急性高原低氧对于大鼠心功能及其心肌组织miR-144表达影响的研究

Effect of acute hypobaric hypoxia at high altitude on cardiac function and the expression of miR-144 in myocardium in rats

目的探讨急性高原低氧对于大鼠心功能及其心肌组织miR-144表达的影响。方法应用低压氧舱模拟构建高原低氧大鼠模型。将6周龄雄性SD大鼠分为高原低氧3、7、14、28 d实验组以及常压常氧对照组,每组12只大鼠。超声心动图检测大鼠心脏结构和功能。qRT-PCR检测各组大鼠心肌组织miR-144表达。结果超声心动图检查结果显示,高原低氧3 d和7 d组大鼠LVEF和FS均低于对照组。高原低氧14 d和28 d组大鼠LVEF和FS均高于对照组。高原低氧各组大鼠PV peak velocity和PV peak gradient数值均低于对照组。高原低氧各组大鼠左心室收缩末内径(LVIDS)和舒张末内径(LVIDD)均低于对照组。高原低氧3、7、28 d组大鼠心肌组织miR-144表达均高于对照组,高原低氧14 d组大鼠心肌组织中miR-144表达低于对照组。Spearman相关性分析提示,心肌组织miR-144表达丰度与左心室射血分数和短轴缩短率呈负相关。结论急性高原低氧可导致大鼠左心室结构和功能发生变化,左心室内径缩小,室壁增厚,左心室舒张功能下降。高原低氧1周内左心室收缩功能下降,1周后左心室收缩功能恢复正常。急性高原低氧可导致大鼠心肌组织miR-144表达升高。miR-144表达与心功能变化呈负相关,推测miR-144可能参与调控高原低氧导致的心脏结构和功能变化。

Objective This study investigated the effects of acute hypobaric hypoxia at high altitude on cardiac function and the expression of miR-144 in myocardium in rats. Methods Adult male Sprague-Dawley rats were randomly assigned to a normoxic group and four hypoxic groups( HH group). Rats in hypoxic groups were exposed to simulated hypobaric hypoxia chamber equivalent to 7 000 meters for different durations( 3,7,14 and 28 days). Subsequently,echocardiography was used to detect cardiac structure and function in rats. QRT-PCR was used to detect the expression of miR-144 in myocardium of rats. Results Compared with the normoxic group,both LVEF and FS decreased in HH3 and HH7 group,both LVEF and FS increased in HH14 and HH28 group. Both PV peak velocity and PV peak gradient in all hypoxic groups were lower than those in normoxic group. Both LVIDD and LVIDS in all hypoxic groups were shorter than those in normoxic group. The LVPWD were thicker in all hypoxic groups than that in normoxic group. The expression of miR-144 in myocardium in HH3,HH7 and HH28 group were higher than that in normoxic group. The expression of miR-144 in myocardium in HH14 group was lower slightly than that in normoxic group.Spearman correlation analysis showed that the expression of miR-144 was negatively correlated with left ventricular ejection fraction and short axis shortening rate. Conclusion Acute hypobaric hypoxia at high altitude can lead to changes of cardiac structure and function in rats. The left ventricular diameter decreased,the wall thickened,and the diastolic function decreased in rats by high altitude hypobaric hypoxia. Left ventricular systolic function increased during one week by high altitude hypobaric hypoxia,but recovered then. Acute hypobaric hypoxia at high altitude could increase the expression of miR-144 in myocardium. The expression of miR-144 in myocardium was negatively correlated with LVEF and FS. It was possible that miR-144 could regulate cardiac function at high altitude hypobaric hypoxia.