血管生成素样蛋白3参与肾病综合征高脂血症发生的初步探索  

Potential function of angiopoietin-like protein 3 in hyperlipidemia of nephrotic syndrome

作　　者：刘娇娇[1] 徐虹[1] 戴如凤[1] 刘俊朝[1] 沈茜[1] 孙利[1] 刘海梅[1] 方晓燕[1] 翟亦晖[1] 

机构地区：[1]复旦大学附属儿科医院肾脏科,上海201102

出　　处：《中华肾脏病杂志》2015年第9期669-673,共5页Chinese Journal of Nephrology

基　　金：国家自然科学基金（81370814）;复旦大学博士点基金（20130071120089）

摘　　要：目的初步探讨血管生成素样蛋白3（Angptl3）是否参与肾病综合征高脂血症的发生。方法新生小鼠经基因型鉴定得到Angptl3基因敲除鼠（Angptl3^-/-）及对照组野生型鼠（WT）各60只，随机将对照组鼠分为盐酸阿霉素组（WT-ADR组）和生理盐水组（WT-Saline组），Angptl3^-/-鼠（KO鼠）分为盐酸阿霉素组（KO—ADR组）和生理盐水组（KO—Saline组），每组各分为造模前、造模1周、造模2周、造模4周和造模8周5个时间组，各时间组均6只小鼠。实验组一次性尾静脉注射盐酸阿霉素25mg／kg，对照组给予等量生理盐水。自动生化分析仪检测血脂指标（胆固醇、三酰甘油），ELISA法检测小鼠尿液中尿蛋白和尿肌酐水平，实时荧光定量PCR法检测野生型小鼠阿霉素造模后肾组织中Angptl3mRNA表达变化。结果（1）与WT小鼠比较，Angptl3^-/-一小鼠体质量、肾、肝重量及功能均无明显改变；胆固醇（Cho）和三酰甘油（TG）均较低（P〈0．01）。（2）与WT—Saline组比较，WT—ADR组造模第1周出现尿蛋白升高（P〈0．05），血白蛋白降低（P〈0．05），血脂Cho、TG升高（P〈0．05），且血Cho和TG随着造模时间持续升高；Angptl3mRNA水平在造模第1周起显著高于WT-Saline组（P〈0．05），并持续至第8周俨〈0．01）。肾病模型中，Angptl3mRNA的相对表达量与血Cho、TG呈正相关（r=0．885，P〈0．01；r=0．788，P〈0．01）。（3）Angptl3^-/-小鼠ADR造模后，不同造模时间点血脂（Cho、TG）升高程度均显著低于WT-ADR水平（P〈0．05）。结论Angptl3参与肾病综合征高脂血症的发生，敲除Angptl3能一定程度缓解肾病模型血脂紊乱的发生。Objective To explore whether angiopoietin-like protein 3 （Angptl3） is involved in the development of hyperlipidemia in nephrotic syndrome. Methods PCR analysis was carried out to identify the genotypes of Angptl3 Knockout mice. Sixty newborn Angptl3 knockout （KO） mice and wild type （WT） mice were randomly divided into four groups： KO-ADR, KO-Saline, WT-ADR and WT- Saline group. In each group 6 mice at different time points were separately analyzed： the pre-molding, molding 1st, 2nd, 4th, 8th week. WT-ADR and KO-ADR groups were treated with 25 mg/kg ADR once via tail vein injection at day 0; WT-saline and KO-saline groups were injected with the same volume of saline. Automatic biochemical analyzer was employed to test serum cholesterol （Cho） and triglycerides （TG） levels, ELISA method to detect the urine protein and urine creatinine, and real-time fluorescence quantitative PCR to detect the expression of Angptl3 mRNA in the renal tissue. Results （1）There were no significant differences in the weight, morphology or function of the liver and kidney between the KO and WT mice. Compared with WT mice, the levels of Cho and TG obviously decreased in the KO mice （P 〈 0.01）. （2） In the WT-ADR group, urinary protein levels and the levels of Cho and TG increased significantly at 1st week after ADR injection （P 〈 0.05）, while serum albumin level decreased dramatically （P 〈 0.05）. The serum levels of Cho and TG increased gradually during the entire study period. The expressions of Angptl3 mRNA in kidney tissues were up-regulated significantly from 1st week （P〈0.05） to 8th weeks（P〈0.01）. Furthermore, the expression of Angptl3 mRNA was significantly positively correlated with the Cho and TG levels （r=0.885, P 〈 0.01; r=0.788, P 〈 0.01, respectively）. （3）The levels of Cho and TG in the Angptl3^-/- mice were lower than those in the WT mice during the entire study period after ADR injection （P 〈 0.05）. Conclusions Angptl3 is involved in the development

关 键 词：多柔比星 肾病综合征 高脂血症 血管生成素样蛋白3 

分 类 号：R726.9[医药卫生—儿科]