基于JAK/STAT通路EFhD2蛋白对肺癌大鼠T淋巴细胞免疫功能的调节作用研究  

Regulatory effect of EFhD2 protein based on JAK/STAT pathway on T lymphocyte immune function of lung cancer rats

作　　者：翟占强 江立群[2] 朱佳[2] 张典钿[2] 汤灵玲 ZHAI Zhan-Qiang;JIANG Li-Qun;ZHU Jia;ZHANG Dian-Dian;TANG Ling-Ling(Chest Disease Diagnosis and Treatment Center of Zhejiang Rongjun Hospital,Jiaxing 314000,China)

机构地区：[1]浙江省荣军医院胸部疾病诊疗中心,嘉兴314000 [2]江苏省靖江市人民医院胸外科,泰州214500 [3]树兰(杭州)医院感染科,杭州310000

出　　处：《中国免疫学杂志》2021年第14期1672-1676,1681,共6页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(2017ZX10204401)。

摘　　要：目的:探讨螺旋-环-螺旋拓扑结构域蛋白D2(EFhD2)基于Janus激酶/信号转导与转录激活子(JAK/STAT通路对肺癌大鼠T淋巴细胞免疫功能的调节作用。方法:气管内灌注致癌碘油液法建立肺癌大鼠模型,分为模型组(生理盐水)、sh-EFhD2组(shRNA-EFhD2重组腺病毒载体^(+)生理盐水)、EFhD2组(mimic-EFhD2重组腺病毒载体+生理盐水)、EFhD2-AG490组(mimic-EFhD2重组腺病毒载体^(+)JAK2抑制剂AG490),同法灌注碘油为对照组(生理盐水),均尾静脉注射,1次/周,共8周。检测各组外周血CD3^(+)、CD4^(+)、CD8^(+)占比及CD4^(+)/CD8^(+),计算肺指数、脾脏指数,观察肺组织病理形态,检测肺组织中EFhD2、JAK2、磷酸化JAK2(p-JAK2)、STAT3、p-STAT3蛋白表达量。结果:病理组织学显示,模型组、sh-EFhD2组、EFhD2组、EFhD2-AG490组分别有13、10、15、11只诱发肺癌。与对照组相比,模型组、sh-EFhD2组、EFhD2组及EFhD2-AG490组外周血CD3^(+)、CD4^(+)占比、CD4^(+)/CD8^(+)及脾脏指数均降低,其中CD3^(+)、CD4^(+)占比:EFhD2组模型组和EFhD2-AG490组>sh-EFhD2组(P<0.05)。与对照组相比,模型组、sh-EFhD2组、EFhD2组及EFhD2-AG490组EFhD2、p-JAK2、p-STAT3蛋白相对表达量均升高,且EFhD2组>EFhD2-AG490组>模型组>sh-EFhD2组(P<0.05)。结论:抑制EFhd2蛋白表达可增强肺癌大鼠T淋巴细胞免疫功能,可能通过抑制JAK2、STAT3蛋白磷酸化发挥调控作用。Objective:To investigate the regulatory effect of helix-loop-helix topology protein D2(EFhD2)based on the Janus kinase/signal transduction and transcription activator(JAK/STAT)pathway on the T lymphocyte immune function of lung cancer rats.Methods:Establishment of rat model of lung cancer by intratracheal infusion of carcinogenic iodine oil,which was divided into model group(normal saline),sh-EFhD2 group(shRNA-EFhD2 recombinant adenovirus vector+normal saline),and EFhD2 group(mimicEFhD2 recombinant adenovirus vector+normal saline),EFhD2-AG490 group(mimic-EFhD2 recombinant adenovirus vector+JAK2 inhibitor AG490),and iodine oil infusion with the same method is set as control group(normal saline),which were injected by tail vein once a week for 8 weeks.Proportion of CD3^(+),CD4^(+),CD8^(+)and CD4^(+)/CD8^(+)in peripheral blood were detected after intervention.Lung index and spleen index were calculated,pathological morphology of lung tissue was observed,and expressions of EFhD2,JAK2,pJAK2,STAT3 and p-STAT3 were measured.Results:Histopathology showed that 13,10,15,and 11 cases induced lung cancer in model group,sh-EFhD2 group,EFhD2 group and EFhD2-AG490 group,respectively.Compared with control group,proportion of CD3^(+),CD4^(+),CD8^(+)and CD4^(+)/CD8^(+)in peripheral blood and spleen index of model group,sh-EFhD2 group,EFhD2 group and EFhD2-AG490 group were all reduced,among them,proportion of CD3^(+),CD4^(+):EFhD2 group<EFhD2-AG490 group<model group<sh-EFhD2 group,CD4^(+)/CD8^(+)and spleen index:EFhD2 group<model group and EFhD2-AG490 group<sh-EFhD2 group(P<0.05).Compared with control group,peripheral blood CD8^(+)ratio and lung index of model group,sh-EFhD2 group,EFhD2 group and EFhD2-AG490 group were increased,and EFhD2 group>model group and EFhD2-AG490 group>sh-EFhD2 group(P<0.05).Compared with control group,relative expressions of EFhD2,p-JAK2,and p-STAT3 protein in model group,sh-EFhD2 group,EFhD2 group and EFhD2-AG490 group all increased,and EFhD2 group>EFhD2-AG490 group>model group>sh-EFhD2 group(P<0.05).Con

关 键 词：肺癌 T淋巴细胞免疫功能 螺旋-环-螺旋拓扑结构域蛋白D2 基于Janus激酶 信号转导与转录激活子 大鼠 

分 类 号：R332[医药卫生—人体生理学]