高脂状态对大鼠动脉血管紧张素Ⅱ1型受体mRNA及一氧化氮的影响

Impact of hyperlipidemia on aortic angiotensin Ⅱ type 1 receptor mRNA expression and nitrogen monoxidum in rats

目的观察高脂饮食对大鼠动脉血管紧张素Ⅱ1型受体(angiotensinⅡ1,AT1)mRNA表达、血清一氧化氮(nitrogen monoxidum,NO)水平的影响及降脂治疗的作用,探讨高脂饮食诱导内皮功能障碍的可能机制。方法将30只SD大鼠按电脑数字随机法分为3组,每组10只:正常对照组、高脂血症组和高脂血症治疗组。高脂血症组持续高脂喂养,高脂血症治疗组4周后在高脂喂养同时喂服辛伐他汀10mg/(kg·d),高脂血症组不予药物治疗。第20周末检测3组的血清脂蛋白浓度及AT1mRNA表达水平、血清AngⅡ和NO浓度。结果高脂血症组和高脂血症治疗组第4周末血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇浓度均高于正常对照组,差异有统计学意义(P>0.05)。第20周末,高脂血症治疗组血清总胆固醇、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇浓度低于高脂血症组差异有统计学意义(P>0.05)。3组第20周末收缩压比较,差异无统计学意义[(126±14)mm Hg vs.(127±13)mm Hg vs.(125±13)mm Hg,P>0.05;1mm Hg=0.133kPa]。方差分析显示,3组第20周末血清NO2-/NO3-浓度[(38.0±9.9)μmol/L vs.(29.6±7.2)μmol/L vs.(35.8±9.5)μmol/L,P<0.05]、主动脉组织AT1mRNA表达水平(0.66±0.05vs.0.75±0.08vs.0.70±0.06,P<0.05]差异有统计学意义;3组血清AngⅡ浓度比较差异无统计学意义(P>0.05)。相关分析结果显示,AT1mRNA表达水平与血清总胆固醇、三酰甘油浓度呈显著正相关(r=0.708,P<0.05;r=0.656,P<0.05)。结论高脂可能通过上调AT1受体表达和抑制NO活性而损伤血管,他汀类药物则可逆转这种状态,有利于阻止动脉硬化的发生发展。

Objectives To investigate the impact of hyperlipidemia on aortic angiotensin Ⅱ （Ang Ⅱ ） type 1 receptor （AT1）mRNA expression and nitrogen monoxidum（NO） in rats and study the effect of the statin therapy. Methods We divided 30 SD rats into 3 groups by randomized method： 10 rats in control group, 10 in hyperlipidemic group and 10 in simvastatin treated group. Hyperlipidemic rats were set on a consistent atherogenic diet in hyperlipidemic group, besides, hyperlipidemic models were set up on the 4-week athcrogenic diet and then followed by a 16-week treatment of simvastatin in the simvastatin treated group [simvastatin 10 mg/（kg ·d）]and without treatment in the hyperlipidemic group. The serum lipid level, expression of ATI mRNA of aorta and level of serum Ang Ⅱ and NO were measured in the end of the 20th week. Results After 4 weeks, serum concentrations of total cholesterol （TC）, triglycerides （TG）, low density lipoprotein cholesterol （LDL-C）, high density lipoprotein cholesterol （HDL-C） of hyperlipidemic group and simvastatin treated group were higher than those of control group （P〈0.05）. After 20 weeks, serum concentrations of TC ,TG, LDL-C, HDL-C of simvastatin treated group were significantly lower than those of hyperlipidemic group （P〈 0.05）.After 20 weeks, analysis of variance indicated that systolic blood pressure among the 3 group had no significant difference [（126±14）mm Hgvs.（127±13）mm Hgvs.（125±13）mm Hg,P〉0.05; 1 mm Hg=0.133 kPa]; serum concentrations of NO2^-/NO3^- among the 3 groups had significant difference [ （38.0±9.9）μmol/L vs. （29.6±7.2）μmol/L vs. （35.8±9.5）μmol/L,P〈0.05] ;aortic AT1 mRNA expression among the 3 groups had significant difference （0.66±0.05 vs. 0.75±0.08 vs.0.70±0.06,P〈0.05] ; serum concentrations of Ang Ⅱ among the 3 group had no significant difference （P〉0.05）. Correlation analysis indicated that aortie AT1 mRNA expression was postively correlated with serum concentration of TC and TG（r=0.708, P〈0.05 ; r=0.656,P〈0.05）. Conclusions Hyperlipidernia could upregulate AT1 mRNA expression and inhibit the NO activity so that impaired the endothelial function which simvastatin could restore.