ALT),aspertate aminotransferase(AST),total cholesterol(TC),triglyceride(TG),superoxide dismutase(SOD),malondialdehyde(MDA),catalase(CAT),and glutathione(GSH).Enzyme-linked immunosorbent assay(ELISA)was used to detect the contents of serum tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-1β(IL-1β),and interleukin-10(IL-10).TUNEL method was used to detect apoptosis rate in mice liver tissues.Immunofluorescence was used to detect the positive rate of F4/80.Immunohistochemistry was used to detect the expressions of cytochrome P4502E1(CYP2E1),neutrophil surface antigen(Ly6G),BCL2-associated X protein(Bax),B-cell lymphoma-2 gene(Bcl-2),and cysteine aspartate-specific protease-3(Caspase-3)in liver tissues.Results:Compared with those in the control group,the hepatocyte showed ballooning,lipid degeneration,and necrosis,and inflammatory infiltration in the model group,the activities and contents of ALT,AST,TC,TG,TNF-α,IL-6,and IL-1βwere significantly increased in serum,while IL-10 content was significantly reduced(P<0.01).The contents of SOD,CAT,and GSH in liver tissues were significantly reduced,and MDA content was significantly increased(P<0.01).In liver tissue,the apoptosis rate and F4/80 positivity rate were significa
作者 郭伟 胡田颖 雷宏强 詹博 李欢 翟秉涛 郭东艳 GUO Wei;HU Tianying;LEI Hongqiang;ZHAN Bo;LI Huan;ZHAI Bingtao;GUO Dongyan(Weinan Central Hospital,Weinan 714000;State Key Laboratory of Research&Development of Characteristic Qin Medicine Resources(Cultivation),and Shaanxi Province Key Laboratory of New Drugs and Chinese Medicine Foundation Research,Shaanxi University of Chinese Medicine,Xianyang 712046)
出处 《中药药理与临床》 CAS CSCD 北大核心 2023年第11期39-45,共7页 Pharmacology and Clinics of Chinese Materia Medica
基金 陕西中医药大学学科创新团队项目(编号:2019-YL11)。
关键词 葛根-南五味子 急性肝损伤 氧化应激 炎症 细胞凋亡 保肝作用 PUERARIAE LOBATAE RADIX-SCHISANDRAE SPHENANTHERAE FRUCTUS Acute liver injury Oxidative stress Inflammation Apoptosis Hepatoprotective effect
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