枸杞多糖对肝内胆汁淤积模型大鼠肝脏预防保护作用的研究  

Study on the relieving and protective effects of lycium barbarum polysaccharides on the liver of rats model with intrahepatic cholestasis model

作　　者：夏勇[1] 宋燕华[1] 曹彬 陈钢[1] XIA Yong;SONG Yanhua;CAO Bin;CHEN Gang(Zhejiang Provincial Center for Disase Control and Preven-tion,Hangzhou 310051,Zheyjiang China)

机构地区：[1]浙江省疾病预防控制中心,杭州310051

出　　处：《现代实用医学》2024年第5期570-575,共6页Modern Practical Medicine

基　　金：浙江省中医药科技计划(2022ZB091)。

摘　　要：目的 探讨枸杞多糖(LBP)对肝内胆汁淤积模型大鼠肝脏损伤的预防保护作用。方法 SPF级雄性SD幼龄大鼠,设阴性对照组、模型组、LBP 50、150、450 mg/kg剂量组,以及阳性对照组,每组各10只。构建大鼠肝内胆汁淤积模型,模型组、LBP各剂量组及阳性对照组,予60mg/kg α-萘异硫氰酸酯,每隔1天给药一次,第2周开始改为每隔3天给药一次,持续6周。第2周起,各剂量组每天予不同剂量的LBP,阳性对照组予熊去氧胆酸,模型组大鼠予蒸馏水。6周后采集血液及肝组织样本,测定血清生化指标、凝血功能指标及白细胞分类计数指标,检测肝组织中的炎症因子含量以及Toll样受体4(TLR4)、核因子κB(NF-κB)、核转录因子(pNF-κB)及髓分化因子88(MyD88)蛋白的表达量,观察大鼠肝脏的病变情况。结果 与阴性对照比较,模型组大鼠血清γ-谷氨酰转移酶(γ-GGT)、碱性磷酸酶(ALP)、总胆汁酸(TBA)、总血红素(TBiL)、胆固醇(CHOL)、丙氨酸氨基转移酶(ALT)及天冬氨酸氨基转移酶(AST)水平,血液白细胞(WBC)、淋巴细胞(LYMP)、中性粒细胞(NEUT)、单核细胞(MONO)及嗜酸性粒细胞(EO)计数,纤维蛋白原(FIB)含量均升高(均P <0.05),肝组织中炎症因子肿瘤坏死因子(TNF-α)、白介素1β(IL-1β)、白介素6及巨噬细胞炎性蛋白2(MIP-2)含量增加,TLR4、pNF-κB、MyD88蛋白表达水平上调(均P <0.05)。肝脏可见多量炎症细胞浸润、胆管增生、纤维组织增生等病理性改变,组织形态学观察评分上升(均P <0.05);与模型组比较,LBP450mg/kg组大鼠血清γ-GGT、TBA、TBiL、ALT水平,血液WBC、LYMP、NEUT计数,FIB含量均下降(均P<0.05),肝组织中炎症因子TNF-α、IL-1β、MIP-2含量降低,TLR4、pNF-κB、MyD88蛋白的表达水平下调(均P<0.05),肝脏组织形态学观察评分下降(均P <0.05),肝脏损伤减轻,LBP 150 mg/kg组大鼠血液FIB含量均下降,TLR4蛋白的表达水平下调(均P<0.05)。结论 LBP对肝内胆汁淤积模�Objective To study the relieving and protective effects of lycium barbarum polysaccharides(LBP)on liver injury in rats model with intrahepatic cholestasis.Methods The model of intrahepatic cholestasis in SPF male sprague-dawley(SD)rats was established,and the negative control group,positive control group,model group,LBP dose groups of 50,150 and 450 mg/kg were set up.The model group,each dose group of LBP,and positive control group was given 60 mg/kg-Naphthalene isothiocyanate(ANIT)every other day,and from the second week,it was changed to every three days for a duration of six weeks.From the second week,different doses of LBP were given to each dose group,ursodeoxycholic acid was given to the positive control group,and distilled water was given to the model group.After six weeks,blood and liver tissue samples were collected to measure serum biochemical indicators,coagulation function indicators and white blood cell(WBC)classification count indicators.The content of inflamma-tory factors and the expression levels of TLR4,nuclear factor(NF)-B,pNF-B,and MyD88 proteins in rat liver tissue were measured,and the pathological changes in rat liver were observed.Results Compared to the negative control gro-up,the values of the serum-GGT,alkaline phosphatase(ALP),total bile acid(TBA),total bilirubin(TBiL),cholesterol(CHOL),ALT,AST levels,the blood WBC,lymphocyte(LYMP),neutrophile granulocyte(NEUT),mononuclear leuco-cyte(MONO),eosinophilic granulocyte(EO)counts,and fibrinogen(FIB)content increased in model group(all<0.05),and the concentration of TNF-,IL-1,IL-6 and macrophage inflammtory protein(MIP)-2 increased,and the levels of TLR4,pNF-B and MyD88 proteins were upregulated(all<0.05).Pathological changes such as excessive inflamma-tion,bile duct hyperplasia,and fibrous tissue hyperplasia were observed,and the observation score increased in model gro-up(all<0.05).Compared with the model group,the LBP 450 mg/kg group serum transglutaminase(-GGT),TBA,TBiL,ALT,blood WBC,LYMP,NEUT counts,and FIB concentration all decreased(al

关 键 词：枸杞多糖 胆汁淤积 保肝作用 TLR4/MyD88/NF-B信号通路 

分 类 号：R285.5[医药卫生—中药学]