TIPE2在肾脏移植排斥反应患者中的表达及临床意义

摘要

Objective To explore the TIPE2 expression and its role in renal transplant rejection recipients. Methods Based on the clinical diagnosis criteria,ninety-six renal transplant patients were divided into 3 groups:acute rejection group(AR,n=32),chronic re-jection(diagnosed by pathology) group(CR,n=33) and long-term survival group(no proteinuria, stable renal function and survival time more than five years)(LTS,n=31). Thirty-two healthy volunteers were used as a control group. Chronic rejection was diagnosed and graded according to the modified Banff 2005 classification scheme. The peripheral blood mononuclear cells( PBMC) and kidney bi-opsy samples were collected. TIPE2 expression in PBMCs and kidney biopsy samples were performed using Western blot and immuno-histochemistry. Lymphocytes were separated from human splenocytes and treated with immunosupressive drug for 72 h. The impact of immunosuppressive agent on TIPE2 expression was determined by RT-PCR. Results Compared with control group,TIPE2 expression in PBMCs decreased in AR group(P<0. 05) but slightly increased in LTS group(P>0. 05), and significantly increased in CR group (P<0. 01). Compared with control group,TIPE2 expression in kidney allograft tissue significantly decreased in CR group(P<0. 05), but slightly decreased in AR group(P>0. 05). CsA inhibited TIPE2 expression in a dose-dependent relationship(P<0. 05), whereas Sir had no effect on its expression. Combination of CsA and Sir also inhibited TIPE2 expression(P<0. 05). Conclusion These re-sults suggest that TIPE2 may involve in organ transplant rejection.%目的 探讨TIPE2在肾脏移植排斥患者中的表达,分析其在移植排斥反应中的作用. 方法 根据临床诊断标准,选取肾移植术后患者96例,其中急性排斥32例,慢性排斥33例(均行移植肾组织病理学诊断) ,肾移植后长期存活31例(存活5年以上,肾功能稳定,无蛋白尿). 32例健康志愿者作为对照组. 用淋巴细胞分离液分离外周血单个核细胞( PBMC) ,用Western blot测定各组TIPE2蛋白的表达;同时用免疫组化法观察各组患者移植肾组织TIPE2表达的差异;用不同剂量的环孢素A和雷帕霉素处理淋巴细胞,用RT-PCR检测免疫抑制剂对TIPE2表达的影响. 结果 与对照组比较,TIPE2在肾移植术后急性排斥反应患者PBMC中表达下降(P<0. 05),但肾脏移植慢性排斥患者则表达明显增高(P<0. 001),肾功能稳定的患者TIPE2的表达轻度升高(P>0. 05). 结果表明TIPE2在急性排斥的移植肾组织中表达较对照组轻度下降(P>0. 05),但慢性排斥移植肾组织中明显降低(P<0. 05). 同时发现环孢素A可抑制TIPE2表达,并呈现剂量依赖的关系(P<0. 05);但雷帕霉素对TIPE2的表达没有影响(P>0. 05);环孢素A和雷帕霉素合用同样抑制 TIPE2 的表达(P<0. 05). 结论TIPE2与肾移植术后急性、慢性排斥反应密切相关,表明TIPE2参与肾移植排斥反应的过程.