富马酸替诺福韦二吡呋酯联合聚乙二醇化干扰素对肝硬化大鼠肝细胞凋亡、免疫功能及内毒素水平的影响  

Effects of tenofovir dipyoproxil fumarate combined with pegylated interferon on hepatocyte apoptosis,immune function and endotoxin levels in cirrhotic rats*

作　　者：闪海霞[1] 卢瑞杰[1] 颜成果 王英[1] 和青森 范崇桂[1] Shan Haixia;Lu Ruijie;Yan Chengguo;Wang Ying;He Qingsen;Fan Chonggui(Infectious Diseases Department,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》2022年第6期521-525,541,F0003,共7页Chinese Journal of Anatomy

基　　金：河南省卫健委医学科技公关计划联合共建项目(LHGJ20200905)。

摘　　要：目的:研究富马酸替诺福韦二吡呋酯(TDF)联合聚乙二醇化α干扰素-2b(PEG-IFNα-2b)对肝硬化(代偿期)大鼠肝细胞凋亡、免疫功能及内毒素水平的影响。方法:大鼠随机分为对照组(健康大鼠常规饲养)、模型组(肝硬化模型组)、TDF治疗组(肝硬化模型+TDF)、干扰素治疗组(肝硬化模型+PEG-IFNα-1b)、联合治疗组(肝硬化模型+TDF+PEG-IFNα-2b)。H-E染色观察肠、肝病理形态。脱氧核苷酸末端转移酶介导缺口末端标记法测细胞凋亡指数(AI)。流式细胞术测免疫功能。鲨试剂显色基质法测内毒素。免疫组织化学检测大鼠肝组织Bax、Bcl-2蛋白表达。结果:模型组大鼠肝小叶结构破坏,肝细胞排列紊乱,可见片状坏死灶,有明显炎性细胞浸润。与模型组肝组织病变相比,TDF治疗组、干扰素治疗组与联合治疗组肝组织结构较为完整,肝细胞坏死减少,汇管区炎性细胞浸润也较模型组减轻,且以联合治疗组效果较为显著。模型组大鼠回肠黏膜上皮细胞变性、坏死,大量绒毛脱落,上皮下囊状间隙扩大,中央乳糜管扩张,固有层裸露,并伴有毛细血管扩张、充血;与模型组相比,TDF治疗组、干扰素治疗组、联合治疗组均有所改善,且以联合治疗组效果明显。与对照组相比,模型组大鼠内毒素、肝细胞凋亡、CD8^(+)T淋巴细胞数、Bax升高,Bcl-2、CD3^(+)T淋巴细胞数、CD4^(+)T淋巴细胞数、CD4^(+)/CD8^(+)降低。与联合治疗组相比,TDF治疗组与干扰素治疗组内毒素、肝细胞凋亡、CD8^(+)T淋巴细胞数、Bax降低,Bcl-2、CD3^(+)T淋巴细胞数、CD4^(+)T淋巴细胞数、CD4^(+)/CD8^(+)升高。与干扰素治疗组相比,联合治疗组内毒素、肝细胞凋亡、CD8^(+)T淋巴细胞数、Bax降低,Bcl-2、CD3^(+)T淋巴细胞数、CD4^(+)T淋巴细胞数、CD4^(+)/CD8^(+)升高。结论:TDF联合IFNα-1b通过提高肝硬化(代偿期)大鼠免疫功能,降低内毒素水平以及减少肝细胞凋亡,改善肝硬Objective:To study the effects of tenofovir disoproxil fumarate(TDF)combined with pegylated IFNα-2b(PEG-IFNα-2b)on liver cell apoptosis,immune function,and endotoxin levels in cirrhotic rats.Methods:Rats were randomly divided into a control group(normal feeding),a model group(liver cirrhosis model group),a TDF treatment group(liver cirrhosis model+TDF),a interferon treatment group(liver cirrhosis model+PEGIFNα-1b),and a combination treatment group(liver cirrhosis model+TDF+PEG-IFNα-2b).H-E staining was used to observe the morphology of intestinal and liver diseases.Apoptosis was measured by deoxynucleotide terminal transferase mediated Nick end labeling.Immune function was measured by flow cytometry.Detection of endotoxin by shark reagent chromogenic matrix.Bax and Bcl-2 were detected by immunohistochemistry.Results:In the model group,the hepatic lobule structure of rats was damaged,the arrangement of hepatocytes was disordered,there were patellar necrosis foci and obvious inflammatory cell infiltration.Compared with the model group,the liver tissue structure of the TDF treatment group,interferon treatment group and combination treatment group was more complete,the necrosis of hepatocytes was reduced,and the infiltration of inflammatory cells in the portal area was also reduced,and the effect of the combination treatment group was more significant.In the model group,the ileum mucosal epithelial cells were denaturated and necrotic,a large number of villi were shed,the subepithelial cystic space was expanded,the central chylus duct was dilated,the lamina propria was exposed,accompanied by telangiectasia and congestion.Compared with the model group,the TDF treatment group,interferon treatment group and combination treatment group were improved,and the combination treatment group had a significant effect.Compared with the control group,the levels of endotoxin,hepatocyte apoptosis,CD8^(+)T lymphocyte and Bax were increased in the model group,while the levels of Bcl-2,CD3^(+)T lymphocyte,CD4^(+)T lymphocyte and CD4

关 键 词：富马酸替诺福韦二吡呋酯 聚乙二醇化干扰素 肝硬化 肝细胞 免疫功能 内毒素 

分 类 号：R575.2[医药卫生—消化系统]