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秋水仙碱对肾缺血再灌注损伤所致肝损伤的潜在保护作用:Nrf2和NLRP3炎性小体的作用

The possible protective effect of colchicine against liver damage induced by renal ischemia-reperfusion injury: role of Nrf2 and NLRP3 inflammasome.

作者信息

Awad Azza Sayed, Elariny Hemat A, Sallam Amany Said

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Menoufia University, Menofia, Egypt.

出版信息

Can J Physiol Pharmacol. 2020 Dec;98(12):849-854. doi: 10.1139/cjpp-2020-0230. Epub 2020 Jul 8.

DOI:10.1139/cjpp-2020-0230
PMID:32640174
Abstract

Ischemia-reperfusion injury (IRI) induces an inflammatory response and production of reactive oxygen species, which affects the organs remote to the sites of renal IR. However, remote effects of renal IRI on the liver need further investigations. Renal injury associated with liver disease is a common clinical problem. Colchicine is an established drug for microtubule stabilization that may reduce tissue injury and has antioxidant and antiinflammatory effects. The aim of the present study was () to assess the hepatic changes after induction of renal IRI, () to explore the possible protective effect of colchicine on liver injury following renal IRI, and () to investigate the possible mechanisms underlying the potential effect. Forty rats were randomly divided into four groups: sham operation group, colchicine-treated group, IR group, and colchicine-treated IR group. Colchicine treatment improved liver function (ALT/AST) after renal IRI, decreased hepatic oxidative stress and cell apoptosis by reducing hepatic MDA, upregulating hepatic total antioxidant capacity, Nrf2, and HO-1. Furthermore, colchicine inhibited inflammatory responses by downregulating hepatic NLRP3 inflammasome, IL-1β, and caspase-1. Colchicine attenuates renal IRI-induced liver injury in rats. This effect may be due to reducing inflammation and oxidative stress markers.

摘要

缺血再灌注损伤(IRI)会引发炎症反应并产生活性氧,这会影响远离肾脏缺血再灌注部位的器官。然而,肾脏IRI对肝脏的远程影响仍需进一步研究。与肝脏疾病相关的肾损伤是一个常见的临床问题。秋水仙碱是一种已被认可的用于微管稳定的药物,它可能减轻组织损伤,具有抗氧化和抗炎作用。本研究的目的是:(1)评估肾脏IRI诱导后的肝脏变化;(2)探究秋水仙碱对肾脏IRI后肝损伤的可能保护作用;(3)研究潜在作用的可能机制。40只大鼠被随机分为四组:假手术组、秋水仙碱治疗组、IRI组和秋水仙碱治疗IRI组。秋水仙碱治疗改善了肾脏IRI后的肝功能(ALT/AST),通过降低肝脏丙二醛、上调肝脏总抗氧化能力、Nrf2和HO-1减少了肝脏氧化应激和细胞凋亡。此外,秋水仙碱通过下调肝脏NLRP3炎性小体、IL-1β和半胱天冬酶-1抑制炎症反应。秋水仙碱减轻了大鼠肾脏IRI诱导的肝损伤。这种作用可能是由于减少了炎症和氧化应激标志物。

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