摘要
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氨基丙组10只[β氨基丙100mg/(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。
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. Ex- pression 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 ex- pression 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.
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2013年第6期628-631,共4页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
