桑黄酸性多糖对胆管结扎所致小鼠肝纤维化的改善作用及其机制  

Improvement effect of Phellinus igniarius acidic polysaccharide on liver fibrosis induced by bile duct ligation in mice and its mechanism

作　　者：谷明柳 林逢源 吴雪峰 周嘉宁 卢学春[2] 杜培革 安丽萍 GU Mingliu;LIN Fengyuan;WU Xuefeng;ZHOU Jianing;LU Xuechun;DU Peige;AN Liping(Department of Microbiology and Biochemical Pharmacy,School of Pharmacy,Beihua University,Jilin 132013,China;Department of Hematology,Second Medical Center&National Clinical Research Center for Geriatric Diseases,Chinese PLA General Hospital,Beijing 100853,China)

机构地区：[1]北华大学药学院微生物与生化药学教研室,吉林吉林132013 [2]解放军总医院第二医学中心血液科国家老年疾病临床研究中心,北京100853

出　　处：《吉林大学学报（医学版）》2022年第5期1167-1174,共8页Journal of Jilin University：Medicine Edition

基　　金：吉林省发改委产业创新专项资金项目(2018C046-3)。

摘　　要：目的:探讨桑黄酸性多糖(PIP)对胆管结扎(BDL)所致小鼠肝纤维化的改善作用,阐明其可能的作用机制。方法:60只4周龄雄性C57/BL6小鼠随机分为对照组、模型组、阳性药组和PIP给药组(PIP组),每组15只。对照组小鼠只绕胆总管穿过手术线但不结扎,模型组、阳性药组和PIP组小鼠结扎胆管。术后给药3周,末次给药12 h后眼球取血,处死小鼠。称量小鼠体质量和肝脏质量,并计算肝脏指数;微板法检测各组小鼠血清中丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)水平;双抗体夹心法检测各组小鼠血清中Ⅲ型前胶原(PCⅢ)和Ⅳ型胶原(ColⅣ)水平;HE染色和天狼猩红染色观察各组小鼠肝组织病理形态表现和肝纤维化程度;检测各组小鼠肝组织中超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性及丙二醛(MDA)和谷胱甘肽(GSH)水平。Western blotting法检测各组小鼠肝组织中核因子E2相关因子(Nrf2)、血红素加氧酶1(HO-1)和醌氧化还原酶1(NQO1)蛋白表达水平。结果:与对照组比较,模型组小鼠体质量差异无统计学意义(P>0.05),肝脏质量和肝脏指数均升高(P<0.05);与模型组比较,PIP组小鼠体质量无明显变化(P>0.05),肝脏质量和肝脏指数降低(P<0.05)。HE染色,对照组小鼠肝组织无异常表现;模型组小鼠肝组织中肝小叶结构破坏,可见灶状液化性肝坏死和较多炎症细胞浸润;与模型组比较,阳性药组和PIP组小鼠肝组织坏死程度明显减轻,炎症细胞浸润减少。天狼猩红染色,与对照组比较,模型组小鼠肝组织中胶原纤维含量明显增加;与模型组比较,PIP组小鼠肝组织胶原纤维含量明显减少。与对照组比较,模型组小鼠血清中ALT和AST水平明显升高(P<0.01),PCⅢ和ColⅣ水平明显升高(P<0.05),小鼠肝组织中SOD和GSH-Px活性明显降低(P<0.01),MDA和GSH水平明显升高(P<0.05或P<0.01);与模型组比较,阳性药组和PIP组小鼠血清中ALT和AST�Objective:To investigate the improvement effect of Phellinus igniarius acidic polysaccharide(PIP)on liver fibrosis in the mice induced by bile duct ligation(BDL),and to clarify its possible mechanism.Methods:A total of sixty 4-week-old male C57/BL6 mice were randomly divided into control group,model group,positive drug group,and PIP group,with 15 mice in each group.The mice in control group only received the passed surgical line without ligation around the common bile duct,and the bile duct of mice in model group,postive drug group and PIP group were ligated.After administration for 3 weeks,the blood was taken from eyeball 12 h after the last administration,and the mice were sacrificed.The body weights and liver weights of mice were weighed,and the liver index was calculated.Microplate method was used to determine the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum of the mice in various goups;the levels of typeⅢprocollagen(PCⅢ)and cellagen typeⅣ(ColⅣ)in serum were determined by double antibody sandwich method.HE staining and Sirius red staining were used to observe the pathomorphology and fibrosis degrees of liver tissue of the mice in various groups;the activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)and the levels of malondialdehyde(MDA)and glutathione(GSH)in liver tissue of the mice in various groups were determined.The expression levels of nuclear factor-E2 related factor(Nrf2),heme oxygenase-1(HO-1)and quinone oxidoreductase 1(NQO1)proteins in liver tissue of the mice in various groups were detected by Western blotting method.Results:Compared with control group,the body weight of the mice in model group had no significant difference(P>0.05),and the liver weight and liver index were increased(P<0.05);compared with model group,the body weight of the mice in PIP group had no significant change(P>0.05),and the liver weight and liver index were decreased(P<0.05).The HE staining results showed no abnormalities in liver tissue of the mice in contr

关 键 词：桑黄酸性多糖 肝纤维化 胆管结扎 核因子E2相关因子 血红素加氧酶1 

分 类 号：R575.2[医药卫生—消化系统]