探讨慢性间歇性缺氧对小鼠心脏功能影响的机制研究

Effect of Chronic Intermittent Hypoxia on Cardiac Function in Mice

目的探讨慢性间歇性缺氧对小鼠心脏收缩功能影响的机制。方法野生型雄性小鼠(C57)20只,随机分成对照组,慢性间歇性缺氧组,每组10只。慢性间歇性缺氧组小鼠予间歇缺氧环境中(30s 8%O_2+30s 21%O_2)。4周后处死小鼠。分别通过心脏多普勒超声及单个心肌细胞分离检测心脏收缩功能;透视电镜检测超微结构改变;ATP萤火荧光素酶检测试剂盒测定ATP含量;Western blot法检测Akt、Bax、bcl-2及caspase-3水平的表达。结果与对照组相比慢性间歇性缺氧组小鼠出现明显心脏收缩功能(EF)减退(p<0.05)。慢性间歇性缺氧组小鼠与对照组相比ATP合成含量显著减少(p<0.05)。慢性间歇性缺氧组小鼠出现线粒体部分形态改变及线粒体嵴的断裂、缺失及有所减少(p>0.05,未达到统计学差异)。慢性间歇性缺氧组小鼠与对照组相比Akt表达水平显著下调(p<0.05),Bax/bcl-2显著增加(p<0.05),c-caspase-3水平表达显著上调(p<0.05)。结论慢性间歇性缺氧可显著降低小鼠心脏收缩功能、降低ATP的合成及导致细胞凋亡。

Objective To investigate the effects of chronic intermittent hypoxia on cardiac systolic function in mice. Methods 20 Wide-Type male mice were divided into two groups： normoxia group and intermittent hypoxia（30s 8% O2＋30s 21%O2） group. After four weeks, relative indicators were detected. Cardiac systolic function was assessed by echocardiography and threshold potential stimulation. The mitochondrial morphology was examined by electron microscope. ATP level was tested by Luciferase Reporter ATP Assay Kit. The expression level of Akt, Bax, bcl-2 and caspase-3were analyzed by Western blot. Results The systolic function of CIH group was decreased compared with that of normoxia group（p〈0.05）. ATP level was significantly decreased in CIH group（p〈0.05）. Morphological changes of mitochondria and mitochondrial rupture can be found in CIH group（p〈0.05）. The expression of Akt was significantly decreased and that of Bax/bcl-2 and c-caspase-3 was increased（all p〈0.05）. Conclusion Chronic intermittent hypoxia can significantly impair cardiac systolic function, reduce ATP synthesis, and aggravate cardiomyocyte apoptosis.