南方医科大学学报 ›› 2022, Vol. 42 ›› Issue (5): 772-779.doi: 10.12122/j.issn.1673-4254.2022.05.21

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IL-17A与自发性高血压大鼠肾上皮间质转化密切相关

向茂翠,王 瑜,梅仁彪,付计锋,陈 静,都昌乐   

  1. 安徽理工大学医学院医学机能学教研室,安徽 淮南 232001
  • 出版日期:2022-05-20 发布日期:2022-06-02

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

XIANG Maocui, WANG Yu, MEI Renbiao, FU Jifeng, CHEN Jing, DU Changle   

  1. Department of Medical Functional Sciences, Medical College of Anhui University of Science & Technology, Huainan 232001, China
  • Online:2022-05-20 Published:2022-06-02

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-SMA mRNA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-cadherin mRNA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-SMA mRNA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-cadherin mRNA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-SMA mRNA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。

关键词: IL-17A;高血压;上皮间质转化;巨噬细胞

Abstract: 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, and α-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 higher α-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 of α-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.

Key words: interleukin-17A; high blood pressure; epithelial-mesenchymal transition; macrophages