中文摘要：

目的研究白蛋白过载对阿霉素肾病小鼠肾脏局部补体C3a-C3a受体（C3a R）信号通路及白细胞介素17（IL-17）的影响,初探白蛋白过载致肾脏损害的免疫学机制。方法 SPF级雄性Balb/c健康小鼠随机分为对照组、阿霉素肾病组（ADR组）、白蛋白过载组（ADR＋BSA组）。所有小鼠行左肾切除术,第2周末构建阿霉素肾病模型,第6周末白蛋白过载组腹腔注射牛血清白蛋白（10 mg/g,5次/周,共4周）。第6、10周末检测24小时尿蛋白、血清生化指标、肾脏组织病理、Real-time PCR及免疫组化法检测肾脏C3a、C3a R、TGF-β1表达,ELISA及免疫组化法检测肾脏IL-17表达。结果第10周末ADR组肾脏C3a、C3a R、TGF-β1、IL-17表达均较对照组增高（P均〈0.05）。第10周末ADR＋BSA组尿蛋白、血清尿素氮水平较对照组及ADR组升高（P均〈0.05）;肾脏组织病理发现肾小球呈局灶节段性硬化及肾小管损害加重;肾脏C3a、C3a R、TGF-β1、IL-17表达较对照组及ADR组增高（P均〈0.05）。结论阿霉素肾病小鼠肾脏局部C3a-C3a R信号通路活化,白蛋白过载致持续大量蛋白尿可进一步活化C3a-C3a R信号通路,同时上调TGF-β1、IL-17表达进而加重肾脏损害。

英文摘要：

Proteinuria is a proposed mechanism of progressive renal failure associated with glomerular disease This study designed to observe the effects of albumin overload on C3a-C3aR signaling pathway and IL-17 expression in adriamycin nephropathy （ADR） mice, and initially explore immunological mechanism of albumin overload-caused kidney damage. SPF healthy male Balb/c mice were randomly divided into control group, ADR group, and ADR with bovine serum albumin overload （ADR＋BSA） group. All mice were uninephreetomized under general anesthesia 2 weeks before setting up ADR model. At the end of the 6th week, ADR＋BSA group received weekly 5 intraperitoneally injections of low endotoxin BSA at a dose of 10 mg/g body weight for 4 weeks. At the end of 6th and 10th week, 24 hours urinary protein, serum biochemical indexes and kidney pathological changes were evaluated. Expression levels of C3a, C3aR and TGF-131 in kidney was measured by real-time PCR and immunohistochemistry; expression of IL-17 in kidney was measured by ELISA and immunohistoehemistry. We found that expression levels of C3a, C3aR, TGF-β1 and IL-17 in ADR group were higher than those in control group （P〈 0.05）. At the end of 10th week, ADR＋BSA group appeared proteinuria and BUN increasing （P〈 0.001）. Under electronic microscope, we observed glomerular sclerosis of focal segmental and renal tubular damage.Expression levels of C3a, C3aR, TGF-β1 and IL-17 in ADR＋BSA group were higher than those in control and ADR group（P〈 0.05）. In conclusion, activation of C3a- C3aR signaling pathway exists in adriamycin nephropathy mice. Albumin overload can produce much proteinuria, which could accelerate the progressive kidney damage. Proteinuria activating theexpression of C3a-C3aR signaling pathway, TGF-β1 and IL-17 in adriamycin nephropathy mice might be the potential mechanism.