白蛋白过载加重阿霉素肾病小鼠肾损害及辛伐他汀的肾脏保护作用

发布时间：2018-05-12 05:31

本文选题：蛋白尿 + 炎症　；参考：《中国病理生理杂志》2017年02期

【摘要】：目的:探讨白蛋白过载是否可以通过脂质肾毒性加重阿霉素肾病小鼠肾脏损害及辛伐他汀的肾脏保护作用。方法:雄性BALB/c小鼠随机分为对照组、阿霉素肾病组(ADR组)、白蛋白过载阿霉素肾病组(ADR+BSA组)和白蛋白过载阿霉素肾病辛伐他汀治疗组(ADR+BSA+SIMV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周末开始构建白蛋白过载模型。0、2、6、10、14周末检测24 h尿蛋白;14周末收集标本,检测血清生化指标;光镜和电镜观察肾脏组织病理;酶比色法和油红O染色法检测肾脏组织脂质水平;real-time PCR法检测肾组织IL-1β、TGF-β1和低密度脂蛋白受体(LDLr)的mRNA表达;免疫组化法检测IL-1β和IL-17的蛋白水平;ELISA检测肾组织匀浆上清IL-17的分泌。结果:与对照组相比,ADR组肾组织IL-1β、TGF-β1、IL-17和LDLr的表达增高(P0.05),肾组织内胆固醇含量升高(P0.05)。ADR+BSA组较ADR组尿蛋白及血清肌酐水平增加,IL-1β、IL-17及LDLr表达均显著增加(P0.05),肾组织脂滴沉积及肾小球硬化加重。而ADR+BSA+SIMV治疗组上述炎症因子表达下调,肾组织内胆固醇含量减少,肾小球硬化程度降低。结论:阿霉素肾病小鼠肾组织内炎症介质可能通过上调LDLr导致肾脏局部脂质沉积,加重肾脏损害;白蛋白过载可进一步加重这一进程;而辛伐他汀可通过降低炎症介质及LDLr的表达减少脂质沉积,对肾脏起保护作用。
[Abstract]:Aim: to investigate whether albumin overload can aggravate renal damage and renal protection of simvastatin in adriamycin nephropathy mice by lipid nephrotoxicity. Methods: male BALB/c mice were randomly divided into control group, adriamycin nephropathy group, albumin overload adriamycin nephropathy group (BSA group) and albumin overload adriamycin nephropathy simvastatin treatment group. All mice were treated with left nephrectomy. At the end of the second week, the adriamycin nephropathy model was constructed, and the albumin overload model was constructed at the end of the 6th week. The 24 h urine protein was collected at the end of the 14th week, and the serum biochemical indexes were detected, and the renal histopathology was observed by light microscope and electron microscope. MRNA expression of IL-1 尾 TGF- 尾 1 and low density lipoprotein receptor (LDLR) in renal tissue was detected by real-time PCR method, and the protein levels of IL-1 尾 and IL-17 were detected by immunohistochemical method and the secretion of IL-17 in renal homogenate was detected by enzyme-linked immunosorbent assay (Elisa). Results: compared with the control group, the expression of IL-1 尾 -TGF- 尾 1tGF- 尾 1 IL-17 and LDLr in renal tissue was higher than that in the control group. The increase of cholesterol content in renal tissue was P0.05. The level of urinary protein and serum creatinine in ADR group was significantly higher than that in ADR group. The expression of IL-17 and LDLr in renal tissue was significantly increased than that in ADR group, and lipid droplet deposition in renal tissue was significantly increased. And glomerulosclerosis. In ADR BSA SIMV treatment group, the expression of above inflammatory factors was down-regulated, the cholesterol content in renal tissue was decreased, and the degree of glomerulosclerosis was decreased. Conclusion: the inflammatory mediators in renal tissue of adriamycin nephropathy mice may lead to the accumulation of local lipid in the kidney by upregulation of LDLr and aggravate the renal damage, which can be further aggravated by albumin overload. Simvastatin can protect the kidney by reducing the expression of inflammatory mediators and LDLr.
【作者单位】：重庆医科大学附属儿童医院肾脏内科儿童发育疾病研究教育部重点实验室儿童感染免疫重庆市重点实验室儿童发育重大疾病国家国际科技合作基地;
【基金】：国家自然科学基金资助项目(No.81270802);国家自然科学基金青年科学基金资助项目(No.81200520)
【分类号】：R692

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