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大麻素受体1拮抗剂AM251对失血性休克大鼠血管反应性的影响

Effects of cannabinoid receptor 1 antagonist AM251 on vasoreactivity in hemorrhagic shock rats
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摘要 目的拟观察大麻素受体1(CB1R)在失血性休克大鼠腹主动脉和肠系膜上动脉的表达变化情况,及大麻素CB1受体拮抗剂AM251对血管反应性的影响。方法将SD大鼠随机分为假手术(Sham)组和失血性休克(HS)组。检测休克动物血管反应性的变化,以及动脉血管大麻素CB1受体mRNA和蛋白表达情况;观察CB1受体拮抗剂AM251对休克后血管低反应性及低血压的影响。结果 HS组动物均发生血管低反应性,腹主动脉和肠系膜上动脉2~3级分支动脉血管组织CB1受体mRNA和蛋白均呈阳性表达;CB1受体拮抗剂AM251能显著提高休克后血管低反应性,并可明显改善休克后的低血压。结论大麻素CB1受体与大鼠失血性休克后血管低反应性密切相关,其拮抗剂具有抗重度失血性休克作用。 【Objective】To examine whether CB1 cannabinoid receptor(CB1R) was involved in the development of vascular hyporeactivity suffering from hemorrhagic shock,and the effects of CB1 receptor antagonist AM251 on this hemorrhagic shock was also studied.【Methods】We randomly assigned the SD rats to two groups: sham-operated(Sham) and hemorrhagic shock(HS) groups.Vascular reactivity was determined by observing the responses of mean arterial blood pressure(MAP) to intravenously injected norepinephrine.Then the changes of CB1R mRNA and protein in aorta and superior mesenteric artery(SMA) were detected by RT-PCR and Western blotting.In addition,we investigated the effects of CB1R antagonist on the vascular reactivity in rats with hemorrhagic shock.【Results】 In the animals from the HS group,vascular hyporeactivity was developed,and the expression levels of CB1R mRNA and protein in aorta and 2~3 branches of SMA were increased markedly.We further showed that CB1R antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-e-3-carboxamide(AM251),improved the vascular hyporeactivity,and significantly increased the arterial blood pressure in rats suffering from hemorrhagic shock.【Conclusion】CB1R is involved in the vascular hyporeactivity resulting from hemorrhagic shock in rats,and CB1R antagonist may be helpful for the patients with severe hemorrhagic shock.
出处 《中国现代医学杂志》 CAS CSCD 北大核心 2012年第30期9-13,共5页 China Journal of Modern Medicine
关键词 失血性休克 血管低反应性 大麻素CB1受体 hemorrhagic shock vascular hyporeactivity CB1 cannabinoid receptor
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