辛伐他汀和非诺贝特对小鼠肝脏载脂蛋白M表达的影响及调控机制

目的 探讨辛伐他汀和非诺贝特及两者联合对小鼠肝脏载脂蛋白M（apoM）表达的影响及其机制,为防治动脉粥样硬化提供依据.方法 32只C57BL/6N小鼠按数字表法分为四组,对照组：普通饮食喂养;他汀组：辛伐他汀10 mg/（kg·d）]干预;贝特组：非诺贝特100 mg/（kg·d）]干预;联合组：辛伐他汀10 mg/（kg·d）]和非诺贝特100 mg/（kg·d）]干预,4周后分别检测小鼠肝脏apoM mRNA和蛋白、肝细胞核因子-1α（HNF-1α）mRNA、肝X受体-α（LXRα）mRNA的表达.结果 辛伐他汀和非诺贝特均上调apoM mRNA（1.97±0.04;2.02±0.02）和蛋白、HNF-1α mRNA（1.74±0.05;1.71±0.04）的表达,联合组（3.07±0.03;2.57±0.03）升高程度高于他汀组（1.97±0.04;1.74±0.05）和贝特组（2.02±0.02;1.71±0.04）（P＜0.05）.辛伐他汀下调LXRα mRNA（1.00±0.02）表达（P＜0.05）,非诺贝特上调LXRα mRNA（2.80±0.04）表达（P＜0.05）,联合组LXRα mRNA表达（1.56±0.03）与对照组（1.53±0.03）比较差异无统计学意义（P＞0.05）.结论 辛伐他汀和非诺贝特可上调apoM表达,两者联合疗效更显著;其机制可能与两者调控HNF-1α和LXRα有关.

Effects and mechanism of simvastatin and fenofibrate on the expression of hepatic apolipoprotein M in mice

Objective To examine the effects and mechanisms of simvastatin and fenofibrate, and combination of the two drugs on the expression of apolipoprotein M (apoM). Methods The male C57BL/6N mice ( n =32) were random divided into four groups, including control group (with no special treatment), statin group (with simvastatin 10mg/( kg · d) for 4 weeks], fibrate group (with fenofibrate 100mg/( kg · d) for 4 weeks] and combination group ( with simvastatin 10mg/( kg· d)] and fenofibrate 100mg/( kg · d) for 4 weeks]. The levels of apoMmRNA and protein, hepatic nuclear factor (HNF-1α)mRNA, liver X receptor-α (LXRα) mRNA in mouse liver were measured. Results Both of simvastatin and fenofibrate can increase the expression of apolipoprotein M ( 1.97 ± 0. 04,2. 02 ± 0. 02 ) and HNF-1αmRNA ( 1.74 ± 0. 05,1.71 ± 0. 04). Combination group obtained more effects than either single agent ( P ＜ 0. 05 ). Simvastatin could decrease the expression of LXRα mRNA ( 1.00 ± 0. 02 ) ( P ＜ 0. 05 ). Fenofibrate could increase the expression of LXRα mRNA(2. 80 ±0. 04) ( P ＜0. 05). No significant difference in LXRα expression was seen between combination( 1.56 ±0. 03 ) and control group( 1.53 ±0. 03 )( P ＞0. 05). Conclusions Simvastatin and fenofibrate can increase apoM expression. Treatment with combination of the two drugs is more effective, and the mechanism might be related to the regulation of HNF-1α and LXRα.