上海交通大学学报（医学版）

›› 2012, Vol. 32 ›› Issue (4): 446-.doi: 10.3969/j.issn.1674-8115.2012.04.017

• 论著（基础研究） • 上一篇    下一篇

曲尼司特对肾缺血再灌注损伤小鼠肾脏结构及功能的影响

汪成合, 邵 琨, 王祥慧, 徐 达, 周佩军, 詹嘉铭, 廖炯博   

  1. 上海交通大学 医学院附属瑞金医院肾脏移植中心, 上海 200025
  • 出版日期:2012-04-28 发布日期:2012-04-27
  • 通讯作者: 王祥慧, 电子信箱: wxh4270@sina.com。
  • 作者简介:汪成合（1986—）, 男, 硕士生；电子信箱: swiftarrow2009@163.com。
  • 基金资助:

    卫生部国际交流与合作课题（IHECC07-001）；上海市科委基金上海市器官移植重点实验室研究项目（10DZ2212000）

Effects of Tranilast on renal structure and function in mice with ischemic reperfusion injury

WANG Cheng-he, SHAO Kun, WANG Xiang-hui, XU Da, ZHOU Pei-jun, ZHAN Jia-ming, LIAO Jiong-bo   

  1. Renal Transplantation Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
  • Online:2012-04-28 Published:2012-04-27
  • Supported by:

    Foundation of International Communication and Cooperation of the Ministry of Health of China, IHECC07-001；Shanghai Science and Technology Committee Foundation, 10DZ2212000

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摘要：

目的 探讨吲哚胺-2,3-双加氧酶（IDO）高表达促动剂曲尼司特预处理对肾缺血再灌注损伤（RIRI）小鼠肾脏组织结构及功能的影响及可能的作用机制。方法 C57BL/6小鼠随机分为假手术组、RIRI组、低剂量曲尼司特预处理+RIRI组（建模前给予300 mg/kg 曲尼司特灌胃3 d）和高剂量曲尼司特预处理+RIRI组（建模前给予600 mg/kg 曲尼司特灌胃3 d）。术后24 h，各组小鼠自眼眶后静脉丛采集全血样本后处死，取脾脏和两侧肾脏。自动生化分析系统检测各组肾功能指标血清肌酐（SCr）和血尿素氮（BUN）；流式细胞术检测各组小鼠脾脏组织中辅助性T淋巴细胞1型与2型的分布情况（Th1/Th2）；苏木精-伊红染色后光学显微镜观察肾脏组织病理学改变；分别采用Real-Time PCR技术和Western blotting法检测肾脏组织中IDO mRNA和蛋白的相对表达量；高效液相色谱法测定血清犬尿氨酸和色氨酸浓度，并估算IDO活性。结果 与RIRI组比较，低剂量或高剂量曲尼司特预处理+RIRI组小鼠的SCr、BUN水平及脾脏组织中Th1/Th2显著降低（P＜0.01），肾脏组织病理损害较轻，而肾脏组织中IDO mRNA和蛋白的相对表达量及血清IDO活性显著升高（P＜0.01）；上述改变呈剂量依赖性效应（P＜0.05或P＜0.01）。结论 曲尼司特预处理对RIRI小鼠的肾脏组织结构和功能具有保护作用，其机制可能与促进IDO高表达致免疫负调节有关。

关键词: 曲尼司特, 缺血再灌注损伤, 吲哚胺-2,3-双加氧酶, 肾脏, 小鼠

Abstract:

Objective To investigate the effects of pretreatment with Tranilast, indoleamine 2,3-dioxygenase (IDO) high expression activator on the structure and function of mouse renal tissues with renal ischemic reperfusion injury (RIRI), and explore its possible mechanism. Methods C57BL/6 mice were randomly divided into sham operation group, RIRI group, low dose Tranilast pretreatment+RIRI group (intragastric administration of 300 mg/kg Tranilast for 3 d before model establishment) and high dose Tranilast pretreatment+RIRI group (intragastric administration of 600 mg/kg Tranilast for 3 d before model establishment). Twenty-four hours after operation, blood samples were obtained from the fossa orbitalis vascular plexus in each group, mice were sacrificed, and spleen and kidneys of both sides were obtained. Serum creatinine (SCr) and blood urea nitrogen (BUN) were measured with automatic biochemistry analyzer, the distributions of type 1 helper T lymphocyte and type 2 helper T lymphocyte (Th1/Th2) in spleen tissues of each group were determined by flow cytometry, the pathological changes of renal tissues were observed under light microscope with HE staining, the relative expression of IDO mRNA and protein in renal tissues was detected by Real-Time PCR and Western blotting respectively, serum concentrations of kynurenine and tryphtophan were measured with high performance liquid chromatography, and serum IDO activity was estimated. Results Compared with RIRI group, SCr and BUN levels and Th1/Th2 in spleen tissues in low dose Tranilast pretreatment+RIRI group and high dose Tranilast pretreatment+RIRI group were significantly lower (P＜0.01), the pathological damage in renal tissues was more moderate, the expression of IDO mRNA and protein in renal tissues and serum IDO activity were significantly higher (P＜0.01), and all the above parameters changed in a dosedependent manner (P＜0.05 or P＜0.01). Conclusion Pretreatment with Tranilast has protective effects on the structure and function of renal tissues in mice, and the mechanism may be associated with the high expression of IDO and negative immunoregulation.

Key words: Tranilast, ischemic reperfusion injury, indoleamine 2,3-dioxygenase, kidney, mouse