Department of Physiology, Hebei Medical University, Shijiazhuang, 050017, China.
Department of Clinical Laboratory, Second Hospital, Hebei Medical University, Shijiazhuang, 050000, China.
J Physiol Sci. 2013 Jan;63(1):47-53. doi: 10.1007/s12576-012-0228-5. Epub 2012 Sep 25.
Anandamide (AEA), one of endocannabinoids, has been reported to exhibit a cardioprotective ability to limit the damage produced by ischemia-reperfusion injury. AEA reportedly enhanced heat shock protein 72 (HSP72) and HSP25 expression in lungs to protect against lung inflammation. This study tested the hypothesis that intravenously injected AEA would induce HSP72 in the heart and thus render cardioprotection against ischemia-reperfusion injury in rats. Cardiac expression of HSPs was quantitatively evaluated in rats by Western blot analysis. That intravenously injected AEA 1 mg/kg in vivo induced expression of HSP72, which peaked at 24 h after administration. The enhancement of HSP72 by AEA was blocked by cannabinoid 2 (CB(2)) receptor antagonist AM630, but not cannabinoid 1 (CB(1)) receptor antagonist AM251. Therefore, the rats were induced with a 30-min coronary occlusion followed by a 120-min reperfusion in vivo at 24 h after administration of drugs or vehicle, and then the infarct size was measured. AEA reduced myocardial infarct size compared to control group. Pretreatment with AM630 but not AM251 abolished the infarct size-limiting effect of AEA. Further study demonstrated pretreatment with phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin, Akt inhibitor MK-2206 and AM630 attenuated phosphorylation of Akt and AEA-induced HSP72 expression. The results suggest that AEA is cardioprotective against ischemia-reperfusion insult through its induction of HSP72, which might be mediated by the PI3K/Akt signaling pathway. These effects were mediated by CB(2) but not CB(1) receptors.
花生四烯酸乙醇胺（AEA），一种内源性大麻素，已被报道具有心脏保护作用，可以限制缺血再灌注损伤产生的损伤。AEA 据报道可增强肺部热休克蛋白 72（HSP72）和 HSP25 的表达，从而防止肺部炎症。本研究检验了这样一个假设，即静脉注射 AEA 会诱导心脏中的 HSP72，从而对大鼠的缺血再灌注损伤提供心脏保护作用。通过 Western blot 分析定量评估了 HSP 在大鼠心脏中的表达。结果显示，体内静脉注射 1mg/kg 的 AEA 诱导 HSP72 表达，在给药后 24 小时达到峰值。AEA 增强 HSP72 的作用被大麻素 2（CB2）受体拮抗剂 AM630 阻断，但被大麻素 1（CB1）受体拮抗剂 AM251 阻断。因此，在给药后 24 小时，大鼠在体内诱导 30 分钟冠状动脉闭塞，然后再灌注 120 分钟，然后测量梗塞面积。与对照组相比，AEA 减少了心肌梗塞面积。预先给予 AM630 但不给予 AM251 可消除 AEA 对梗塞面积的限制作用。进一步的研究表明，预先给予 PI3K 抑制剂渥曼青霉素、Akt 抑制剂 MK-2206 和 AM630 可减弱 Akt 的磷酸化和 AEA 诱导的 HSP72 表达。结果表明，AEA 通过诱导 HSP72 对缺血再灌注损伤具有心脏保护作用，这可能是通过 PI3K/Akt 信号通路介导的。这些作用是由 CB2 而不是 CB1 受体介导的。
