芬戈莫德干预大鼠抗Thy-1系膜增生性肾炎的研究

Fingolimod attenuates rat anti-Thy-1 mesangial proliferative glomerulonephritis

目的:观察芬戈莫德(FTY720)对淋巴细胞亚群的影响,并藉此在体内发挥抑制大鼠系膜增生和系膜基质扩张的作用。方法:通过一次性注射抗Thy-1抗体制备大鼠抗Thy-1系膜增生性肾炎模型,同时给予FTY720灌胃干预,观察注射后1,3,7 d大鼠外周血淋巴细胞计数和亚群分类、尿蛋白定量、肾小球系膜增生程度。结果:在注射抗体1 d后,模型组即出现蛋白尿,3 d后可见系膜细胞和基质增生,7 d增生最明显。FTY720干预组在1,3,7 d后均能显著减少外周血淋巴细胞和各淋巴细胞亚群数量;在注射后3 d和7 d,FTY720可以显著减少模型大鼠蛋白尿,减轻肾小球系膜增生程度和细胞外基质扩张。结论:FTY720可以影响外周血淋巴细胞数量和淋巴细胞亚群分布,显著减少模型大鼠蛋白尿,减轻模型大鼠系膜增生和系膜基质扩张,干预抗Thy-1系膜增生性肾炎的发生。

OBJECTIVE To observe whether fingolimod（FTY720）could attenuate rat mesangial proliferation and extracellu- lar matrix expansion in vivo through its influence on lymphocyte subset distribution. METHODS Rat anti Thy-1 mesangial proliferative glomerulonephritis was established through single injection of anti- Thy-1 antibody, meanwhile FTY720 was giveningastrically to rats. Periphery blood lymphocyte count and lymphocyte subset distribution, urine protein excretion, glomerular mesangial proliferation were measured at 1,3 and 7 days after iniection of anti-Thy-1 antibody. RESULTS Proteinuria was found in rat model of anti-Thy-1 mesangial proliferative glomerulonephritis just 1 day post-injection,and mesangial proliferation and mat/ix expansion were found 3 days post-injection and became prominent 7 days after injection. FTY720 significantly re- duced the number of peripheral blood lymphocytes and subset distribution at 1,3 and 7 days post-injection, and attenuated pro- teinuria, mesangial cell proliferation and extracellular matrix expansion at 3 and 7 days after injection. CONCLUSION FTY720 significantly attenuats rat mesangial proliferation and extracellular matrix expansion in anti-Thy-1 mesangial proliferative glo- merulonephritis,perhaps through its influence on periphery blood lymphocyte number and subset distribution.