IL-17A与自发性高血压大鼠肾上皮间质转化密切相关  

Interleukin-17A is closely correlated with the progression of renal epithelial-mesenchymal transition in spontaneously hypertensive rats

作　　者：向茂翠 王瑜 梅仁彪 付计锋 陈静 都昌乐 XIANG Maocui;WANG Yu;MEI Renbiao;FU Jifeng;CHEN Jing;DU Changle(Department of Medical Functional Sciences,Medical College of Anhui University of Science&Technology,Huainan 232001,China)

机构地区：[1]安徽理工大学医学院医学机能学教研室,安徽淮南232001

出　　处：《南方医科大学学报》2022年第5期772-779,共8页Journal of Southern Medical University

基　　金：安徽高校省级自然科学重点研究项目(KJ2017A098);安徽理工大学博士科研基金(11046);安徽理工大学中青年学术骨干培养工程(10167)。

摘　　要：目的探究IL-17A在原发性高血压大鼠肾上皮间质转化(EMT)中的作用。方法4周龄的SPF级自发性高血压大鼠(SHR)(实验组)、京都维斯塔尔大鼠(WKY)(对照组)各20只,分别随机分为4组,每组5只,在4、6、10、30周龄进行实验观察。采用无创尾动脉血压测量仪动态检测大鼠的血压情况;流式细胞技术分析大鼠脾淋巴细胞中Th17细胞的频数;RT-PCR法及免疫组化技术检测大鼠肾脏IL-17A、iNOS、Arg-1、E-cadherin、α-SMAmRNA和蛋白的表达水平;ELISA法检测大鼠血浆中IL-17A的水平。结果从6周龄始SHR大鼠血压显著高于同期的WKY组(P<0.05或P<0.01),SHR大鼠Th17细胞频数以及肾脏和血浆中IL-17A的表达亦显著高于同期WKY组(P<0.05或P<0.01);在30周龄时SHR大鼠肾脏中E-cadherinmRNA及蛋白的表达显著低于WKY组(P<0.01),而Arg-1 mRNA及蛋白的表达显著高于WKY组(P<0.01);iNOS mRNA及蛋白的表达在6、10周龄时显著高于WKY组(P<0.05或P<0.01),α-SMAmRNA及蛋白从10周龄始显著高于WKY组(P<0.05或P<0.01)。SHR大鼠肾脏中IL-17A mRNA及蛋白表达水平从10周龄始与E-cadherinmRNA及蛋白表达水平呈显著负相关(r=-0.731,P<0.05;r=-0.827,P<0.01),而与α-SMAmRNA及蛋白表达水平呈显著正相关(r=0.658,P<0.05;r=0.968,P<0.01)。结论IL-17A与SHR大鼠肾EMT的过程密切相关,可能是通过介导肾脏浸润的巨噬细胞M1/M2极化发挥作用。Objective To explore the role of interleukin-17A(IL-17A)in renal epithelial-mesenchymal transition(EMT)in essential hypertensive nephropathy.Methods Four-week-old spontaneously hypertensive rats(SHR)and Wistar-Kyoto(WKY)rats(control group)were both randomized into 4 groups(n=5)for observation at 4,6,10 and 30 weeks of age.Blood pressure of the rats was monitored using a noninvasive tail artery blood pressure measurement instrument.The percentage of Th17 cells in the splenocytes was analyzed using flow cytometry.The mRNA and protein expression levels of IL-17A,iNOS,Arg-1,E-cadherin,andα-SMA in the kidneys of the rats were detected using RT-PCR and immunohistochemical staining,respectively,and plasma levels of IL-17A were regularly detected using ELISA.Results At the age of 6 weeks,the SHRs began to show significantly higher blood pressure with greater Th17 cell percentage in the splenocytes and high renal expression and plasma level of IL-17A than WKY rats(P<0.05 or P<0.01).At 30 weeks,renal expression of E-cadherin mRNA and protein was significantly lower and the expression of Arg-1 mRNA and protein was significantly higher in SHR than in WKY rats(P<0.01).Compared with the WKY rats,the SHRs showed significantly higher mRNA and protein expressions of iNOS at 6 and 10 weeks(P<0.05 or 0.01)and higherα-SMA mRNA and protein expressions since 10 weeks of age(P<0.05 or 0.01).In SHRs older than 10 weeks,renal IL-17A mRNA and protein expression levels were negatively correlated with those of E-cadherin(r=-0.731,P<0.05;r=-0.827,P<0.01)and positively correlated with those ofα-SMA(r=0.658,P<0.05;r=0.968,P<0.01).Conclusion IL-17A is closely correlated with the progression of renal EMT in SHR and plays its role possibly by mediating M1/M2 polarization of renal infiltrating macrophages.

关 键 词：IL-17A 高血压 上皮间质转化 巨噬细胞 

分 类 号：R544.11[医药卫生—心血管疾病] R692[医药卫生—内科学]