摘要
目的探讨阿托伐他汀对异丙肾上腺素(ISO)诱导的慢性心力衰竭(CHF)大鼠左室重构和心功能的影响以及可能的机制。方法将ISO诱导的CHF大鼠随机分成ISO组与ISO+阿托伐他汀组,同时以正常大鼠为对照组。4周后行心动超声、血流动力学、血清细胞因子检查和心脏标本检测(左室质量／体质量)及RT-PCR 检测心肌基质金属蛋白酶-2(MMP-2)mRNA表达水平。结果 (1)与对照组比较,ISO组左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、左室舒张末压(LVEDP)及左室压力最大下降速率(dp／dtmin)明显升高,左室收缩末压(LVESP)、左室压力最大上升速率(dp／dtmax)及左室短轴缩短率(FS)则明显降低(P<0．01);而ISO+阿托伐他汀组,LVESD、LVEDD、LVEDP、dp／dtmin和LVESP、dp／dtmax及FS值则介于对照组与ISO组之间,且与ISO组比较, LVESD、LVEDD、LVEDP及dp／dtmin明显降低,而LVESP、dp／dtmax及FS则明显升高(P<0．05);左室后壁厚度在 ISO组和ISO+阿托伐他汀组没有明显的不同(P>0．05)。(2)与对照组相比,ISO组和ISO+阿托伐他汀组左室质量／体质量(LVW／BW)明显增大(P<0．01);但与ISO组比较,ISO+阿托伐他汀组LVW／BW降低(P<0．05)。 ISO组MMP-2 mRNA表达水平较对照组明显升高(P<0．01),而ISO+阿托伐他汀组较ISO组降低(P<0．05)。 (3)ISO组大鼠血清肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平均比正常对照组显著升高(P<0．01); 与ISO组比较,ISO+阿托伐他汀组血清TNF-α和IL-α水平明显降低(P<0．05)。结论阿托伐他汀通过降低ISO诱导的CHF大鼠细胞因子水平,从而改善左室重构及心脏功能。
Objective To investigate the effects of atorvastatin on left ventricular （LV） remodeling and dysfunction of rats with isoproterenol （ISO）-induced chronic heart failure and possible mechanisms, Methods We measured cardiac conformation ,contractile performance, serum cytokines levels and mRNA expression levels of matrix metalloproteinase-2 （MMP-2） in 15 age-matched normal adult rats and 11 rats with ISO-induced heart failure and 14 rats with ISO-induced heart failure but received atorvastatin treatment. Results （1）LV end diastolic diameter （LVEDD）, LV end systolic diameter（LVESD）, LV end diastolic pressure（LVEDP） and dp/dtmin in ISO group and ISO ＋ atorvastatin group were significantly larger and LV fractional shortening （FS）, LV end systolic pressure （LVESP） and dp/dtmax were significantly less than those of control group, respectively （P 〈 0.01 ）;in ISO ＋ atorvastatin group, LVEDD, LVESD, LVEDP and dp/dtmin were significantly less and FS, LVESP and dp/dtmax were significantly larger than ISO group （P 〈 0.05）;there was no significant difference of LV posterior wall thickness at end diastole between ISO group and ISO ＋ atorvastatin group（P 〉 0.05）. （2）The ratios of LV weight to body weight（LVW/BW）in ISO group and ISO ＋ atorvastatin group were significantly higher than that in control group （P 〈 0.01 ）,but LVW/BW in ISO ＋ atorvastatin group decreased when compared with ISO group （P 〈 0.05 ） ;mRNA expression of MMP-2 was significantly higher in ISO group than in control group （P 〈 0.01 ） ,while it decreased in ISO ＋ atorvastatin group when compared with ISO group （P 〈 0.05）. （3）The serum levels of TNF-α and IL-6 were significantly higher in ISO group than in control group （P 〈 0,01）,but the serum levels of TNF-α and IL-6 in ISO ＋ atorvastatin group decreased significantly when compared with ISO group （P 〈 0.05）. Conclusions Atorvastatin, administered as soon as possible when ISO induced myocardial necrosis occurs, can greatly improve left ventricular remodeling and dysfunction through decreasing the serum levels of TNF-α and IL-6.
出处
《中国地方病学杂志》
CAS
CSCD
北大核心
2006年第2期156-159,共4页
Chinese Jouranl of Endemiology
基金
黑龙江省自然科学基金资助项目(D2004-41)
