维生素A缺乏对大鼠肾脏ABCA1介导的脂质外流途径的影响  

Effect of vitamin A deficiency on ABCA1-mediated lipid efflux pathway in rat kidneys

作　　者：阳海平[1] 陈科[2] 张萱[2] 王莉[3] 李翠萃[3] 王莉佳[3] 李秋[1] 

机构地区：[1]重庆医科大学附属儿童医院肾脏免疫科,重庆400014 [2]重庆医科大学附属儿童医院营养研究室,重庆400014 [3]重庆医科大学附属儿童医院免疫研究室,重庆400014

出　　处：《第三军医大学学报》2010年第19期2075-2079,共5页Journal of Third Military Medical University

基　　金：重庆市科委重点项目(CSTC2009BA5080);重庆市卫生局重点项目(2009-1-34)~~

摘　　要：目的探讨维生素A缺乏(vitaminAdeficiency,VAD)大鼠模型肾脏脂质代谢状况及相关分子机制。方法从孕期开始,给予Wistar大鼠正常饮食(正常对照组,维生素A含量为4000IU/kg的饲料),VAD饮食(VAD组,维生素A含量为400IU/kg的饲料),持续至8周后VAD组继续补充维生素A(VAS组,维生素A含量为6500IU/kg的饲料)15d,每组6只。免疫组化分析肾脏载脂蛋白B100(Apo-B100)、三磷酸腺苷结合盒转运体A1(adenosine triphosphate binding cassetteA1,ABCA1)表达,Real-timePCR技术检测肾脏ABCA1、过氧化物酶体增殖物激活受体α(PPARα)、肝X受体α(LXRα)、视黄醇X受体α/β(RXRα/β)mRNA水平。结果免疫组化分析,第8周VAD组肾脏Apo-B100水平(14.27±0.05)明显高于正常对照组(8.25±0.49)(P<0.05);与第8周正常对照组(37.44±0.46)比较,VAD组肾脏ABCA1表达(24.53±0.86)降低(P<0.05)。Real-timePCR检测,与正常组比较,第8周VAD组肾脏ABCA1表达上调,VAD组RXRα/β、LXRαmRNA水平降低,差异有统计学意义(P<0.05),而PPARαmRNA水平无明显改变(P>0.05);以上改变随维生素A补充即恢复至正常水平。结论 VAD可致PPARα/RXRs-LXRα/RXRs-ABCA1介导的脂质外流途径受损而导致大鼠肾脏脂质沉积增多,但及时补充维生素A能有效使肾脏脂质代谢恢复正常。Objective To study the effect of vitamin A deficiency （VAD） on lipid metabolism in a rat kidney model and its related molecular mechanism. Methods Wistar rats were divided into normal control group （ n = 6 ）, VAD group （ n = 6 ）, and vitamin A supplement （VAS） group （ n=6 ）. Rats in normal control group were fed with a diet containing 4 000 IU/kg of vitamin A, rats in VAD group were fed with a diet containing 400 IU/kg of vitamin A, and rats in VAS group were fed with a diet containing 400 IU/kg of vitamin A for 8 weeks followed by a diet containing 6 500 IU/kg of vitamin A for 15 d. Apolipoprotein B100 （Apo-B100） was analyzed with immunohistochemistry. Expression levels of adenosine triphosphate （ATP） binding cassette A1 （ABCA1） in kidneys, peroxime proliferator activated receptor α（PPARcx）, liver X receptor o~ （LXRcx）, and retinoid X receptor-α/β （RXRα/β） mRNA were measured by real-time PCR. Results Immunohistochemistry analysis showed that the Apo-B100 expression level was significantly higher in VAD group than in normal control group（ 14.27 ± 0. 05 vs 8.25±0.49, P 〈 0.05 ） while expression level of ABCA1 was significantly lower in VAD group than in normal control group 8 weeks after treatment with vitamin A （24.53 ±0.86 vs 37.44 ± 0. 46, P 〈0.05）. Real-time PCR showed that the expression level of ABCA1 was higher and the expression level of LXRα, RXRα/β mRNA was lower in VAD group than in normal control group （ P 〈 0.05 ）. No difference was found in expression of ABCA1 and LXRα, RXRα/β mRNA between the two groups. The above changes returned to their normal level after treatment with vitamin A. Conclusion VAD can lead to ABCA1-mediated lipid efflux pathway injury of PPARα/RXRs-LXRα/RXRs, resulting in lipid accumulation in rat kidneys, which would return to its normal level after treatment with vitamin A.

关 键 词：维生素A缺乏 三磷酸腺苷结合盒转运体A1 脂质代谢 肾脏 大鼠 

分 类 号：R591.41[医药卫生—内科学] R322.61[医药卫生—临床医学]