Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury
Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury
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DOI：
10.1152/ajpheart.00098.2007
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发表时间：
2007-12-01
影响因子：
4.8
通讯作者：
Lotan, Chaim
中科院分区：
文献类型：
--
作者：
Durst, Ronen;Danenberg, Haim;Lotan, Chaim
大麻二酚（CBD）是一种主要的非精神活性大麻成分，具有通过增强腺苷信号传导介导的抗炎活性。由于腺苷受体是缺血性心脏病的有前途的药物靶点，我们测试了CBD对缺血大鼠心脏的影响。对于体内研究，将左前降支冠状动脉短暂结扎30分钟，并用CBD（5 mg/kg ip）或载体处理大鼠7天。超声心动图检查心功能。进行形态计量学和组织学检查。对于离体评价，在动物被杀死之前24和1小时施用CBD，并且收获心脏用于生理测量。体内研究显示，CBD处理的动物中的缩短分数得以保留：CBD处理的大鼠和对照大鼠中分别从48 +/- 8至39 +/- 8%和从44 +/- 5至32 +/- 9%（n = 14，P < 0.05）。CBD处理的动物中的肉芽组织大小减少了66%，尽管定性评估的风险区域几乎相同（CBD和对照组分别为9.6 +/- 3.9和28.2 +/- 7.0%，P < 0.001）和肉芽组织比例。CBD处理的动物中的心肌炎与心肌炎症减少和IL-6水平降低相关（CBD和对照大鼠中分别为254 +/-22和2，812 +/-500 pg/ml，P < 0.01）。在离体心脏中，CBD处理的心脏和对照心脏之间的梗死面积、缺血和再灌注期间左心室发展压力或冠状动脉流量没有显著差异。我们的研究表明，CBD在体内诱导了对缺血的实质性心脏保护作用，而在体外并未观察到这种作用。由于CBD以前曾被用于人类而不会引起副作用，因此它可能是一种有前途的心肌缺血新疗法。
Cannabidiol (CBD) is a major, nonpsychoactive Cannabis constituent with anti-inflammatory activity mediated by enhancing adenosine signaling. Inasmuch as adenosine receptors are promising pharmaceutical targets for ischemic heart diseases, we tested the effect of CBD on ischemic rat hearts. For the in vivo studies, the left anterior descending coronary artery was transiently ligated for 30 min, and the rats were treated for 7 days with CBD (5 mg/kg ip) or vehicle. Cardiac function was studied by echocardiography. Infarcts were examined morphometrically and histologically. For ex vivo evaluation, CBD was administered 24 and 1 h before the animals were killed, and hearts were harvested for physiological measurements. In vivo studies showed preservation of shortening fraction in CBD-treated animals: from 48 +/- 8 to 39 +/- 8% and from 44 +/- 5 to 32 +/- 9% in CBD-treated and control rats, respectively (n = 14, P < 0.05). Infarct size was reduced by 66% in CBD-treated animals, despite nearly identical areas at risk (9.6 +/- 3.9 and 28.2 +/- 7.0% in CBD and controls, respectively, P < 0.001) and granulation tissue proportion as assessed qualitatively. Infarcts in CBD-treated animals were associated with reduced myocardial inflammation and reduced IL-6 levels (254 +/- 22 and 2,812 +/- 500 pg/ml in CBD and control rats, respectively, P < 0.01). In isolated hearts, no significant difference in infarct size, left ventricular developed pressures during ischemia and reperfusion, or coronary flow could be detected between CBD-treated and control hearts. Our study shows that CBD induces a substantial in vivo cardioprotective effect from ischemia that is not observed ex vivo. Inasmuch as CBD has previously been administered to humans without causing side effects, it may represent a promising novel treatment for myocardial ischemia.