胰岛素抵抗对心室重构的影响及瑞舒伐他汀的干预作用  

Influence of insulin resistance on ventricular remodeling and intervention effect of rosuvastatin

作　　者：许伟源[1] 郑良荣[1] 郭航远[2] 彭放[2] 吕海涛[3] 

机构地区：[1]浙江大学医学院附属第一医院心内科,杭州310003 [2]绍兴市人民医院心内科,绍兴312000 [3]温州医学院研究生院,温州325035

出　　处：《上海交通大学学报（医学版）》2012年第10期1316-1320,共5页Journal of Shanghai Jiao tong University:Medical Science

摘　　要：目的探讨胰岛素抵抗对心室重构的影响,观察瑞舒伐他汀的干预效果并阐述其可能机制。方法取6周龄C57BL/6遗传背景的雄性LDLR-/-小鼠40只,随机分为4组,每组10只。对照组(NC组):标准饲料喂养;高脂高糖组(HFF组):标准饲料+21.1%脂肪+20%果糖喂养;瑞舒伐他汀干预组(HFFR组):在HFF组基础上加瑞舒伐他汀干预;甲羟戊酸内酯干预组(HFFRMA组):在HFFR组基础上加甲羟戊酸内酯喂养。分组干预12周后处死小鼠。采用氧电极法检测空腹血糖(FBS),ELISA法检测空腹血浆胰岛素水平(FINS),计算稳态模型的胰岛素抵抗指数(HOMA-IR)和左心室质量指数(LVWI),天狼猩红染色后计算心肌组织胶原容积分数(CVF),Western blotting法检测心肌组织中PPARα、MMP-9蛋白的表达。结果与NC组相比,其他三组的FBS、FINS、HOMA-IR、LVWI、CVF及PPARα、MMP-9蛋白的表达均明显升高,差异有统计学意义(P<0.05);经瑞舒伐他汀干预后,HFFR组和HFFRMA组的FBS、FINS、HOMA-IR均得到明显改善,LVWI、CVF及PPARα、MMP-9蛋白的表达均明显降低,与HFF组比较差异有统计学意义(P<0.05);但在HFFR组和HFFRMA组之间上述指标比较差异均无统计学意义(P>0.05)。结论高脂高糖饲料喂养12周后,可诱导LDLR-/-小鼠产生胰岛素抵抗;胰岛素抵抗可促使心肌纤维化,导致心室重构。瑞舒伐他汀可抑制心室重构,改善胰岛素抵抗,其机制可能与下调PPARα和MMP-9蛋白的表达有关,且此作用独立于降脂作用之外。Objective To investigate the influence of insulin resistance on the ventricular remodeling,and to observe the intervention effect of rosuvastatin and explore its possible mechanism.Methods Forty male LDLR-/-mice aged 6 weeks were randomized into control group（NC group,fed with normal diet）,high fat and high fructose diet group（HFF group,fed with normal diet＋21.1% fat＋20% fructose）,rosuvastatin intervention group（HFFR group,intervention with rosuvastatin on the basis of that in HFF group） and rosuvastatin and mevalonic acid intervention group（HFFRMA group,fed with mevalonic acid on the basis of that in HFFR group）,with 10 mice in each group.Mice were sacrificed 12 weeks after treatment,the fasting blood sugar（FBS） was determined by oxygen electrode method,fasting plasma insulin（FINS） was detected by ELISA,homeostasis model insulin resistance index（HOMA-IR） and left ventricular weight index（LVWI） were calculated,collagen volume fraction（CVF） of myocardial tissues was calculated with Picric-Sirius Red staining,and the expression of PPARα and MMP-9 protein in myocardial tissues was detected by Western blotting.Results FBS,FINS,HOMA-IR,LVWI,CVF and the expression of PPARα and MMP-9 protein in HFF group,HFFR group and HFFRMA group were significantly higher than those in NC group（P0.05）.After treatment with rosuvastatin,FBS,FINS and HOMA-IR in HFFR group and HFFRMA group were significantly improved,and LVWI,CVF and the expression of PPARα and MMP-9 protein in HFFR group and HFFRMA group were significantly lower than those in HFF group（P0.05）.However,there was no significant difference in these parameters between HFFR group and HFFRMA group（P0.05）.ConclusionInsulin resistance can be induced in LDLR-/-mice 12 weeks after high fat and high fructose diet.Insulin resistance may contribute to myocardial fibrosis and ventricular remodeling.Rosuvastatin can inhibit ventricular remodeling and improve insulin resistance,and the mechanism may be associated with the down-regula

关 键 词：胰岛素抵抗 心室重构 瑞舒伐他汀 

分 类 号：R96[医药卫生—药理学]