可诱导共刺激分子介导的Th17细胞极化对自发性高血压大鼠肾纤维化的影响

Role of inducible costimulatory molecule-mediated Th17 cell polarization in renal fibrosis in spontaneously hypertensive rats

目的探讨可诱导共刺激分子(ICOS)介导的Th17细胞极化在原发性高血压肾损害中的作用。方法 4周龄的自发性高血压大鼠(SHR)随机分为SHR-C组及SHR-I组,分别用0.01 mol/L磷酸缓冲盐溶液(PBS)、ICOS阻断型单克隆抗体干预2周。采用无创尾动脉血压测量仪动态监测大鼠的血压。采用流式细胞技术分析大鼠脾淋巴细胞中Th17细胞的频数变化。RT-PCR法动态检测大鼠肾脏中IL-17A m RNA的表达水平。采用免疫组化技术及ELISA法动态检测大鼠肾脏及血浆中IL-17A和TGF-β1的表达水平。采用Masson染色检测大鼠肾脏病理改变情况。结果 SHR-C组大鼠从第10周始血压显著高于同期的SHR-I组大鼠(P<0.05或P<0.01)。从6周始SHR-C组的大鼠Th17细胞频数显著高于同期SHR-I组(P<0.05)。SHR-C组的大鼠肾脏中IL-17A m RNA表达亦显著高于同期SHR-I组(P<0.05),且其血浆和肾脏中IL-17A、TGF-β1的表达显著高于同期SHR-I组(P<0.05)。与SHR-C组相比,SHR-I组的大鼠肾脏纤维化程度降低,在30周两者差异具有显著性(P<0.05)。结论由ICOS介导的Th17细胞极化在高血压导致的肾纤维化中起重要作用。

Objective To explore the role of inducible costimulatory molecule（ICOS） signaling pathway-mediated Th17 cells polarization in renal damage in essential hypertension. Methods Four-week-old spontaneously hypertensive rats（SHR） were randomly divided into control（SHR-C） group and intervention（SHR-I） group and subjected to intraperitoneal injections of PBS and ICOS monoclonal antibody for 2 weeks, respectively. Blood pressure of the rats was monitored using noninvasive tail artery blood pressure measuring instrument. The percentage of Th17 cells in the splenocytes was analyzed using flow cytometry, and the expression levels of IL-17 A m RNA in the rat＇s kidneys were detected using RT-PCR. The levels of IL-17 A and TGF-β1 in the plasma and kidneys were dynamically detected using ELISA and immunohistochemistry, respectively.Renal pathological changes in the rats were detected using Masson staining. Results At the age of 10 and 30 weeks, the rats in SHR-C group had a significantly higher blood pressure than those in SHR-I group（P〈0.05 or 0.01）. In rats in SHR-C group,Th17 cells percentage in the splenocytes and IL-17 A m RNA level in the kidney was significantly higher than those in SHR-I group from the age of 6 weeks（P〈0.05）. The expressions of IL-17 A and TGF-β1 in the plasma and kidney were significantly higher in SHR-C group than that in SHR-I group at 6 weeks（P〈0.05）. Compared with those in SHR-C group, the rats in SHR-I group showed significant alleviation of renal fibrosis from the age of 30 weeks（P〈0.05）. Conclusion The ICOS signaling pathway-mediated Th17 cells polarization plays an important role in renal fibrosis in hypertensive rats.