School of Pharmacy & Life Sciences, Institute for Health & Welfare Research, Robert Gordon University, Schoolhill, Aberdeen, UK.
Br J Pharmacol. 2010 Jul;160(5):1234-42. doi: 10.1111/j.1476-5381.2010.00755.x.
Cannabidiol (CBD) is a phytocannabinoid, with anti-apoptotic, anti-inflammatory and antioxidant effects and has recently been shown to exert a tissue sparing effect during chronic myocardial ischaemia and reperfusion (I/R). However, it is not known whether CBD is cardioprotective in the acute phase of I/R injury and the present studies tested this hypothesis.
Male Sprague-Dawley rats received either vehicle or CBD (10 or 50 microg kg(-1) i.v.) 10 min before 30 min coronary artery occlusion or CBD (50 microg kg(-1) i.v.) 10 min before reperfusion (2 h). The appearance of ventricular arrhythmias during the ischaemic and immediate post-reperfusion periods were recorded and the hearts excised for infarct size determination and assessment of mast cell degranulation. Arterial blood was withdrawn at the end of the reperfusion period to assess platelet aggregation in response to collagen.
CBD reduced both the total number of ischaemia-induced arrhythmias and infarct size when administered prior to ischaemia, an effect that was dose-dependent. Infarct size was also reduced when CBD was given prior to reperfusion. CBD (50 microg kg(-1) i.v.) given prior to ischaemia, but not at reperfusion, attenuated collagen-induced platelet aggregation compared with control, but had no effect on ischaemia-induced mast cell degranulation.
This study demonstrates that CBD is cardioprotective in the acute phase of I/R by both reducing ventricular arrhythmias and attenuating infarct size. The anti-arrhythmic effect, but not the tissue sparing effect, may be mediated through an inhibitory effect on platelet activation.
大麻二酚(CBD)是一种植物源大麻素,具有抗细胞凋亡、抗炎和抗氧化作用,最近已证明其在慢性心肌缺血再灌注(I/R)期间具有组织保护作用。然而,CBD 是否在 I/R 损伤的急性期具有心脏保护作用尚不清楚,本研究对此假说进行了检验。
雄性 Sprague-Dawley 大鼠在 30 分钟冠状动脉闭塞前 10 分钟或再灌注前 10 分钟(2 小时)给予载体或 CBD(10 或 50μgkg^-1^静脉注射)。记录缺血和再灌注后即刻期间室性心律失常的出现情况,并取出心脏进行梗死面积测定和肥大细胞脱颗粒评估。在再灌注期末抽取动脉血,以评估胶原诱导的血小板聚集。
CBD 在缺血前给药可减少缺血引起的心律失常总数和梗死面积,这种作用呈剂量依赖性。再灌注前给予 CBD 也可减少梗死面积。与对照组相比,CBD(50μgkg^-1^静脉注射)在缺血前给药而不是再灌注时给药可减轻胶原诱导的血小板聚集,但对缺血引起的肥大细胞脱颗粒无影响。
本研究表明,CBD 在 I/R 的急性期具有心脏保护作用,可减少室性心律失常并减轻梗死面积。抗心律失常作用,而不是组织保护作用,可能通过抑制血小板激活来介导。