间歇低氧大鼠心室重塑与心肌细胞凋亡和Rho激酶表达的关系
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摘要
目的观察睡眠中间歇低氧状态下大鼠心室重塑、血液动力学异常与心肌细胞凋亡和Rho激酶表达的关系,探讨间歇低氧与心室重塑和心力衰竭之间关系的分子机制。方法 3组雄性Wistar大鼠,每组8只,给予适度限制饮食量的普通饮食和每天正常运动量游泳1h,分为常氧(A组)、间歇低氧(B组)、间歇低氧+法舒地尔(C组),60d后检测血液动力学指标、心室重量、体重、形态学检测(HE染色和凋亡细胞检测)和RT-PCR查Rho激酶m RNA表达。结果与A组比较,B组血液动力学指标恶化、心室肥厚指数增加、心肌细胞排列紊乱、凋亡明显及Rho激酶表达增加。与B组比较,C组血液动力学指标改善、心室肥厚指数减小、心肌细胞排列紊乱减轻、凋亡减少及Rho激酶表达降低。结论间歇低氧与心室重塑、心力衰竭发生、发展密切相关。细胞凋亡和炎症因子Rho激酶表达增加与之密切相关。
Objective To study the relationship between remodling, hemodynamics parameters with the apoptosis and the expression of Rho kinase in myocardial cells with sleep intermittent hypoxia, and therefore to explore the molecular mechanisms of between intermittent hypoxia and remodling and heart failure.Methods Male Wistar rats were divided into 3 groups: a normal oxygen group(A group, n=8, breathing 21% O2 for 8h per day, eating limit normal diet 20g/d foreach rat, swimming 1h in 6pm), an intermittent hypoxia group(B group, n=8,breathing 10% O2 and air alterd per90 sec for 8h per day, eating limit normal diet 20g/d for each rat, swimming 1h in 6pm) and a fasudil group(C group, n=8,breathing 10% O2 and air alterd per90 sec for 8h per day, eating limit normal diet 20g/d for each rat, swimming 1h in 6pm, 20mg·kg-1·d-1 fasudil Qd, i.h.)Sixty days later, hemodynamics parameters, left ventricular weight, weight, HE staining of myocardial cells, apoptosis and Rho kinase m RNA expression were measured respectively. Results The hemodynamics parameters were deteriorated,the index of left ventricular hypertrophy was increased, myocardial cells were arranged in disorder, the apoptosis was obvious and the expression of Rho kinase m RNA was increased in B group as compared with A group. The conditions in C group were improved significantly as compared with B group. Conclusion Intermittent hypoxia as dangerous factor was associated with the occurrence and development of remodling and heart failure. The activitions of apoptosis and inflammatory cytokine-- Rho kinase may be the key factors in remodling and heart failure under sleep intermittent hypoxia.
引文
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