大气PM2.5对自发性高血压大鼠心律的影响及其机制研究

Effect of PM2.5 Intratracheal Instillation on Heart Rhythm in SHR Rats

目的探讨大气细颗粒物(PM2.5)对自发性高血压大鼠(SHR)心律的影响及其机制。方法将28只自发性高血压大鼠(SHR)随机分为4组,即空白膜对照组、7.5、15和30mg/kg剂量组。颗粒物采用一次性气管滴注染毒,染毒24h后处死动物。染毒30min、1h、24h后测定SHR大鼠心电图,采用间接免疫荧光细胞化学方法测定大鼠心脏缝隙连接蛋白Cx43的分布及表达密度,采用免疫印迹法测定连接蛋白Cx43的表达;采用试剂盒法测定心肌组织MDA和SOD水平。结果染毒30min后,各组SHR大鼠均较基础测量时心律失常发生率增加,染毒1h后对照组恢复正常心律,而染毒组仍显示异常心律,染毒24h后各组均恢复正常心律。Cx43免疫荧光结果显示,染毒24h后,15和30mg/kg剂量组SHR大鼠心肌连接蛋白Cx43荧光强度显著降低(P<0.01),其中30mg/kg剂量组心肌细胞闰盘处几乎未见荧光分布;Western blot测定结果显示,随着PM2.5染毒剂量的增加,心肌组织Cx43表达逐渐减少,尤其以15、30mg/kg剂量组蛋白水平降低最为显著(P<0.01),分别为对照的56%和45%;此外,随着PM2.5染毒剂量的增加,心肌组织丙二醛(MDA)含量有所增加,超氧化物歧化酶(SOD)活力逐渐减少,但与对照组相比,差异无统计学意义(P>0.05)。结论大气PM2.5可引起自发性高血压大鼠心律异常的发生,心肌组织Cx43表达的减少可能是其机制之一。

Objective To study the acute effects of PM2.5 on the heart rhythm of spontaneously hypertensive rats（SHR）and the mechanism. Methods Twenty-eight male spontaneously hypertensive rats （SHR）were randomly divided into four groups. PM2.5 was administered by intratracheal instillation at the doses of 0 mg/kg, 7.5 mg/kg, 15 mg/kg and 30 mg/kg respectively. ECGs were monitored at 30 min, 1 h and 24 h later. Results The numbers of the rats with arrhythmia in all groups increased at 30 min after treatment. At 1 h after treatment, in control group the rats recovered, but in PM2.5 groups abnormal ECGs was still showed. However, ECGs of all groups became normal 24 h later. As shown by laser scanning confocal microscope （LSCM）, the expression of Cx43 in the heart tissue of rats in 15 mg/kg and 30 mg/kg groups significantly decreased compared with the control group. There was no significant change in content of MDA and SOD in the heart tissue of PM2.5 treated rats. Conclusion PM2.5 exposure through inhalation may induce arrhythmia in SHR rats and the downregulated expression of Cx43 may play an important role in the pathogenesis.