维生素D3通过增强肝组织维生素D受体活性阻断JAK/STAT3通路减轻高胆固醇血症小鼠幽门螺杆菌感染相关胃炎  

Vitamin D3 alleviates the gastritis that associated with Helicobacter pylori infection in mice with hypercholesterolemia by enhancing the activity of vitamin D receptors in the liver tissue and blocking the signaling pathway of JAK/STAT3

作　　者：徐文娇 王丽萍 杨利娟 李向妮 李昌平 刘保民 XU Wenjiao;WANG Liping;YANG Lijuan;LI Xiangni;LI Changping;LIU Baomin(Ultrasound Diagnosis and Treatment Center,North Campus of Xi’an International Medical Center Hospital,Xi’an 710000;Department of Gastroenterology,Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西安国际医学中心医院北院区超声诊疗中心,陕西西安710000 [2]西南医科大学附属医院消化内科,四川泸州646000

出　　处：《细胞与分子免疫学杂志》2024年第6期520-526,共7页Chinese Journal of Cellular and Molecular Immunology

基　　金：四川省中医药管理局2017年度科技专项课题(2016Q071)。

摘　　要：目的 探讨维生素D3(VD3)能否通过降低血脂抑制Janus激酶/信号转导子与转录激活子3(JAK/STAT3)信号通路从而减轻幽门螺杆菌(Hp)感染。方法 建立高胆固醇小鼠模型和Hp感染小鼠模型,采用VD3灌胃8周。采用实时定量PCR检测小鼠肝组织维生素D受体(VDR)、胰岛素诱导基因2(Insig-2)及小鼠胃组织胃泌素的mRNA表达,Western blot法检测胃组织JAK、STAT3、环加氧酶2(COX2)蛋白的表达,生化分析法检测小鼠血清胆固醇水平,ELISA检测各组小鼠血清白细胞介素6(IL-6)及IL-8水平,HE染色小鼠肝组织及胃组织的病变情况。结果 高胆固醇组及高胆固醇联合Hp感染组小鼠在灌胃VD3后,小鼠肝组织VDR、Insig-2的水平明显上升,胃泌素水平表达降低;胃组织JAK、STAT3及COX2蛋白的表达降低,血清中胆固醇水平降低,IL-6水平无明显变化,IL-8水平降低;与对照组相比,高胆固醇联合Hp感染组肝细胞气球样变减少,胃组织炎症减轻,胆固醇组、Hp感染组胃组织炎症也减轻。结论 VD3通过增强肝组织VDR的活性,阻断JAK/STAT3信号通路,抑制炎症因子表达减轻胃炎的程度。Objective To investigate whether vitamin D3(VD3)can alleviate Helicobacter pylori(Hp)infection by reducing blood lipids and inhibiting the Janus kinase/signal transducer and activator of transcription 3(JAK/STAT3)signaling pathway.Methods High-cholesterol mouse model and Hp infected mouse model were established.Each was treated with VD3 via oral administration for 8 weeks.Real-time quantitative PCR was used to detect the expression of vitamin D receptor(VDR),insulin-induced gene 2(Insig-2),and gastrin mRNA.Western blot analysis was used to examine the expression of JAK,STAT3,and cyclooxygenase-2(COX2)proteins in gastric tissues.Biochemical analyses were performed to measure serum cholesterol levels,and ELISA was utilized to evaluate serum gastrin,interleukin 6(IL-6),and IL-8 levels,along with histopathological examination of liver and gastric tissues using HE staining.Results After oral administration of VD3,the levels of VDR and Insig-2 in mouse liver tissue significantly increased in the high cholesterol group and the high cholesterol combined with Hp infection group.And the expression of serum gastrin decreased.The expression of JAK,STAT3 in gastric tissues reduced,as did the expression of COX2.Serum cholesterol levels decreased,with no significant changes in IL-6 levels,but a reduction in IL-8 levels.Compared to the control group,the high cholesterol combined with Hp infection group showed reduced hepatic ballooning degeneration and alleviated gastric tissue inflammation.In addition,inflammation in gastric tissue was also reduced in the cholesterol group and the Hp infection group.Conclusion VD3 alleviates gastritis by enhancing the activity of VDR in liver tissues,blocking the JAK/STAT3 signaling pathway,and inhibiting the expression of inflammatory factors.

关 键 词：维生素D3 维生素D受体(VDR) Janus激酶(JAK) 信号转导子与转录激活子3(STAT3) 高胆固醇血症 幽门螺杆菌(Hp) 

分 类 号：Q565.3[生物学—生物化学] R517.9[医药卫生—内科学] R392-33[医药卫生—临床医学]