肥厚型心肌病相关代谢基因NCX1对大气混合污染物处理的表达响应

Response of hypertrophic cardiomyopathy-associated metabolic gene NCX1 to airborne pollutants

目的检测NCX1基因在大气混合污染物处理下的高血压大鼠(spontaneously hypertensive rats,SHR)心肌中的表达情况,探讨大气混合污染物对肥厚型心肌病的分子影响机制。方法选取80只SHR大鼠随机分为对照组及低、中、高剂量组,分别以1 d、7 d、30 d、60 d、90 d五个时间点进行检测。大鼠染尘每周1次,染毒每天连续进行3.5 h;对照组气管灌注生理盐水,正常呼吸。建模完成后,杀鼠取近左心室处心肌组织提取总RNA,利用实时荧光定量PCR检测NCX1基因表达量。结果 SHR大鼠低中高剂量组中NCX1基因在不同时间段均为高表达,差异有统计学意义(P<0.05)。随着处理剂量的增高,NCX1基因相对表达量发生明显变化的时间提前。结论大气混合污染物可能是通过使NCX1基因表达上调,增加胞内钙离子的浓度,使心肌收缩功能发生改变,进而参与肥厚型心肌病的发生与发展。

Objective To detect the expression of NCX1 gene in myocardium of spontaneously hypertensive rats（SHR） treated with atmospheric mixed contaminants and to explore the molecular mechanism of atmospheric mixed contami- nants on hypertrophic cardiomyopathy. Methods Eighty SHR rats were randomly divided into control group, low, mid- dle and high dose groups, and were detected at five time points： 1 d, 7 d, 30 d, 60 d, and 90 d. Rats were exposed to dust once a week for 3.5 hours per day. Controls were given tracheal infusion of normal saline and normal breathing. After the modeling was completed, the total RNA extracted from the left ventricle was extracted from the left ventricle and the expression of NCX1 gene was detected by real-time fluorescence quantitative PCR. Results The expression of NCX1 gene in the low, medium, high dose SHR group was significantly higher than that in the control group（P〈O.05）. With the increase of treatment dose, the time for significant changes in the relative expression of NCX1 gene was advanced. Conclusion The airborne mixed pollutants may be involved in the occurrence and development of hypertrophic car- diomyopathy by up-regulating the expression of NCX1 gene, increasing the concentration of intracellular calcium and increasing the contractile function of the heart muscle.