摘要
目的 探讨硫氧还蛋白相互作用蛋白（thioredoxin interaction protein,TXNIP）对肾脏纤维化的作用。方法 将12只SPF级C57BL/6J小鼠和12只TXNIP基因敲除鼠（TXNIP^-/-）均按随机数字表法分为2组：正常对照组（normal control group,NC组）和高脂饮食组（high-fat diet group,HFD组）,喂养16周后取其肾组织,用HE、PAS及Masson染色方法观察肾脏组织病理变化及纤维化改变,采用免疫荧光法检测α-平滑肌肌动蛋白（α-SMA）在肾脏组织的表达水平,并通过Western blot检测肾脏组织中TXNIP、TGF-β1、α-SMA、p38 MAPK及p-p38 MAPK的表达情况。结果NC组与HFD组中TXNIP^-/-小鼠的肾脏纤维化程度及p-p38 MAPK蛋白表达水平均明显低于C57BL/6J小鼠（P 〈0. 05）;而C57BL/6J小鼠HFD组与NC组相比,TXNIP在肾脏表达明显上调,且肾脏纤维化及p38磷酸化水平明显增加（P 〈0. 05）。结论 硫氧还蛋白相互作用蛋白可能促进高脂诱导下肾脏纤维化,其作用机制可能与激活p38 MAPK信号通路有关。
Objective To investigate the role of thioredoxin-interacting protein （TXNIP） in high-fat diet-induced renal fibrosis. Methods Specific pathogen-free C57BL/6J mice and TXNIP knockout mice （TXNIP^-/-） were both randomly divided into normal control group and high-fat diet group. After 16 weeks of feeding, the mice were sacrificed and the kidneys were dissected to observe the pathological changes and fibrotic changes using HE, PAS and Masson staining. The expression of α-smooth muscle actin （α-SMA） in the renal tissue was detected using immunofluorescence assay; Western blotting was used to detect the expression of TXNIP, α-SMA, transforming growth factor-β1 （TGF-β1）, p38 mitogen-activated protein kinase （p38 MAPK） and its phosphorylation （p-p38 MAPK） in the renal tissue. Results TXNIP^-/- mice fed on both normal and high-fat diet showed significantly lower expression levels of p-p38 MAPK and milder renal fibrosis than C57BL/6J mice （P 〈 0.05 ）. Compared with the normal control mice, C57BL/6J mice fed on high-fat diet had significantly increased expression of TXNIP and p-p38 MAPK in the kidneys and more obvious renal fibrosis （P 〈 0.05 ）. Conclusion TXNIP plays a role in promoting renal fibrosis in mice fed on high-fat diet, and its mechanism may involve the activation of p38 MAPK signaling pathway.
作者
何其睿
李杨
邓文珍
刘东方
HE Qirui;LI Yang;DENG Wenzhen;LIU Dongfang(Department of Endocrinology,the Second Affiliated Hospital of Chongqing Medical University,Chongqing,400010,China)
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2018年第22期2061-2067,共7页
Journal of Third Military Medical University
基金
国家自然科学基金面上项目(81370467)
重庆市卫生和计划生育委员会科研项目(2016ZDXM011)
重庆市社会事业与民生保障科技创新专项(CSTC2017shmsA130069)~~
