气管滴注大气细颗粒物对大鼠心脏的急性毒性及其机制研究

为探讨大气细颗粒物(PM2.5)对大鼠心脏的急性毒性及其机制,将28只健康雄性Wistar大鼠随机分为空白膜对照组、7.5mg·kg-1、15mg·kg-1和30mg·kg-1剂量组.细颗粒物采用一次性咽喉部气管滴注染毒,24h后处死动物.分别于染毒30min、1h和24h后测定大鼠心电图,采用间接免疫荧光化学方法测定大鼠心脏缝隙连接蛋白Cx43的分布,采用免疫印迹法(Western blot)测定连接蛋白Cx43的表达;光镜下观察心脏的组织病理学改变.结果发现,染毒30min后,各组大鼠心律失常发生率均高于基础测量时,染毒1h后对照组恢复正常心律,而颗粒物染毒组仍显示异常心律,与对照组相比,15mg·kg-1和30mg·kg-1剂量组大鼠心律失常发生频率显著增加(p<0.05),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,15mg·kg-1和30mg·kg-1剂量组大鼠心肌Cx43荧光强度显著降低(p<0.01);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,15mg·kg-1和30mg·kg-1剂量组Cx43蛋白水平分别为对照的57%和51%,与对照组相比,差异具有显著性(p<0.01);病理切片结果发现,对照组和各剂量均可见到心肌横纹,心肌排列正常,横纹清晰,未见明显心肌细胞萎缩、变性,亦未见炎细胞浸润.本次研究结果表明,大气PM2.5可引起健康Wistar大鼠心律异常的发生,心肌组织Cx43分布和表达的异常可能是其机制之一.

Acute Heart Toxicity in Rats Induced by PM2.5 Intratracheal Instillation and Its Mechanisms

To study the acute effects of PM2.5 on rat heart and its mechanisms,twenty-eight healthy male Wistar rats were divided into four groups randomly.PM2.5 was administered by single intratracheal instillation at the dose of 0(blank control),7.5mg·kg-1,15mg·kg-1 and 30mg·kg-1.ECGs were monitored at 30min,1h and 24h after PM2.5 instillation.The rats were sacrificed after 24h,Cx43 distribution and protein expression in rat cardiac tissue was detected and pathological analysis was done.Exposure to PM2.5 at all tested doses significantly worsened the arrhythmia at 30min and 60min after instillation compared with the control(p<0.05),the arrhythmia returned to basal level after PM2.5 treatment for 24h.Cx43 on cardiac intercalated disc significantly decreased at the dose of 15mg·kg-1 and 30mg·kg-(1p<0.01).Western blot showed that Cx43 protein expression in cardiac tissue significantly decreased at 24h at the treatment of PM2.5 with the dose of 15mg·kg-1 and 30mg·kg-1(p<0.01).No pathological changes were seen on the the cardiac tissue of rats.Thus this is the first in vivo study indicated that downregulation of the cardiac Cx43 in rats is likely involved in the early damage of PM2.5 exposure-induced cardiac toxicity in health Wistar rats,and which may be related with arrhythmia induced by PM2.5.