C3a、C5a受体缺失减轻IgA肾病肾损伤

Deficiency of C3a/C5a receptors protect kidney from injury in IgA nephropathy

目的：探讨C3a、C5a及其受体在IgA肾病发病中作用及潜在机制。方法：6～8周清洁级雌性BALB／c小鼠28只，阴性对照组、野生型组、C3 a受体敲除组、C5 a受体敲除组各7只，采用有活性的仙台病毒滴鼻经鼻黏膜感染联合尾静脉注射建立小鼠IgA肾病模型，测定24 h尿蛋白量、血清尿素氮、血清肌酐；留取肾组织标本，通过直接免疫荧光法检测肾组织IgA、C3沉积；采用PAS染色光镜下观察肾组织病理改变；采用RT-qPCR法检测肾组织中TNF-α、TGF-β、IL-1β、IL-6、MCP-1 mRNA相对表达量。结果：15周后野生型组、C3a受体敲除组、C5a受体敲除组（实验组）24 h尿蛋白量高于阴性对照组，野生型组高于C3 a受体敲除组及C5 a受体敲除组，差异具有统计学意义；血清尿素氮及血清肌酐差异无统计学意义；实验组小鼠可见肾脏组织病理改变，且野生型组重于C3 a受体敲除组及C5 a受体敲除组，阴性对照组肾脏组织病理则无明显异常。实验组小鼠肾组织TNF-α、TGF-β、IL-1β、IL-6、MCP-1 mRNA相对表达量高于阴性对照组，同时野生型组高于C5a受体敲除组及C3a受体敲除组，另外IL-1β、IL-6、MCP-1的mRNA相对表达量C5a受体敲除组高于C3a受体敲除组。结论：C3a及C5a受体缺失可减轻IgA肾病肾损伤，并且C3a受体缺失作用更加显著。

Objective：To investigate the role of C3a,C5a and their receptors in the pathogenesis of IgA nephropathy （IgAN）. Methods：A total of twenty-eight 6-8 weeks old female BALB/c mice were investigated.And they were negative control group , WT group,C3aR-/-group,C5aR-/-group（the latter three groups were named as experimental groups ）,seven mice in each group.All the mice were infected through respiratory tract with infectious SV （experimental groups） or PBS（negative control group）,combined with tail vein challenge to make IgAN animal model.Testing 24 h total urinary protein , serum urea nitrogen （ BUN ） and creatinine （ Cr ） , using direct immunofluorescence to test the renal deposition of IgA and C 3,observing renal pathologic lesion under PAS staining with light microscopy.RT-qPCR was used to test the relative mRNA expression of TNF-α,TGF-β,IL-1β,IL-6,MCP-1.Results： After 15 weeks,the level of UTP in experimental group was significantly higher than negative control group ,and the same results as WT group than C3aR^-/-group and C5aR^-/-group.There was no significant difference among groups for BUN and Cr.Combined with negative control group , experimental groups had significant renal pathological lesions , and the changes of WT group was more severe than C3aR^-/-group and C5aR^-/-group.The results of relative mRNA expression of TNF-α,TGF-β,IL-1β,IL-6,MCP-1 was the same as the level of 24 h UTP,at the same time,the relative mRNA expression of IL-1β,IL-6,MCP-1 in C3aR^-/-group was significantly less than C5aR^-/-group.Conclusion：The deficiency of C3a/C5a receptors can protect kidney from injury in IgAN ,and C3a receptor has more significant role in protect kidney from injury in IgAN.