激动M3-mAchR对乌头碱诱发大鼠心律失常的保护机制的研究  

The protective mechanism via activation of M3 receptor in aconitine-induced arrhythmias in rats

作　　者：乔尚[1] 尚佳[1] 董巧玲[1] 郭曙军[1] 

机构地区：[1]巴彦淖尔市医院心内科,内蒙古巴彦淖尔015000

出　　处：《临床和实验医学杂志》2017年第24期2408-2411,共4页Journal of Clinical and Experimental Medicine

摘　　要：目的通过乌头碱诱导的大鼠心律失常模型,研究匹罗卡品对心律失常的可能保护机制。方法 32只Wistar大鼠,雌雄不限,随机分成4组:模型组、4-二甲基氨基吡啶(4-DAMP)组、匹罗卡品组、匹罗卡品+4-DAMP组。4-DAMP组和匹罗卡品组大鼠,在股静脉静注乌头碱之前,分别提前5 min静注4-DAMP(0.12μg/kg)和匹罗卡品(0.2 mg/kg)。匹罗卡品+4-DAMP组大鼠,先给与M3-mAChR拮抗剂4-DAMP,5 min之后再给与匹罗卡品,再5min之后,用灌流泵经大鼠股静脉灌输乌头碱(0.06μg/min)诱发心律失常。观察每组大鼠的心律失常的严重程度,直至实验大鼠死亡。比较四组大鼠心律失常发生的起始时间、心肌室速和室颤发生时程、Mest评分和存活时间。采用激光共聚焦显微镜观察分离的心肌细胞内钙浓度变化。结果与模型组比较,匹罗卡品显著延迟大鼠心律失常发生的起始时间(P<0.001),减少大鼠心肌室速发生时程(P<0.001)和室颤的发生时程(P<0.001),降低心律失常的严重性和Mest评分(P<0.001),增加大鼠的存活时间(P<0.001)。预先给与匹罗卡品能够显著降低乌头碱诱导的心肌细胞发生的钙浓度的增加(P<0.05),与匹罗卡品组比较M3-mAchR选择性拮抗剂4-DAMP能部分阻断匹罗卡品对心律失常的保护作用(P<0.001),但4-DAMP本身对乌头碱诱导的心律失常并没有保护作用(P>0.05)。结论匹罗卡品对乌头碱诱导的大鼠心律失常具有保护作用,这种作用可能是通过激活M3-mAChR产生的,其机制可能与Ca^(2+)有关。Objective To explore the underlying protective mechanism of pilocarpine by using aconitine-induced rat arrhythmia models.Methods Total 32 rats of either sex were randomly divided into 4 groups： model group,4-DAMP,pilocarpine,pilocarpine ＋ 4-DAMP. Pilocarpine（ 0. 2 mg/kg,intravenous） or 4-DAMP（ 0. 12 mg/kg,intravenous） were administrated 5 minutes before aconitine respectively. For pilocarpine ＋ 4-DAMP group,4-DAMP（ 0. 12 mg/kg,intravenous）,M3-mAChR antagonist was administrated 5 minutes before pilocarpine to verify the effect of M3-mAChR,then aconitine was injected via the femoral vein catheter with micro-infusion pump at a velocity of 0. 06 mg/min to induce ventricular arrhythmias. In each group,the arrhythmic severity was observed until the death of tested rats. Confocal microscopy was used to measure intracellular free-calcium concentrations（ [Ca2＋]i） in isolated myocytes. Results Compared with the model group,pilocarpine significantly delayed onset of arrhythmias（ P 〈 0. 001）,decreased the time course of ventricular tachycardia（ P 〈 0. 001） and fibrillation（ P〈 0. 001）,reduced arrhythmia score（ P 〈 0. 001）,and increased the survival time of arrhythmic rats（ P 〈 0. 001）. [Ca2＋]i overload induced by aconitine was reduced in isolated myocytes pretreated with pilocarpine（ P 〈 0. 05）. Compared with the pilocarpine group,M3-muscarinic acetylcholine receptor（ mAChR） antagonist 4-DAMP partially abolished the beneficial effects of pilocarpine（ P 〈 0. 001）,while 4-DAMP played no protection role in aconitine-induced rat arrhythmia. Conclusion Pilocarpine produced antiarrhythmic actions on arrhythmic rat induced by aconitine via stimulating the cardiac M3-mAChR. The mechanism may be related to the improvement of Ca2＋ handling.

关 键 词：大鼠 心律失常 匹罗卡品 M3受体 M3受体拮抗剂 心肌保护 

分 类 号：R965[医药卫生—药理学]