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热休克蛋白 70(HSP70)通过高压氧预处理减轻肝缺血/再灌注损伤大鼠模型中的肝炎症和氧化损伤。

Heat Shock Protein 70 (HSP70) Reduces Hepatic Inflammatory and Oxidative Damage in a Rat Model of Liver Ischemia/Reperfusion Injury with Hyperbaric Oxygen Preconditioning.

机构信息

Department of Surgery, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan.

Department of Emergency Medicine, Chi-Mei Medical Center, Tainan, Taiwan.

出版信息

Med Sci Monit. 2018 Nov 12;24:8096-8104. doi: 10.12659/MSM.911641.

DOI:10.12659/MSM.911641
PMID:30417859
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6243869/
Abstract

BACKGROUND Several clinical conditions can cause hepatic ischemia/reperfusion (I/R) injury. This study aimed to determine the mechanism of the protective effect of hyperbaric oxygen preconditioning (HBO₂P) on hepatic ischemia/reperfusion (I/R) injury in a rat model, and to investigate the effects on HBO₂P and I/R injury of blocking HSP70 using antibody (Ab) pretreatment. MATERIAL AND METHODS Male Sprague-Dawley rats underwent HBO₂P for 60 min at 2.0 atmosphere absolute (ATA) pressure for five consecutive days before surgical hepatic I/R injury, performed by clamping the portal vein and hepatic lobe. Four groups studied included: the non-HBO₂P+ non-I/R group, which underwent sham surgery (N=10); the non-HBO₂P + I/R group (N=10); the HBO₂P + I/R group (N=10); and the HBO₂P + HSP70-Ab + I/R group (N=10) received one dose of HSP70 antibody one day before hepatic I/R injury. Serum lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and hepatic malondialdehyde (MDA) and myeloperoxidase (MPO) were measured biochemically. Rat liver tissues were examined histologically. RESULTS In rats with hepatic I/R injury without HSP70 antibody pre-treatment, HBO₂P significantly reduced hepatic injury and levels of LDH, AST, ALT, TNF-α, IL-6, MDA, and MPO levels; in comparison, the group pre-treated with an antibody to inhibit HSP70 (the HBO₂P + HSP70-Ab + I/R group) showed significant reversal of the beneficial effects of HBO₂P on hepatic I/R injury (p<0.05). CONCLUSIONS In a rat model of hepatic I/R injury with HBO₂P, HSP70 reduced hepatic inflammatory and oxidative damage.

摘要

背景

多种临床病症可导致肝脏缺血/再灌注(I/R)损伤。本研究旨在确定高压氧预处理(HBO₂P)对肝脏 I/R 损伤的保护机制,并探讨 HSP70 阻断抗体(Ab)预处理对 HBO₂P 和 I/R 损伤的影响。

材料和方法

雄性 Sprague-Dawley 大鼠在手术性肝 I/R 损伤前,连续 5 天,每天在 2.0 绝对大气压(ATA)下接受 60 分钟的 HBO₂P。肝 I/R 损伤通过夹闭门静脉和肝叶来完成。研究共分为 4 组:非 HBO₂P+非 I/R 组(n=10),进行假手术;非 HBO₂P+I/R 组(n=10);HBO₂P+I/R 组(n=10);HBO₂P+HSP70-Ab+I/R 组(n=10),在肝 I/R 损伤前一天接受一次 HSP70 抗体治疗。通过生化方法检测血清乳酸脱氢酶(LDH)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)、促炎细胞因子肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)以及肝丙二醛(MDA)和髓过氧化物酶(MPO)水平。检查大鼠肝组织的组织学变化。

结果

在未预先用 HSP70 抗体预处理的肝 I/R 损伤大鼠中,HBO₂P 显著减轻肝损伤和 LDH、AST、ALT、TNF-α、IL-6、MDA 和 MPO 水平;相比之下,用 HSP70 抗体抑制(HBO₂P+HSP70-Ab+I/R 组)预处理的大鼠组,HBO₂P 对肝 I/R 损伤的有益作用明显逆转(p<0.05)。

结论

在 HBO₂P 治疗的肝 I/R 损伤大鼠模型中,HSP70 减轻了肝的炎症和氧化损伤。

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