雌激素调节Th17/Treg细胞免疫平衡抑制肾脏缺血再灌注损伤  

Estrogen regulates Th17/Treg cell immune balance to inhibit renal ischemia reperfusion injury

作　　者：张洋[1] 冀伟[1] 周奥飞 常越辰 张亮[1] 马克涛[1] 李丽[1] 司军强[1] 王洋[1] ZHANG Yang;JI Wei;ZHOU Ao-Fei;CHANG Yue-Chen;ZHANG Liang;MA Ke-Tao;LI Li;SI Jun-Qiang;WANG Yang(Department of Physiology,Shihezi University Medical College,Shihezi 832002,China)

机构地区：[1]石河子大学医学院生理教研室,石河子832002 [2]石河子大学医学院第一附属医院泌尿外科,石河子832002

出　　处：《中国免疫学杂志》2018年第11期1601-1606,共6页Chinese Journal of Immunology

基　　金：本文受国家自然科学基金(No.81560175和No.81260159);石河子大学高层次人才研究项目(No.RCSX201705);自治区研究生科研创新项目(No.XJGRI2017033)资助。

摘　　要：目的:探讨雌激素(Estrogen,E_2)对肾脏缺血再灌注损伤的作用及机制。方法:24只雌性SD大鼠随机分为4组:对照组(Control group)、去卵巢组(OVX group)、去卵巢后缺血再灌注损伤组(OVX+IRI group)和雌激素干预组(OE+IRI group)。各组大鼠分别于再灌注后6 h收集血液标本和肾脏组织标本,运用全自动生化分析仪检测肾功能;采用苏木素-伊红(HE)染色和Paller评分量化肾脏损害程度;应用流式细胞和ELISA技术检测外周血中CD3^+CD4^+T淋巴细胞的阳性表达率及细胞因子IL-17、IL-10的血清学水平。结果:在肾脏IRI早期,大鼠血尿素氮(BUN)、血肌酐(SCr)水平和肾脏组织损害程度均高于OVX组(P<0. 01),而经E_2补充治疗后上述指标明显降低(P<0. 05);与OVX组比较,OVX+IRI组中CD3^+CD4^+T细胞阳性表达率和Th17细胞分泌的IL-17的浓度均明显升高(P<0. 01),Tregs分泌的IL-10的浓度减少(P<0. 05);而在OE+IRI组中,CD3^+CD4^+T细胞阳性表达率和IL-17的浓度降低(P<0. 01),IL-10的浓度升高(P<0. 05);此外,相关性分析显示细胞因子IL-17与BUN、SCr和肾脏Paller评分呈正相关性,而细胞因子IL-10与上述指标呈负相关性。结论:Th17/Treg的平衡破坏可能是肾脏IRI早期炎症反应的主要致病因素; E_2可减轻肾脏IRI,其机制可能是通过调节Th17/Treg的平衡从而抑制由IRI诱发的炎症反应。Objective:To investigate the protective effect of estrogen(E 2)on renal ischemia-reperfusion injury(IRI)and its mechanism.Methods:Twenty-four female Sprague-Dawley(SD)rats were randomly divided into 4 groups:normal rats(Control group),ovariectomized rats(OVX group),ovariectomized rats with IRI(OVX+IRI group)and estrogen-replaced ovariectomized rats with IRI(OE+IRI group).Blood samples and kidney samples were collected at 6 hours after reperfusion in rats of each group,and blood urea nitrogen(BUN)and serum creatinine levels were detected by automatic biochemical analyzer.Hematoxylin-eosin(HE)staining and Paller score were used to quantify the degree of renal damage.Flow cytometry and ELISA were used to detect the positive rate of CD3+CD4+T lymphocytes and the serum levels of IL-17 and IL-10 in peripheral blood.Results:In the early stage of renal IRI,the levels of blood urea nitrogen(BUN),serum creatinine(SCr)and the degree of renal tissue damage in rats were higher than those in OVX group(P<0.01),but the above indicators were significantly decreased after E 2 replacement therapy(P<0.05).Compared with OVX group,the expression of CD3+CD4+T lymphocytes and the concentrations of IL-17 secreted by Th17 cells in OVX+IRI group were increased(P<0.01),the levels of IL-10 secreted by Tregs were decreased(P<0.05).While the positive rate of CD3+CD4+T cells and the concentration of IL-17 were significantly decreased(P<0.01),the levels of IL-10 increased(P<0.05)in the OE+IRI group.In addition,correlation analysis showed that there was a positive correlation between IL-17 and BUN,SCr and renal Paller score,while IL-10 was negatively correlated with them.Conclusion:Th17/Treg balance destruction may be one of the main risk factors of early inflammatory reaction in renal IRI.The protective effect of estrogen on renal IRI may be involved in regulating the balance of Th17/Treg cells and inhibiting the inflammatory response.

关 键 词：雌激素 肾脏缺血再灌注损伤 炎症反应 IL-17 IL-10 

分 类 号：R392.32[医药卫生—免疫学]