CD40/CD40L和B7-1/CD28在小鼠叶酸性肾病中的作用

目的研究CD40／CD40L、B7—1／CD28在肾小管间质浸润的免疫活性细胞、损伤的肾组织固有细胞上的表达以及其可能的作用。方法一次性腹腔注射叶酸制作CD1小时鼠叶酸性肾病模型。在第1、2、3、7、14、21天分别处死动物，取其右肾进行免疫组织化学染色；取左肾提取蛋白进行蛋白印迹分析；采血检测BUN、Scr。以抗B7—1功能性单克隆抗体（B7-1mAb）联合叶酸应用，观察21d后，采血行BUN、Scr检测，病理图像分析肾病变区域及保护率。结果小鼠在给予叶酸后第1天，CD40、B7-1在肾小管上皮表达上调，并持续至第21天。通过蛋白印迹半定量检测，CD40在各时间点实验组肾组织表达量均增加5倍以上（P均〈0．01），在间质区域浸润的免疫活性细胞上可见CD28和CD40L的表达。经B7-lmAb干预性治疗，小鼠死亡率从47．83％下降到11．01％。P〈0．01；BUN、Scr水平明显降低；肾组织保护率从7．45％上升至66．51％。结论在小鼠叶酸性肾病中．肾组织CD40／CD40L和B7-1／CD28的表达上调并参与了肾小管上皮细胞损伤、免疫活性细胞浸润和肾小管间质纤维化的过程。B7-1mAb干预治疗能减轻上述的肾损害，为肾间质纤维化的特异性免疫治疗提供新的途径。

Expression and role of CD40/CD40L and B7-1/CD28 interaction in folic acid-induced nephropathy

Objective To explored the role of CD40/CD40L and B7-1/CD28 interaction in the immunopathologic process of folic acid-induced nephropathy(FAN) and investigate the intervention effect of the anti-B7-1 monoclone antibody(B7-1mAb). Methods GD1 mice were administrated by i. p with FA only or co-treated with B7-1 mAb for the intervention study. Kidneys were harvested for immunohistochemical, Western blot assays and serum for renal function evaluation at day 1, 3,5, 7, 14 and 21. Results Continuous expression of CD40, B7-1 from day 1 to day 21 on the renal tubular epithelial cells was detected in this model. CD40 was up-regulated more than five times in the kidney at every test time point (P < 0.01 for all) by semi-quantified of Western blotting. CD28 and CD40L were also observed in the infiltration of immunocopetent cell in the tubulointersititial area. After 21 days observation, death rate decreased from 47.83% to 11.01%(P < 0.01), the renal tissue protection area increased from 7.45% to 66.51% (P < 0.01) and plasma BUN and Scr level decreased. Conclusions The expression of CD40/CD40L and B7-1/CD28 can be detected in FAN. CD40/CD40L and B7-1/CD28 participate in renal tubular epithelial cell injury, immunocompetent cell infiltration and renal tubulointerstitial fibrosis. The success of B7-1mAb intervention provides special immune therapeutic targets for renal fibrosis.