大麻素受体1拮抗剂genistein减轻了大麻引起的血管炎症

流行病学研究显示,大麻会增加心血管疾病(CVD)的风险;然而,对其机制所知甚少。大麻的精神活性成分Δ9-四氢大麻酚(Δ9-THC)与血管中的大麻素受体1(CB1/CNR1)结合,与心血管疾病有关。英国生物银行的一项分析发现,大麻是心血管疾病的一个危险因素。我们发现,吸食大麻会激活与心血管疾病有关的炎症细胞因子。在硅学虚拟筛选中,发现大豆异黄酮genistein是一种推定的CB1拮抗剂。人诱导的多能干细胞衍生的内皮细胞被用来模拟Δ9-THC通过NF-κB信号诱导的炎症和氧化压力。用siRNA、CRISPR干扰和genistein对CB1受体进行敲除,削弱了Δ9-THC的影响。在小鼠中,染料酶阻断了Δ9-THC诱导的线状肌内皮功能障碍,减少了动脉粥样硬化斑块,并且对中枢神经系统的渗透性最小。染料木素是一种CB1拮抗剂,可减弱Δ9-THC引起的动脉粥样硬化。

Cannabinoid receptor 1 antagonist genistein attenuates marijuana-induced vascular inflammation

大麻素受体1拮抗剂genistein减轻了大麻引起的血管炎症
Epidemiological studies reveal that marijuana increases the risk of cardiovascular disease (CVD); however, little is known about the mechanism. Δ9-tetrahydrocannabinol (Δ9-THC), the psychoactive component of marijuana, binds to cannabinoid receptor 1 (CB1/CNR1) in the vasculature and is implicated in CVD. A UK Biobank analysis found that cannabis was an risk factor for CVD. We found that marijuana smoking activated inflammatory cytokines implicated in CVD. In silico virtual screening identified genistein, a soybean isoflavone, as a putative CB1 antagonist. Human-induced pluripotent stem cell-derived endothelial cells were used to model Δ9-THC-induced inflammation and oxidative stress via NF-κB signaling. Knockdown of the CB1 receptor with siRNA, CRISPR interference, and genistein attenuated the effects of Δ9-THC. In mice, genistein blocked Δ9-THC-induced endothelial dysfunction in wire myograph, reduced atherosclerotic plaque, and had minimal penetration of the central nervous system. Genistein is a CB1 antagonist that attenuates Δ9-THC-induced atherosclerosis.

如若转载,请注明出处:https://www.ouq.net/%e5%a4%a7%e9%ba%bb%e7%b4%a0%e5%8f%97%e4%bd%931%e6%8b%ae%e6%8a%97%e5%89%82genistein%e5%87%8f%e8%bd%bb%e4%ba%86%e5%a4%a7%e9%ba%bb%e5%bc%95%e8%b5%b7%e7%9a%84%e8%a1%80%e7%ae%a1%e7%82%8e%e7%97%87.html

(0)
打赏 微信打赏,为服务器增加100M流量 微信打赏,为服务器增加100M流量 支付宝打赏,为服务器增加100M流量 支付宝打赏,为服务器增加100M流量
上一篇 2022年4月30日 上午1:15
下一篇 6天前

相关推荐