阿托伐他汀对慢性心力衰竭小鼠心肌组织赖氨酰氧化酶表达的影响

摘要

Objective To study the effect of atorvastatin on expression of lysyl oxidase (LOX) in myocardial tissue of mice with chronic heart failure (CHF) and its mechanism.Methods A CHF model of C57BL/6 mice was reproduced.Forty C57BL/6 mice were randomly divided into CHF group (n =10),atorvastatin treatment group [(n =11,gastric lavage in atorvastatin 3 mg/(kg · d)],β-aminopropionitrile treatment group [(n =10,gastric lavage in β-aminopropionitrile 100 mg/(kg · d)],and control group (n=9).The animals were killed at the end of week 4.Expression levels of LOX,MMP-9,NF-κB mRNA,phosphorated P38 and P38 protein in myocardial tissue of CHF mice were measured by RT-PCR and Western blot,respectively.Results The expression levels of LOX,NF-κB and MMP-9 mRNA were significantly higher in CHF group than in control group (P＜0.01) and significantly lower in atorvastatin treatment group than in CHF group (P＜0.01).The expression levels of LOX and phosphorated p38 were significantly higher in CHF group than in control group (P＜0.01) and significantly lower in atorvastatin treatment group and β-aminopropionitrile treatment group than in CHF group (P＜0.01).Conclusion Atorvastatin can down-regulate the expression of LOX in myocardial tissue of CHF mice and LOX inhibits cardiac remodeling by regulating the MMP-9 expression in myocardial tissue of CHF mice,which may be the important mechanism in delaying the progress of CHF.%目的 研究阿托伐他汀对慢性心力衰竭(CHF)小鼠心肌组织赖氨酰氧化酶(LOX)表达的影响及机制.方法 选取C57BL/6小鼠复制CHF小鼠模型,再随机分为CHF组10只、阿托伐他汀组11只[阿托伐他汀3 mg/(kg·d)灌胃]和β氨基丙腈组10只[β氨基丙w100 mg/(kg·d)灌胃].另设对照组9只.在4周末将小鼠处死,提取心肌组织RNA及蛋白质,RT-PCR法测定心肌组织LOX、基质金属蛋白酶9(MMP-9)及NF-κB的mRNA表达水平,Western blot测定心肌组织LOX、磷酸化p38及p38蛋白表达水平.结果 CHF组小鼠心肌组织LOX、MMP-9、NF-κB mRNA表达明显高于对照组(P＜0.01)；阿托伐他汀组心肌组织LOX、MMP-9、NF-κB mRNA表达较CHF组明显下调(P＜0.01).CHF组心肌组织LOX及磷酸化p38蛋白表达明显高于对照组(P＜0.01)；与CHF组比较,阿托伐他汀组及β氨基丙g组心肌组织LOX及磷酸化p38蛋白表达明显下降(P＜0.01).结论 阿托伐他汀可逆转CHF小鼠心肌组织LOX的表达,LOX可通过调节CHF小鼠心肌组织MMP-9表达,从而抑制心脏重构,这可能是延缓CHF进展的重要机制.