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目的:研究慢性排斥肾移植受体对自身组织抗原——波形蛋白(vimentin)的细胞和体液免疫反应。方法:近交系Lewis大鼠接受F344大鼠供肾行左侧原位肾移植,7天后对侧肾切除,建立肾移植慢性排斥反应模型。术后每2周检测受体蛋白尿水平,术后第49天与98天取供肾作病理检查,观察慢性移植肾肾病(CAN)进程。术后第14、49、98天收获受体脾细胞,以酶联免疫斑点法(ELISPOT)检测vimentin特异性IFN-γ分泌T细胞的数量;收获受体血清以酶联免疫吸附法(ELISA)检测vimentin特异性抗体水平。自体肾移植Lewis大鼠持续行肾功能检测,第98天收获肾脏、脾脏、血清作病理及免疫检测。结果:同种肾移植受体蛋白尿水平在6周后逐渐升高,49天时病理检查发现肾间质纤维化、肾小管萎缩等典型CAN病变,CAN病情逐渐加重。而自体肾移植大鼠术后98天蛋白尿水平无改变,无CAN病变。经体外vimentin特异性刺激,同种肾移植大鼠IFN-γ分泌T细胞的数量在肾移植后49天明显增多(28.3±2.0 vs.10.1±2.1),98天时其数量显著上升(126.0±10.4vs.26.3±4.1,P<0.01)。而自体肾移植大鼠vimentin特异性IFN-γ分泌T细胞数量无明显变化。同种肾移植大鼠vimentin特异性抗体水平术后14天即显著升高(0.230±0.018 vs.0.063±0.008,P<0.05),并维持在较高水平。而自体肾移植大鼠vimentin特异性抗体水平无明显改变。结论:慢性排斥肾移植受体继发针对自身抗原vimentin的细胞与体液免疫反应,继发自身免疫可能参与CAN的发展。
OBJECTIVE: To investigate the cellular and humoral immune responses to chronic rejection renal transplant recipients for their own tissue antigen vimentin. METHODS: Lewis rats inbred line were transplanted to the left kidney of F344 rats for renal transplantation. The rats were resected in 7 days and the model of chronic allograft rejection was established. Receptor proteinuria levels were measured every 2 weeks after operation, and the kidneys were taken for pathological examination on the 49th and 98th day after operation to observe the progression of chronic allograft nephropathy (CAN). Recipient spleen cells were harvested on the 14th, 49th and 98th day postoperatively, and the number of vimentin-specific IFN-γ secreting T cells was detected by ELISPOT. The serum of recipients was harvested by enzyme-linked immunosorbent assay (ELISA) Detection of vimentin-specific antibody levels. Autologous kidney transplantation Lewis rats continued renal function test, the first 98 days kidney, spleen, serum for pathological and immunoassay. Results: The proteinuria level of allograft recipients increased gradually after 6 weeks. At the 49th day, typical CAN pathological changes such as renal interstitial fibrosis and tubular atrophy were observed. The CAN condition gradually aggravated. However, there was no change in albuminuria in 98 days after autologous kidney transplantation in rats, with no pathological changes of CAN. After stimulation with vimentin in vitro, the number of T cells secreted by IFN-γ in the same kind of kidney transplantation increased significantly (P <0.05) at 49 days after kidney transplantation (28.3 ± 2.0 vs.10.1 ± 2.1) and significantly increased at 98 days (126.0 ± 10.4 vs.26.3 ± 4.1, P <0.01). There was no significant change in the number of T cells secreted by vimentin-specific IFN-γ in autologous kidney transplantation rats. The level of vimentin-specific antibody in the same kind of kidney transplantation rats increased significantly (P <0.05) at 14 days after operation and remained at a high level. However, there was no significant change in the level of vimentin-specific antibody in autologous kidney transplantation rats. CONCLUSIONS: Chronic rejection of renal transplant recipients secondary to cellular and humoral immune responses to the autoantigen vimentin may be involved in the development of CAN following secondary autoimmunity.