枸杞多糖对α-萘基异硫氰酸酯诱导的大鼠胆汁淤积性肝损伤及TLR4/MyD88/NF-κB通路相关蛋白表达的影响  

Effects of Lycium barbarum polysaccharides on ANIT-induced cholestatic liver injury and the expression of TLR4/MyD88/NF-κB pathway-related proteins in rats

作　　者：夏勇[1] 董晓岚[2] 陈钢[1] 蔡德雷[1] XIA Yong;DONG Xiaolan;CHEN Gang;CAI Delei(Zhejiang Provincial Center for Disease Control and Prevention,Hangzhou,Zhejiang 310051,China;Zhejiang Provincial Hospital of Traditional Chinese Medicine,Hangzhou,Zhejiang 310009,China)

机构地区：[1]浙江省疾病预防控制中心,浙江杭州310051 [2]浙江省中医院,浙江杭州310009

出　　处：《实用预防医学》2024年第12期1432-1438,共7页Practical Preventive Medicine

基　　金：浙江省中医药科学研究基金项目(2022ZB091);浙江卫生健康科技计划项目(2022PY045)

摘　　要：目的 观察枸杞多糖(Lycium barbarum polysaccharides, LBP)对α-萘基异硫氰酸酯诱导的大鼠胆汁淤积性肝损伤及Toll样受体4(Toll-like receptor 4,TLR4)/髓样细胞分化因子88(myeloid differentiation factor 88,MyD88)/核因子kappa B(nuclear factor kappa-B,NF-κB)通路相关蛋白表达的影响。方法 设正常对照组、模型组和LBP低、中、高剂量组及阳性对照组,连续灌胃给受试物6周后,采集血液及肝脏组织样本,测定大鼠血清标志物指标、血液白细胞总数及分类指标,肝组织中炎症因子含量以及TLR4、NF-κB、磷酸化核因子kappa B(phospho-nuclear factor kappa B,pNF-κB)、MyD88的相对表达水平,采用HE和masson染色,观察大鼠肝脏组织形态并进行组织病理学评分。结果 与正常对照组比较,模型组大鼠血清γ-谷氨酰转移酶(γ-glutamyltransferase, γ-GGT)、碱性磷酸酶(alkaline phosphatase, ALP)、总胆汁酸(total bile acid, TBA)、总胆红素(total bilirubin, TBIL)、胆固醇(cholesterol, CHOL)、谷丙转氨酶(alanine aminotransferase, ALT)、谷草转氨酶(aspertate aminotransferase,AST)和血液白细胞总数(white blood cells,WBC)、淋巴细胞数(lymphocyte,LYMPH)、中性粒细胞数(neutrophil,NEUT)、单核细胞数(monocyte,MONO)均升高(P<0.01),肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素-1(interleukin-1,IL-1)、白细胞介素-6(interleukin-6,IL-6)及大鼠单核细胞趋化因子1(monocytechemotactic 1,CCL2)、巨噬细胞炎症蛋白2(macrophage inflammatory protein 2,CXCL2)含量增加,TLR4、pNF-κB、MyD88表达水平上调(P<0.01),肝重和肝/体比增加,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(P<0.01);与模型组比较,LBP高剂量组大鼠血清γ-GGT、TBA、TBIL、ALT水平和血液WBC、LYMPH、NEUT计数值下降(P<0.05或P<0.01),肝组织中炎症因子TNF-α、IL-1、IL-6及CXCL2含量降低,TLR4、pNF-κB、MyD88蛋白相对表达水平下Objective To observe the effects of Lycium barbarum polysaccharides(LBP)onα-naphthyl isothiocyanate induced cholestatic liver injury and the expression of Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor kappa-B(TLR4/MyD88/NF-κB)pathway-related proteins.Methods The normal control group,the model group,the LBP low-,middle-and high-dose groups and the positive control group were established.After 6 weeks of continuous intragastric administration of test substances,rats’blood and liver tissue samples were collected to detect serum biomarker indicators,total white blood cell(WBC)count and classification indicators,inflammatory factor content in liver tissue,and relative expression levels of TLR4,NF-κB,phospho-nuclear factor kappa B(pNF-κB)and MyD88 proteins.HE staining and Masson staining methods were used to observe the morphological changes in the liver tissue of rats,and histopathological scoring was performed.Results Compared with the normal control group,the serum levels ofγ-glutamyltransferase(γ-GGT),alkaline phosphatas(ALP),total bile acid(TBA),total bilirubin(TBIL),cholesterol(CHOL),alanine aminotransferase(ALT)and aspertate aminotransferase(AST)as well as total WBC count,lymphocyte(LYMPH),neutrophil(NEUT)and monocyte(MONO)in the model group increased(all P<0.01),the levels of tumor necrosis factor-α(TNF-α),interleukin-1(IL-1),interleukin-6(IL-6),monocyte chemotactic protein-1(CCL2)and macrophage inflammatory protein-2(CXCL2)increased,the expression levels of TLR4,pNF-κB and MyD88 were upregulated(P<0.01),liver weight and liver to body weight ratio increased,pathological changes in the liver such as infiltration of inflammatory cells,bile duct hyperplasia and fibrous tissue hyperplasia were observed,and the histological observation score increased(P<0.01).Compared with the model group,the serumγ-GGT,TBA,TBIL and ALT levels,WBC count,LYMPH and NEUT in the LBP high-dose group decreased(P<0.05 or P<0.01),the levels of TNF-α,IL-1,IL-6 and CXCL2 in the liver tissue decreased,the r

关 键 词：枸杞多糖 胆汁淤积性肝损伤 Toll样受体4/髓样细胞分化因子88/核因子kappa B通路相关蛋白 

分 类 号：R575[医药卫生—消化系统]