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大麻素 2 型受体激动剂对肠缺血再灌注引起的功能衰竭和破坏炎症的治疗效果。

The curative effect of cannabinoid 2 receptor agonist on functional failure and disruptive inflammation caused by intestinal ischemia and reperfusion.

机构信息

Department of Medical Pharmacology, Medical Faculty, University of Duzce, Duzce, Turkey.

Department of Medical Pharmacology, Medical Faculty, University of Adiyaman, Adiyaman, Turkey.

出版信息

Fundam Clin Pharmacol. 2020 Feb;34(1):80-90. doi: 10.1111/fcp.12502. Epub 2019 Aug 28.

DOI:10.1111/fcp.12502
PMID:31373049
Abstract

Ischemia and reperfusion of intestinal tissue (intestinal I/R) induce disruption of ileal contractility and chain responses of inflammatory. The aim of this study was to reveal whether therapeutic value of cannabinoid 2 (CB2) receptor activity in the intestinal I/R, via to the exogenous administration of CB2 agonist (AM-1241). Intestinal I/R injury were performed through 30-min ischemia and 150-min reperfusion of mesenteric artery in Wistar rats. The pre-administered doses of 0.1, 1, and 5 mg/kg of CB2 agonist were studied to inhibit inflammation of intestinal I/R injury including ileum smooth muscle contractility, polymorphonuclear cell migration, oxidant/antioxidant defense system, and provocative cytokines. Pre-administration with CB2 receptor agonist ensured to consider improving the disrupted contractile responses in ileum smooth muscle along with decreased the formation of MDA that production of lipid peroxidation, reversed the depleted glutathione, inhibited the expression of TNF-α and of IL-1β in the intestinal I/R of rats. Taken together results of this research, the agonistic activity of CB2 receptor for healing of intestinal I/R injury is ensuring associated with anti-inflammatory mechanisms such as the inhibiting of migration of inflammatory polymorphonuclear cells that origin of acute and initial responses of inflammation, the inhibiting of production of provocative and pro-inflammatory cytokines like TNF-α and IL-1β, the rebalancing of oxidant/antioxidant redox system disrupted in injury of reperfusion period and the supporting of physiologic defensive systems in endothelial and inducible inflammatory cells.

摘要

肠组织的缺血再灌注(肠道 I/R)会导致回肠收缩性和炎症级联反应的破坏。本研究的目的是通过肠组织 I/R 中内源性大麻素 2(CB2)受体活性的治疗价值,即外源性给予 CB2 激动剂(AM-1241),来揭示其治疗价值。在 Wistar 大鼠的肠系膜动脉中进行 30 分钟的缺血和 150 分钟的再灌注,以建立肠道 I/R 损伤模型。研究了 0.1、1 和 5 mg/kg 三个剂量的 CB2 激动剂,以抑制肠道 I/R 损伤的炎症,包括回肠平滑肌收缩性、多形核细胞迁移、氧化应激/抗氧化防御系统和促炎细胞因子。CB2 受体激动剂的预先给药可以改善回肠平滑肌的收缩反应,减少丙二醛的形成,丙二醛是脂质过氧化的产物,逆转谷胱甘肽的耗竭,抑制 TNF-α和 IL-1β在肠道 I/R 中的表达。综上所述,本研究结果表明,CB2 受体的激动活性对肠道 I/R 损伤的治疗作用与抗炎机制有关,如抑制炎症性多形核细胞的迁移,这是炎症的急性和初始反应的来源,抑制促炎和致炎细胞因子如 TNF-α和 IL-1β的产生,重新平衡再灌注损伤期间破坏的氧化应激/抗氧化还原系统,并支持内皮细胞和诱导性炎症细胞的生理防御系统。

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