慢性间歇性低氧对心肌梗死急性期小鼠C1q肿瘤坏死因子相关蛋白9的表达及对心功能的影响

目的:评价慢性间歇性低氧(CIH)对心肌梗死急性期小鼠心肌组织中C1q肿瘤坏死因子相关蛋白9(CTRP9)的表达及心功能的影响。方法:将36只,雄性,C57BL/6野生型小鼠,随机分为常氧(NOR)组(n=18)和CIH组(n=18)。将CIH组小鼠放入氧气浓度在6%~21%之间循环的低氧舱内28 d,同时NOR组在常氧环境中饲养。28 d后两组小鼠均结扎左冠状动脉建立心肌梗死模型。于结扎后3 d(n=6)、7 d(n=6)和14 d(n=6)时利用多普勒超声评估小鼠左心室结构与功能,然后将其处死。在结扎后3 d、7d时分别用免疫印迹法及RT-PCR法检测心肌中CTRP9表达、ELISA法检测血浆中CTRP9浓度以及用MASSON染色比较各组心肌纤维化面积。结果:NOR组和CIH组小鼠在冠状动脉结扎后3、7及14 d时的左心室内径均逐渐增加(P<0.001),LVEF和缩短分数(FS)均逐渐降低(P<0.001)。在结扎后3 d时,与NOR组相比,CIH组小鼠心肌组织中CTRP9的表达和血浆中CTRP9浓度明显升高(P<0.05;P<0.01),纤维化面积明显减小(P<0.001),LVEF和FS显著高于NOR组(P<0.05)。结论:与NOR组相比,CIH干预可以使心肌梗死急性期小鼠的心肌组织中CTRP9的表达增加,心肌纤维化面积减小,心功能改善。CIH引起的缺氧预适应可能在心肌梗死急性期发挥保护作用。

Effects of chronic intermittent hypoxia on the expression of C1q tumor necrosis factor-related protein 9 and cardiac function in mice with acute myocardial infarction

Objective:To evaluate the impact of chronic intermittent hypoxia(CIH)on the expression of C1 q tumor necrosis factor-related protein 9(CTRP9)in the myocardial tissue and cardiac function in mice with acute myocardial infarction.Methods:36 male C57 BL/6 wild-type mice were randomly divided into normoxia(NOR)group(n=18)and CIH group(n=18).Mice in the CIH group were placed in a hypoxic chamber with an oxygen concentration between 6%and 21%for 28 days,while the NOR group was incubated in a normoxic environment.After 28 days,the left coronary artery was ligated in both groups to establish a model of myocardial infarction.Doppler ultrasound was used to assess the structure and function of the left ventricle(LV)at 3(n=6),7(n=6),and 14 days(n=6)after ligation.At 3 and 7 days after ligation,the expression of myocardial CTRP9 in myocardium was detected by western-blot and RT-PCR,the concentration of CTRP9 in plasma was detected by ELISA,and the area of myocardial fibrosis was compared by MASSON staining.Results:In the NOR and CIH groups,the left ventricular diameter increased gradually at 3,7,and 14 days after coronary artery ligation(both P<0.001),and LVEF and fractional shortening(FS)decreased(both P<0.001).At 3 days after ligation,compared with the NOR group,the expression of CTRP9 in myocardium and the concentration of CTRP9 in plasma in the CIH group were significantly increased(P<0.05 and P<0.01,respectively),and the area of fibrosis was significantly reduced(P<0.001).LVEF and FS in the CIH group were significantly higher than those in the NOR group(P<0.05).Conclusions:Compared with the NOR group,after CIH intervention,the expression of CTRP9 in myocardial tissue increased in the acute phase of myocardial infarction,the area of fibrosis deceased,and cardiac function was improved.CIH-hypoxia preconditioning may play an protective role in the acute phase of myocardial infarction.