核苷(酸)类似物联合聚乙二醇干扰素对慢性乙型肝炎大鼠法尼醇X受体-成纤维细胞生长因子19通路、枯否细胞极化的影响  

Effects of nucleoside acid analogues combined with pegylated interferon on farnesol X receptor-fibroblast growth factor 19 pathway and Kupffer cell polarization in chronic hepatitis B rats

作　　者：颜成果 闪海霞[1] 吴玉卓[1] 卢瑞杰[1] 温泉 Yan Chengguo;Shan Haixia;Wu Yuzhuo;Lu Ruijie;Wen Quan(Department of Infectious Diseases,Nanyang Central Hospital,Nanyang 473000,China)

机构地区：[1]南阳市中心医院感染性疾病科,南阳473000

出　　处：《解剖学杂志》2023年第5期390-394,共5页Chinese Journal of Anatomy

基　　金：河南省医学科技公关计划联合共建项目(LGHJ20191457)。

摘　　要：目的 :探究核苷(酸)类似物联合聚乙二醇干扰素对慢性乙型肝炎大鼠法尼醇X受体(FXR)-成纤维细胞生长因子19(FGF19)通路、枯否细胞极化的影响。方法 :选取SPF级SD雄性大鼠,随机分为正常组、模型组、核苷(酸)类似物(核苷酸)组、聚乙二醇干扰素(干扰素)组、联合组。除正常组外,均采用腹腔注射乙型肝炎病毒进行慢性乙型肝炎建模。建模成功后,对核苷酸组灌胃10 mg/kg拉米夫定,对干扰素组皮下注射5μg/kg聚乙二醇干扰素,对联合组给予拉米夫定联合聚乙二醇干扰素治疗,正常组、模型组同期灌胃同体积生理盐水。酶联免疫吸附法检测血清病毒,全自动生化分析仪检测肝功能,H-E染色法检测肝组织病理形态,免疫印迹法检测FXRFGF19通路蛋白表达,免疫组织化学法检测枯否细胞极化。结果 :与正常组相比,模型组血清乙型肝炎表面抗原(HBsAg)、乙型肝炎E抗原(HBeAg)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)含量、iNOS、CD163阳性表达率显著升高,肝组织FXR、FGF19蛋白表达显著降低。与模型组相比,核苷酸组、干扰素组、联合组血清HBsAg、HBeAg、ALT、AST、TBIL含量、iNOS、CD163阳性表达率显著降低。肝组织FXR、FGF19蛋白表达显著升高,联合组比干扰素组降低显著。结论 :核苷(酸)类似物联合聚乙二醇干扰素,可显著激活FXR-FGF19通路,并抑制枯否细胞M1极化,促进枯否细胞M2极化,对慢性乙型肝炎大鼠具有改善作用。Objective:To investigate the effects of nucleoside(acid)analogues combined with pegylated interferon on farnesol X receptor(FXR)-fibroblast growth factor 19(FGF19)pathway and Kupffer cell polarization in chronic hepatitis B rats.Methods:SPF SD male rats were randomly divided into normal group,model group,nucleoside(acid)analogue(nucleotide)group,pegylated interferon(interferon)group,and combination group.Except for the normal group,chronic hepatitis B was modeled by intraperitoneal injection of hepatitis B virus.After successful modeling,the nucleotide group was given 10 mg/kg lamivudine.The interferon group was subcutaneously injected with 5μg/kg pegylated interferon,and the combined group was given lamivudine combined with pegylated interferon.The normal group and the model group were given gavage with the same volume of normal saline at the same time.Serum virus was detected by enzyme-linked immunosorbent assay,liver function was detected by automatic biochemical analyzer,and pathological morphology of liver tissue was detected by H-E staining.The expression of FXR-FGF19 pathway protein was detected by Western blotting and Kuper cell polarization was detected by immunohistochemistry.Results:Compared with the normal group,the serum HBsAg,HBeAg,ALT,AST,TBIL,iNOS and CD163 positive expression rates were significantly increased in the model group,while the protein expressions of FXR and FGF19 in liver tissue were significantly decreased.Serum HBsAg,HBeAg,ALT,AST,TBIL,iNOS and CD163 positive expression rates were significantly decreased in nucleotide group,interferon group and combination group,while FXR and FGF19 protein expressions in liver tissue were significantly increased,and the combination group showed significant reducition compared with the interferon group.Conclusion:Nucleoside(acid)analogues combined with pegylated interferon can significantly activate FXR-FGF19 pathway,inhibit Kupffer cell M1 polarization,and promote Kupffer cell M2 polarization,and have an improvement effect on rats with chronic hepa

关 键 词：核苷(酸)类似物 聚乙二醇干扰素 慢性乙型肝炎 法尼醇X受体-成纤维细胞生长因子19通路 枯否细胞 大鼠 

分 类 号：R512.62[医药卫生—内科学]