上海交通大学学报（医学版）

上海交通大学学报（医学版）

• 论著（基础研究） • 上一篇    下一篇

CD4+T细胞极化在单侧输尿管结扎大鼠肾间质纤维化炎症中的作用及机制研究

朱珠1，刘英莉1，韩超楠2，张薇1   

  1. 1.上海交通大学 医学院附属第九人民医院肾脏科， 上海 200011; 2.上海同济大学附属上海市肺科医院, 上海 200082
  • 出版日期:2015-07-28 发布日期:2015-08-27
  • 通讯作者: 张薇, 电子信箱: 18621657463@126.com。
  • 作者简介:朱珠(1989—)， 女， 硕士生; 电子信箱: pearlyzz@163.com。
  • 基金资助:

     国家自然科学基金（31300811）

Effects of polarization of CD4+T cells on inflammation of renal interstitial fibrosis of rats with unilateral ureteral obstruction and relevant mechanisms

ZHU Zhu1, LIU Ying-li1, HAN Chao-nan2, ZHANG Wei1   

  1. 1.Department of Nephrology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China; 2.Department of Oncology, Shanghai Pulmonary Hospital, Tongji University, Shanghai 200082, China
  • Online:2015-07-28 Published:2015-08-27
  • Supported by:

    National Natural Science Foundation of China, 31300811

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摘要：

目的 探究CD4+T细胞极化在肾间质纤维化炎症反应过程中的作用。方法 采用单侧输尿管结扎（UUO）大鼠模型，24只SD大鼠随机分为假手术对照组、UUO 3 d组和UUO 7 d组。利用H-E、MASSON染色技术观察肾组织纤维化程度，采用免疫磁珠分选外周血中CD4+T细胞并在CD3/28-IL-2的刺激下培养3 d，流式细胞术比较UUO大鼠和正常大鼠CD4+T细胞体外增殖、极化情况，PCR法检测转录因子的差异。结果 UUO造模后肾组织纤维化程度以及淋巴细胞的浸润程度加重，CD4+T细胞增殖增加（P<0.05）。造模组IL17A+CD4+T/CD4+T细胞比例和CD4+CD25+Foxp3+/CD4+T比例较正常组表达增加（P<0.05）。检测CD4+T各亚群上游转录因子，发现促炎基因RORγt、T-bet随造模时间显著增加，抑炎基因Gata-3下调，调节炎症的基因Foxp3上调（P<0.05）。结论 肾间质纤维化会促使CD4+T细胞增殖并释放多种促炎因子，加重炎症反应，使病情恶化。

关键词: 单侧输尿管结扎大鼠, 肾间质纤维化, CD4+T细胞, Th17细胞, 调节T细胞

Abstract:

Objective To explore the effects of polarization of CD4+T cells during the course of inflammatory reaction of renal interstitial fibrosis. Methods Twenty-four SD rats that underwent unilateral ureteral obstruction (UUO) were randomly divided into the sham-operation group, UUO 3 d group, and UUO 7 d group. The degree of fibrosis of renal tissue was observed by H-E and MASSON staining. CD4+T cells in peripheral blood were separated by immunomagnetic beads and cultured for 3 d under the stimulation of CD3/28-IL-2. The in vitro proliferation and polarization of CD4+T cells of rats with UUO and normal rats were compared by flow cytometry. The difference of transcription factor was detected by PCR. Results The fibrosis of renal tissue and infiltration of lymphocytes aggravated and the proliferation of CD4+T cells increased after UUO (P<0.05). Compared with normal rats, IL17A+CD4+T/CD4+T and CD4+CD25+Foxp3+/CD4+T ratios of rats with UUO were higher (P<0.05). Detection of upstream transcription factors of CD4+ T subsets showed that pro-inflammatory genes RORγt and T-bet significantly increased with time after UUO; anti-inflammation gene Gata-3 decreased; and inflammation regulation gene Foxp3 increased (P<0.05). Conclusion Renal interstitial fibrosis can promote CD4+T cell to proliferate and release various pro-inflammatory factors and aggravate inflammatory reaction and disease.

Key words: unilateral ureteral obstruction rats, renal interstitial fibrosis, CD4+T cell, Th17 cell, regulatory T cell