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阿苯达唑改善急性肠系膜缺血再灌注损伤大鼠模型中的炎症反应。

Albendazole ameliorates inflammatory response in a rat model of acute mesenteric ischemia reperfusion injury.

作者信息

Badripour Abolfazl, Behzadi Mohamad, Hassanipour Amin, Azar Pasha Reza Shams, Rahbar Alireza, Abbaslou Zhaleh, Ehghaghi Elnaz, Piranviseh Ashkan, Khavandi Mohammad Mahdi, Ahmadi-Tafti Seyed Mohsen, Ashouri Mohammad, Soltani Zahra Ebrahim, Dehpour Ahmadreza

机构信息

Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran; Colorectal Surgery Research Center, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.

Department of Surgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Biomed Pharmacother. 2022 Sep;153:113320. doi: 10.1016/j.biopha.2022.113320. Epub 2022 Jun 22.

Abstract

BACKGROUND

Acute mesenteric ischemia is known as a life threatening condition. Re-establishment of blood flow in this condition can lead to mesenteric ischemia reperfusion (MIR) injury which is accompanied by inflammatory response. Still, clear blueprint of inflammatory mechanism underlying MIR injury has not been provided. Interestingly, Albendazole has exhibited notable effects on inflammation and cytokine production. In this study, we aimed to evaluate outcomes of MIR injury following pretreatment with Albendazole with respect to assessment of mesenteric inflammation and ischemia threshold.

METHODS

Male rats were randomly divided into sham operated, vehicle treated, Albendazole 100 mg/kg and Albendazole 200 mg/kg groups. MIR injury was induced by occlusion of superior mesenteric artery for 30 min followed by 120 min of reperfusion. Samples were utilized for assessment of epithelial survival and villous height. Immunohistochemistry study revealed intestinal expression of TNF-α and HIF-1-α. Gene expression of NF-κB/TLR4/TNF-α/IL-6 was measured using RTPCR. Also protein levels of inflammatory cytokines in serum and intestine were assessed by ELISA method.

RESULTS

Histopathological study demonstrated that pretreatment with Albendazole could ameliorate decline in villous height and epithelial survival following MIR injury. Also, systemic inflammation was suppressed after administration of Albendazole. Analysis of possible participating inflammatory pathway could demonstrate that intestinal expression of NF-κB/TLR4/TNF-α/IL-6 is significantly attenuated in treated groups. Eventually, IHC study illustrated concordant decline in mesenteric expression of HIF-1-α/TNF-α.

CONCLUSION

Single dose pretreatment with Albendazole could ameliorate inflammatory response and enhance ischemia threshold following induction of MIR injury. More studies would clarify existing causality in this phenomenon.

摘要

背景

急性肠系膜缺血是一种危及生命的疾病。在此情况下恢复血流可导致肠系膜缺血再灌注(MIR)损伤,并伴有炎症反应。然而,尚未提供MIR损伤潜在炎症机制的清晰蓝图。有趣的是,阿苯达唑已显示出对炎症和细胞因子产生有显著影响。在本研究中,我们旨在评估阿苯达唑预处理后MIR损伤的结果,以评估肠系膜炎症和缺血阈值。

方法

将雄性大鼠随机分为假手术组、溶剂处理组、100mg/kg阿苯达唑组和200mg/kg阿苯达唑组。通过阻断肠系膜上动脉30分钟,然后再灌注120分钟诱导MIR损伤。采集样本用于评估上皮细胞存活和绒毛高度。免疫组织化学研究显示肠道中TNF-α和HIF-1-α的表达。使用RTPCR测量NF-κB/TLR4/TNF-α/IL-6的基因表达。此外,通过ELISA法评估血清和肠道中炎性细胞因子的蛋白水平。

结果

组织病理学研究表明,阿苯达唑预处理可改善MIR损伤后绒毛高度的下降和上皮细胞存活。此外,阿苯达唑给药后全身炎症得到抑制。对可能参与的炎症途径分析表明,治疗组中NF-κB/TLR4/TNF-α/IL-6的肠道表达显著减弱。最终,免疫组织化学研究表明HIF-1-α/TNF-α的肠系膜表达一致下降。

结论

阿苯达唑单剂量预处理可改善MIR损伤诱导后的炎症反应并提高缺血阈值。更多研究将阐明这一现象中存在的因果关系。

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