高盐饮食激活肠JAK1/STAT3通路诱导肠上皮屏障功能障碍  

High⁃salt diet induces intestinal epithelial barrier dysfunction by activating intestinal JAK1⁃STAT3 signaling pathway

作　　者：李晨 李晓媚[1] 刘亭 雷超 刘聪 刘志华 LI Chen;LI Xiaomei;LIU Ting;LEI Chao;LIU Cong;LIU Zhihua(Department of Innovation Centre for Advanced Interdisciplinary Medicine,the Fifth Affiliated Hospital of Guangzhou Medical University,Guangzhou Key Laboratory of Enhanced Recovery after Abdominal Surgery,Department of Anorectal Surgery,the Fifth Affiliated Hospital of Guangzhou Medical University,Guangzhou 510700,China)

机构地区：[1]广州医科大学附属第五医院前沿医学交叉研究中心,广州市加速康复腹部外科重点实验室,广州医科大学附属第五医院肛肠科,广州510700

出　　处：《实用医学杂志》2021年第1期35-40,共6页The Journal of Practical Medicine

基　　金：广州市教育局创新团队项目(编号:201831828);国家自然科学基金(编号:81670480);广东省自然科学基金(编号:2018A030310168);广东省教育厅2017年重点平台及科研项目(编号:2017KZDXM068);广州市科技和创新委员会产业技术重大攻关项目(编号:201902020001);科技部重大新药创制国家科技重大专项(编号:2020ZX09201026);广州市科技计划项目(编号:201905010004)。

摘　　要：目的探讨高盐饮食在肠道屏障功能中的作用机制与Janus激酶1和转录激活因子3(Janus kinase1⁃signal transducer and activator of transcription 3,JAK1⁃STAT3)信号通路激活的关系。方法将8周的SPF级C57BL/6小鼠随机分成正常饮食对照组(control)和高盐饮食组(high salt diet,HSD)。正常饮食对照组喂养普通饲料,高盐饮食组采用NaCl含量为8%的饲料喂养12周,收集两组小鼠肠道组织,检测屏障蛋白及JAK1/STAT3通路;将人正常结肠上皮细胞NCM⁃460细胞分组如下:(1)正常对照组(control);(2)高浓度NaCl处理组(high NaCl,50 mmol/L),处理时间均为48 h;(3)JAK1抑制剂Ruxolitinib治疗组(high NaCl+Ruxoli⁃tinib),用Ruxolitinib(50μmol/L)预处理2 h,再用NaCl(50 mmol/L)共孵育46 h,通过Western blot法检测细胞屏障蛋白及JAK1/STAT3通路蛋白变化。结果高盐饮食不仅降低小鼠体重、结直肠重和肠长度,还抑制肠屏障蛋白ZO⁃1的相对表达,并上调肠道JAK1磷酸化蛋白;细胞实验中,JAK1抑制剂Ruxolitinib可抵抗由高浓度NaCl诱导的肠屏障功能障碍。结论高盐饮食可能通过激活JAK1/STAT3信号而诱导肠屏障功能障碍。Objective The aim of this study was to investigate whether the mechanism of high⁃salt diet in intestinal barrier function was related with the activation of the signaling pathway of Janus kinase 1⁃signal transducer and activator of transcription 3(JAK1⁃STAT3).Methods SPF C57BL/6 mice weighing(20±5)g were randomly divided into control group and high salt diet(HSD)group.There were 5 mice in each group.Control group was fed with standard chow ad libitum,while the high⁃salt diet was achieved by feeding a dietary chow consisting of 8%NaCl for 12 weeks.At the end of feeding,the intestinal tissue samples were collected to analyze the intestinal barrier function and the activity JAK1⁃STAT3 signaling pathway.Human normal colon epithelial cell line NCM⁃460 was used for cell experiments:(1)Control group(Control);(2)High salt treatment group(High NaCl,50 mmol/L)for 48 h;3)JAK1 inhibitor Ruxolitinib treatment group(High NaCl+Ruxolitinib),pretreatment with JAK1 inhibi⁃tor Ruxolitinib(50μmol/L)for 2 hours,then add high concentration NaCl(50 mmol/L)and incubate for 46 hours.After the cells were processed,the cells were collected to detect the intestinal epithelial barrier tight junc⁃tion proteins and the changes of JAK1⁃STAT3 signaling pathway proteins by Western blot.Results High⁃salt diet could inhibit the expression of intestinal barrier protein and increase the permeability of intestinal barrier as well as activate the expression of JAK1⁃STAT3 signaling pathway protein in the intestinal tissue.JAK1 inhibitor Ruxolitinib resisted intestinal barrier dysfunction induced by high concentration of NaCl.Conclusion High⁃salt diet may induce intestinal barrier dysfunction by activating JAK1-STAT3 signaling.

关 键 词：高盐 JAK1-STAT3通路 肠上皮屏障功能 

分 类 号：R333[医药卫生—人体生理学]