叶酸及不同剂量瑞舒伐他汀对HHcy小鼠动脉粥样硬化相关基因表达的影响

摘要

Objective To explore the influence of different doses of rosuvastatin and folic acid on the expression of atherosclerosis(AS)related gene for hyperhomocysteinemia(HHcy) mice.Methods Forty-six mice were randomly divided into five groups.Control group(n=6)was given with ordinary diet.High methionine group(n=10)was given with 2% methionine+ordinary diet,folic acid group(n=10)was given with 0.8 mg/kg folic acid by gavage and 2% methionine after methionine for 4 weeks.Rosuvastatin group of low dose(n=10),high dose(n=10)was given with 0.8 mg/kg,1.6 mg/kg rosuvastatin by gavage and 2% methionine after methionine for 4 weeks.All mice were executed by drawing-out blood after 1 2 weeks,the serum Hcy,blood lipid indicators including TG,TC,HDL-C,LDL-C,hsCRP,TNF-α,MMP-9,the expression of AS related genes including CXCL1,ICAM-1,VCAM-1 were detected.Results The level of HHcy in high methionine group,folic acid group,low dose group was higher than that of control group,and folic acid group,low dose group and high dose group was lower than high methionine group,high dose group was lower than folic acid group(P＞0.05).The level of TC in high methionine group,folic acid group,low dose group was higher than that of control group,and folic acid group,low dose group and high dose group was lower than high methionine group,high dose group was lower than folic acid group and low dose group(P＞0.05).The level of TG in high methionine group was higher than that of control group,and high dose group was lower than high methionine group(P＞0.05).The level of LDL-C in high methionine group,folic acid group,low dose group was higher than that of control group,and folic acid group,low dose group and high dose group was lower than high methionine group,high dose group was lower than folic acid group and high dose group(P＞0.05).The level of HDL-C in high methionine group,folic acid group,low dose group was lower than that of control group,and high dose group was higher than high methionine group,folic acid group and low dose group(P＞0.05). Compared with control group,high methionine group,folic acid group,low dose group and high dose group had higher levels of serum hsCRP,TNF-α,lower level of MMP-9(P＞0.05).The inflammatory indicators in high dose group were significantly lower than those in high methionine group,folic acid group and low dose group(P＞0.05).The percentages of positive cells of CXCL1,ICAM-1,VCAM-1,MMP-9 in aorta tissue of high methionine group,folic acid group, low dose group and high dose group were significantly lower than those in control group(P＞0.05).Compared with folic acid group,low dose group,the percentages of positive cells of AS related genes including CXCL1, ICAM-1, VCAM-1,MMP-9 in high dose group were significantly lower than those in high methionine group,folic acid group,low dose group(P＞0.05).There was no statistically significant difference in the percentages of positive cells of AS related genes between folic acid group and low dose group(P＜0.05).Conclusion High methionine diet can induce Hhcy in mice,and high dose of rosuvastatin can contribute to reduce the level of serum Hcy,improve blood lipid disorder,and down-regulate the expression of AS related genes.%目的 探讨叶酸及不同剂量瑞舒伐他汀对高同型半胱氨酸(hyperhomocysteinemia,HHcy)小鼠动脉粥样硬化(atherosclerosis,AS)相关基因表达的影响.方法 将46只小鼠随机分为5组:对照组(n=6)给予普通饲料喂养;高蛋氨酸组(n=10)给予普通饲料喂养+质量分数2%的蛋氨酸;叶酸组(n=10)在高蛋氨酸饲料喂养4周后,给予0.8 mg/kg叶酸灌胃,同时持续高蛋氨酸饮食;瑞舒伐他汀低剂量组(n=10)、高剂量组(n=10)在高蛋氨酸饲料喂养4周后,给予瑞舒伐他汀0.8 mg/kg、1.6 mg/kg灌胃,同时持续高蛋氨酸饮食.12周后采血处死,检测各组小鼠血清 Hcy,血脂指标 TG、TC、HDL-C、LDL-C 水平,炎性指标 hsCRP、TNF-α、MMP-9和 AS 相关基因CXCL1、ICAM-1、VCAM-1表达情况.结果 高蛋氨酸组、叶酸组、低剂量组 Hcy均高于对照组,叶酸组、低剂量组和高剂量组均低于高蛋氨酸组,高剂量组又低于叶酸组(P＞0.05).高蛋氨酸组、叶酸组、低剂量组 TC 均高于对照组,低剂量组和高剂量组低于高蛋氨酸组,高剂量组低于叶酸组和低剂量组(P＞0.05);高蛋氨酸组 TG高于对照组,高剂量组低于高蛋氨酸组(P＞0.05);高蛋氨酸组、叶酸组、低剂量组 LDL-C 高于对照组,叶酸组、低剂量组和高剂量组低于高蛋氨酸组,高剂量组低于叶酸组和低剂量组(P＞0.05);高蛋氨酸组、叶酸组、低剂量组 HDL-C低于对照组,高剂量组高于高蛋氨酸组、叶酸组和低剂量组(P＞0.05).与对照组比较,高蛋氨酸组、叶酸组、瑞舒伐他汀低剂量组和高剂量组血清 hsCRP、TNF-α水平明显升高,MMP-9明显下降(P＞0.05);高剂量组各炎性指标均明显低于高蛋氨酸组、叶酸组及低剂量组(P＞0.05).叶酸组、瑞舒伐他汀低剂量组和高剂量组主动脉组织CXCL1、ICAM-1、VCAM-1、MMP-9阳性细胞百分比明显低于高蛋氨酸组(P＞0.05);与叶酸组、低剂量组比较,高剂量组各 AS相关基因阳性细胞百分比明显降低(P＞0.05);高蛋氨酸组、叶酸组、瑞舒伐他汀低剂量组和高剂量组主动脉组织CXCL1、ICAM-1、VCAM-1、MMP-9阳性细胞百分比明显高于对照组(P＞0.05);高剂量组 CXCL1、ICAM-1、VCAM-1、MMP-9阳性细胞百分比明显低于高蛋氨酸组、叶酸组和低剂量组(P＞0.05);各 AS相关基因阳性细胞百分比在叶酸组、低剂量组之间差异均无统计学意义(P＜0.05).结论 蛋氨酸过量摄入可诱发小鼠HHcy水平,而高剂量瑞舒伐他汀有助于降低 HHcy小鼠血清 Hcy水平,改善血脂紊乱,下调AS相关基因的表达.