NF-κBp65在口服诱导免疫耐受防治主动性Heymann肾炎中的作用

The role of NF-κB p65 in prevention of actived Heymann nephritis by oral tolerance

目的探讨口服诱导免疫耐受对主动性Heymann肾炎(AHN)的防治作用及机制。方法6～8周龄Wistar雌性大鼠30只平均分3组,AHN模型组和口服诱导免疫耐受组大鼠分别予PBS、Fx1A灌胃,然后皮下免疫Fx1ACFA,同时设正常对照组。观察大鼠迟发性超敏反应(DTH)、肾组织的病理变化、尿蛋白水平,并用SandwichELISA法和免疫组化染色分别观察大鼠脾淋巴组织和肾小球内核因子NFκBp65的活化。结果与正常对照组大鼠比较,AHN模型组和口服诱导免疫耐受组大鼠迟发性超敏反应均明显增强,肾小球基底膜(GBM)明显增厚、尿蛋白水平明显增多,肾小球内和脾淋巴组织NFκBp65的活化明显增加,但与AHN模型组比较,口服诱导免疫耐受组DTH明显减低,尿蛋白水平减低,肾组织病变程度和NFκBp65的活化程度有所减轻,差异有显著性(P<0.01);肾小球内NFκBp65的阳性细胞数与脾淋巴组织NFκBp65活性和肾小球基底膜厚度呈明显的直线正相关(P<0.05)。结论口服诱导免疫耐受减轻了AHN肾小球的病理损害,可能与口服诱导免疫耐受对脾淋巴细胞和肾小球内细胞NFκBp65的活化的抑制作用有关。

Objective To study the preventive effect and the mechanism of actived Heymann nephritis by oral tolerance. Methods Thirty female Wistar rats of 6-8 weeks of age were included. After being administration of Fx1A or PBS by intragastric intubation, nephritis was induced with Fx1A/CFA by subcutaneous injection, and with CFA as a control. We observed DTH,renal pathological changes,levels of urinary protein, the activity of NF-κB p65 in renal and splenic lymph tissue by immune histochemistry staining and Sandwich ELISA respectively. Results Compared with the control group, DTH,the thickness of GBM, levels of urinary protein, the activity of NF-κB p65 in splenic lymph tissue and glomerulus increased significantly in oral tolerance group and AHN model group; however, compared with AHN model group, all of these parameters declined significantly in oral tolerance group. A positive correlation between the number of NF-κB p65 positive cells in renal glomerulus and the activity of p65 in splenic lymphocytes was found. Conclusion A declined activation of NF-κB p65 in splenic lymphocytes and in renal glomerular cells after oral tolerance may play an important role in the prevention of AHN.