CAJ | 학술논문

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25 mg/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Angptl3 mRNA表达变化. 结果 (1)与WT小鼠比较,Angptl3-/-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;Angptl3 mRNA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(P<0.01).肾病模型中,Angptl3 mRNA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.
목적 초보탐토혈관생성소양단백3(Angptl3)시부삼여신병종합정고지혈증적발생. 방법 신생소서경기인형감정득도Angptl3기인고제서(Angptl3-/-)급대조조야생형서(WT)각60지,수궤장대조조서분위염산아매소조(WT?ADR조)화생리염수조(WT?Saline조),Angptl3-/-서(KO서)분위염산아매소조(KO?ADR조)화생리염수조(KO?Saline조),매조각분위조모전、조모1주、조모2주、조모4주화조모8주5개시간조,각시간조균6지소서.실험조일차성미정맥주사염산아매소25 mg/kg ,대조조급여등량생리염수.자동생화분석의검측혈지지표(담고순、삼선감유),ELISA법검측소서뇨액중뇨단백화뇨기항수평,실시형광정량PCR법검측야생형소서아매소조모후신조직중Angptl3 mRNA표체변화. 결과 (1)여WT소서비교,Angptl3-/-소서체질량、신、간중량급공능균무명현개변;담고순(Cho)화삼선감유(TG)균교저(P<0.01).(2)여WT?Saline조비교,WT?ADR조조모제1주출현뇨단백승고(P<0.05),혈백단백강저(P<0.05),혈지Cho、TG승고(P<0.05),차혈Cho화TG수착조모시간지속승고;Angptl3 mRNA수평재조모제1주기현저고우WT?Saline조(P<0.05),병지속지제8주(P<0.01).신병모형중,Angptl3 mRNA적상대표체량여혈Cho、TG정정상관(r=0.885 , P<0.01;r=0.788 ,P<0.01).(3)Angptl3-/-소서ADR조모후,불동조모시간점혈지(Cho、TG)승고정도균현저저우WT?ADR수평(P<0.05). 결론 Angptl3삼여신병종합정고지혈증적발생,고제Angptl3능일정정도완해신병모형혈지문란적발생.
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 of hyperlipidemia in nephrotic syndrome. Knocking-out of Angptl3 may play an anti-dyslipidemic role in nephrotic syndrome.