DPP4-Nestin轴在泡球蚴感染所致肝纤维化的促进作用及机制  

Role and mechanism of DPP4-nestin axis in liver fibrosis induced by Echinococcus alveolar infection

作　　者：高瑾 孙涛 木克西娜·木拉提 何小龙 石晶 李亮 杨宁 楚瑨 张雪 刘辉 吕国栋 林仁勇 毕晓娟 郭庆勇[1] GAO Jin;SUN Tao;MUKEXINA Mulati;HE Xiaolong;SHI Jing;LI Liang;YANG Ning;CHU Jin;ZHANG Xue;LIU Hui;LYU Guodong;LIN Renyong;BI Xiaojuan;GUO Qingyong(Xinjiang Key Laboratory of New Drug Study and Creation for Herbivorous Animals,College of Veterinary Medicine,Xinjiang Agricultural University,Urumqi 830052,China;State Key Laboratory of Pathogenesis Prevention and Treatment of High Incidence Diseases in Central Asia,Clinical Medical Research Institute,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China;Basic Medical College of Xinjiang Medical University,Urumqi 830054,China;College of Life Science and Technology,Xinjiang University,Urumqi830046,China)

机构地区：[1]新疆农业大学动物医学学院新疆草食动物新药研究与创制重点实验室,新疆乌鲁木齐830052 [2]新疆医科大学第一附属医院临床医学研究院省部共建中亚高发病成因与防治国家重点实验室,新疆乌鲁木齐830054 [3]新疆医科大学基础医学院,新疆乌鲁木齐830054 [4]新疆大学生命科学与技术学院,新疆乌鲁木齐830046

出　　处：《中国兽医学报》2025年第2期298-304,共7页Chinese Journal of Veterinary Science

基　　金：国家自然科学基金资助项目(82060371,32060223);新疆维吾尔自治区自然科学基金资助项目(2022D01D59);新疆维吾尔自治区自然科学基金资助项目(2022D01C255,2022D01C762);新疆维吾尔自治区“天山英才”培养计划资助项目(2022TSYCLJ0032);杰出青年科学基金资助项目(2022D01E67);省部共建中亚高发病成因与防治国家重点实验室开放课题包虫专项资助项目(SKL-HIDCA-2022-BC2)。

摘　　要：为探讨DPP4-Nestin轴在泡球蚴感染引起肝纤维化过程中的作用,选取C57BL/6小鼠通过肝门静脉构建泡球蚴感染模型,HE法检测肝脏组织病理学变化,免疫组化、免疫荧光检测Nestin及DPP4在泡球蚴感染小鼠肝脏中的表达;以DPP4重组蛋白刺激小鼠肝星状细胞系JS1构建体外模型,qPCR、Western blot、shRNA慢病毒干扰等方法检测DPP4-Nestin轴在肝星状细胞激活过程中的作用。结果显示:与Sham组相比,泡球蚴感染组肝脏组织结构破坏,胶原沉积明显,Nestin和DPP4表达显著升高(P<0.050 0),且Nesin与α-SMA存在共定位;与对照组相比,DPP4重组蛋白刺激可明显刺激JS1细胞激活(P<0.050 0),并且Nestin表达升高(P<0.050 0),shRNA慢病毒抑制JS1细胞Nestin表达可明显抑制DPP4重组蛋白对JS1细胞的活化作用(P<0.050 0)。综上所述,DPP4-Nestin轴在泡球蚴感染引起肝星状细胞活化过程中具有重要调节作用,靶向DPP4-Nestin轴可作为治疗泡球蚴感染所致肝纤维化的新途径。To investigate the role of the DPP4-nestin axis in liver fibrosis induced by alveolar cyst infection,a murine model was established using C57BL/6 mice via hepatic portal vein injection.Liver histopathological changes were assessed using HE staining,while immunohistochemistry and immunofluorescence were employed to evaluate the expression levels of nestin and DPP4 in infected mouse livers.In vitro,JSl cell line was stimulated with recombinant DPP4 protein to establish a cellular model,and qPCR,Western blot,and shRNA lentivirus interference techniques were utilized to examine the involvement of the DPP4-nestin axis in hepatic stellate cell activation.The findings demonstrated that compared to the Sham group,liver tissue structure disruption and collagen deposition were evident along with significantly increased expressions of nestin and DPP4(P<0.0500),which colocalized with nesin andα-SMA.Furthermore,stimulation with recombinant DPP4 protein significantly enhanced JS1 cell activation(P<0.0500)as well as upregulated nestin expression(P<0.0500)when compared to control group cells.Notably,shRNA lentivirusmediated inhibition of nestin expression effectively suppressed the activating effects exerted by recombinant DPP4 protein on JS1 cells(P<0.0500).Collectively,these results highlight the crucial regulatory role played by the DPP4-nestin axis in hepatic stellate cell activation triggered by alveolar infection;thus,targeting this axis may represent a novel therapeutic strategy for treating alveolar infection-induced liver fibrosis.

关 键 词：泡型棘球蚴 NESTIN DPP4 小鼠 

分 类 号：S855.9[农业科学—临床兽医学]