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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。
Objective To investigate the effects of albumin overload on the C3a-C3a receptor (C3aR) signaling pathway and interleukin-17 (IL-17) in adriamycin-induced nephropathy mice and to explore the immunological mechanism of renal damage induced by albumin overload . Methods SPF male Balb / c mice were randomly divided into control group, adriamycin nephropathy group (ADR group) and albumin overload group (ADR + BSA group). Left nephrectomy was performed in all mice. Adriamycin nephropathy model was established at the end of the second week. Bovine albumin (10 mg / g, 5 times / week for 4 weeks) was injected into the albumin overload group on the 6th week. Serum urinary protein, serum biochemical indexes and pathological changes of renal tissues were detected at the 6th and 10th week. The expressions of C3a, C3a R and TGF-β1 in kidney were detected by Real-time PCR and immunohistochemistry. The levels of IL- 17 expression. Results The expression of C3a, C3a R, TGF-β1 and IL-17 in the kidney of ADR group was higher than that of the control group on the 10th week (all P <0.05). At the end of the 10th week, urinary protein and serum urea nitrogen in ADR + BSA group were higher than those in control group and ADR group (all P <0.05). Renal glomerulus showed focal segmental sclerosis and renal tubular damage in renal tissue pathology. C3a, C3a R, TGF-β1 and IL-17 were significantly higher than those in control group and ADR group (all P <0.05). Conclusions Activation of the C3a-C3a R signaling pathway in the kidney of adriamycin-induced nephropathy mice and sustained massive albumin overload may activate the C3a-C3a R signaling pathway and up-regulate the expression of TGF-β1 and IL-17, thereby aggravating renal damage.