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大麻素受体 2 激动剂对盲肠结扎穿刺诱导的脓毒症大鼠脑、肺、肝和心脏损伤的改善作用。

The ameliorating effect of cannabinoid type 2 receptor activation on brain, lung, liver and heart damage in cecal ligation and puncture-induced sepsis model in rats.

机构信息

Department of Physiology, Faculty of Medicine, Yozgat Bozok University, Yozgat, Turkey.

Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey.

出版信息

Int Immunopharmacol. 2020 Jan;78:105978. doi: 10.1016/j.intimp.2019.105978. Epub 2019 Nov 22.

Abstract

Uncontrolled infection and increased inflammatory mediators might cause systemic inflammatory response. It is already known that Cannabinoid Type 2 (CB2) receptors, which are commonly expressed in immune cells and in many other tissues, have an effect on the regulation of immune response. In the present study of ours, the effects of CB2 receptor agonist JWH-133 was investigated on cecal ligation and puncture (CLP)-induced polymicrobial sepsis model in rats. In the present study, Sprague-Dawley rats were divided into 5 groups (i.e. the Sham, CLP, JWH-133 0.2 mg/kg, JWH-133 1 mg/kg, and JWH-133 5 mg/kg Groups). Except for the Sham Group, the CLP-induced sepsis model was applied to all groups. The histopathological damage in brain, lung, liver and, heart was examined and the caspase-3, p-NF-κB, TNF-α, IL-1β and IL-6 levels were determined immunohistochemically. The serum TNF-α, IL-1β, IL-6, IL-10 levels were examined with the ELISA Method. The JWH-133 treatment decreased the histopathological damage in brain, heart, lung, and liver and reduced the caspase-3, p-NF-κB, TNF-α, IL-1β, IL-6 levels in these tissues. In addition to this, JWH-133 treatment also decreased the serum TNF-α, IL-1β, IL-6 levels, which were increased due to CLP, and increased the anti-inflammatory cytokine IL-10 levels. In the present study, it was determined that the CB2 receptor agonist JWH-133 decreases the CLP-induced inflammation, and reduces the damage in brain, lung, liver and heart. Our findings show the therapeutic potential of the activation of CB2 receptors with JWH-133 in sepsis.

摘要

未控制的感染和增加的炎症介质可能会引起全身炎症反应。已经知道,大麻素受体 2(CB2)受体,通常在免疫细胞和许多其他组织中表达,对免疫反应的调节有影响。在我们目前的研究中,研究了 CB2 受体激动剂 JWH-133 对大鼠盲肠结扎和穿刺(CLP)诱导的多微生物脓毒症模型的影响。在本研究中,将 Sprague-Dawley 大鼠分为 5 组(即假手术组、CLP 组、JWH-1330.2mg/kg 组、JWH-1331mg/kg 组和 JWH-1335mg/kg 组)。除假手术组外,所有组均应用 CLP 诱导的脓毒症模型。检查脑、肺、肝和心脏的组织病理学损伤,并通过免疫组织化学法测定 caspase-3、p-NF-κB、TNF-α、IL-1β 和 IL-6 水平。采用 ELISA 法检测血清 TNF-α、IL-1β、IL-6、IL-10 水平。JWH-133 治疗降低了脑、心、肺和肝的组织病理学损伤,并降低了这些组织中 caspase-3、p-NF-κB、TNF-α、IL-1β 和 IL-6 的水平。此外,JWH-133 治疗还降低了因 CLP 而增加的血清 TNF-α、IL-1β 和 IL-6 水平,并增加了抗炎细胞因子 IL-10 水平。在本研究中,确定 CB2 受体激动剂 JWH-133 可降低 CLP 诱导的炎症,并减轻脑、肺、肝和心脏的损伤。我们的研究结果表明,用 JWH-133 激活 CB2 受体在脓毒症中具有治疗潜力。

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