肾移植继发自身免疫病理具有组织损伤依赖性

Pathogenicity of subsequent autoimmunity following renal transplantation was based on tissue injury

目的:甄别、测量与评估大鼠肾移植继发自身免疫反应的致病性。方法:使用保留受体自体肾的F344-Lewis大鼠肾移植模型(AI组)、Lewis大鼠自体肾单纯缺血再灌注模型(IR组)、同系移植肾病大鼠脾细胞过继并Lewis大鼠自体肾缺血再灌注模型(AR组),以Lewis大鼠自体肾移植作为对照(Syn组)。术后第10周检测大鼠受体血清vimentin抗体水平,动态监测蛋白尿水平,术后第40周检测自体肾肾小球硬化指数、肾脏IgG沉积。结果:术后第10周AI组和AR组血清vimentin抗体水平比Syn组显著升高(0.312±0.036,0.310±0.017 vs.0.061±0.012),IR组则无明显改变,显示AI组和AR组有自身免疫反应发生。AI及IR组蛋白尿水平至40周维持正常(Proteinuria<0.05 g/mmol)。AR组在第18周出现蛋白尿水平异常(0.18±0.03 g/mmol),其后持续缓慢上升至40周为(0.23±0.04)g/mmol,肾功能变化具有显著性。AR组自体肾在第40周病理检查肾小球硬化指数为(1.24±0.16),并且肾组织IgG沉积呈强阳性。AI组与IR组则未发现自体肾病理损害。结论:大鼠同种肾移植继发的自身免疫基于肾脏缺血再灌注损伤可发展出致病性,对于长期存活的移植肾其损害强度不能忽略。

Objective：To distinguish, measure and evaluate the pathogenicity of subsequent autoimmunity following renal transplantation in rats. Methods： Lewis rats of receiving F344 rat renal transplant as well as reserving the autologous kidney （AI groups） , the autologons kidney following isehemia reperfusion （IR group ） and the autologous kidney following isehemia reperfusion which the host be transferred splenocytes from syngenic rat undergoing chronic allograft nephropathy （AR group） were investigated. Rats of syngenic renal transplants acted as the control group （Syn group）. Vimentin autoimmune antibodies in serum were examined at the l0＇h weeks after operation. Proteinuria dynamic of recipients were observed. Glomerulosclerosis and IgG deposit of autologons kid- ney were examined at the 40th weeks. Results： At the l0th weeks the anti-vimentin IgG response of AI and AR groups significantly in- creased comparing with that of Syn group （0. 312 ± 0. 036, 0. 310 ± 0. 017 vs. 0. 061 ± 0. 012） but not IR group. It supported that the autoimmune responses were existing in AI and AR groups. After 18 weeks the proteinuria of AR group began increasing to （0.18 ± 0.03 ） g/mmol and then developed slowly that reach （0.23 ± 0.04 ） g/mmol at the 40th weeks. The proteinuria changes of AR group were significant. At the 40th weeks in autologous kidney of AR group the glomeruloselerosis index was （ 1.24 ± 0.16） and the IgG antibodies deposited broadly. No pathologic damages were detected in the autologous kidneys of AI and IR groups. Conclusion： The pathogenicity of subsequent autoimmunity following renal transplantation is based on tissue injury and the pathologic intensity eouldn＇ t be neglected for long-term surviving renal allografts.