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锰超氧化物歧化酶模拟物对四氯化碳诱导的肝损伤的肝脏保护作用。

Hepatoprotective effects of Mimic of Manganese superoxide dismutase against carbon tetrachloride-induced hepatic injury.

作者信息

Wang Yan-Hong, Xu Xiang-Jiu, Li Hong-Ling

机构信息

Department of Pharmacy, Gansu Provincial Hospital, Lanzhou 730000, Gansu, China.

Division of Oncology, Gansu Provincial Hospital, Lanzhou 730000, Gansu, China.

出版信息

Int Immunopharmacol. 2014 Sep;22(1):126-32. doi: 10.1016/j.intimp.2014.06.016. Epub 2014 Jun 24.

Abstract

The aim of this study was to investigate the protective effects of Mimic of Manganese superoxide dismutase (MnSODm) against carbon tetrachloride (CCl(4))-induced hepatic injury in mice. Bifendate or MnSODm was intragastrically administered per day for 7 days. On the 8th day, all mice except the normal group were given 0.5% CCl(4)/peanut oil to induce hepatic injury model by intraperitoneal injection. Mice were sacrificed 24 h after CCl(4) treatment. Compared with the CCl(4) group, MnSODm significantly decreased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the serum and liver. Moreover, the contents of hepatic and serum malondialdehyde (MDA) and nitric oxide (NO) with inducible nitric oxide synthase (iNOS) activities were reduced. Histological findings also confirmed the antihepatotoxic characterization. In addition, MnSODm inhibited the pro-inflammatory mediators, such as prostaglandin E(2) (PGE(2)), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Further investigation showed that the inhibitory effect of MnSODm on the pro-inflammatory cytokines was associated with the down-regulation of nuclear factor-kappa B (NF-κB). In brief, our results show that the protective effect of MnSODm against CCl(4)-induced hepatic injury may rely on its ability to reduce oxidative stress and suppress inflammatory responses.

摘要

本研究旨在探讨锰超氧化物歧化酶模拟物(MnSODm)对四氯化碳(CCl₄)诱导的小鼠肝损伤的保护作用。每天经胃内给予联苯双酯或MnSODm,持续7天。在第8天,除正常组外的所有小鼠经腹腔注射0.5% CCl₄/花生油以诱导肝损伤模型。CCl₄处理24小时后处死小鼠。与CCl₄组相比,MnSODm显著降低了血清中天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)的活性,并增加了血清和肝脏中超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性。此外,肝脏和血清中丙二醛(MDA)的含量以及具有诱导型一氧化氮合酶(iNOS)活性的一氧化氮(NO)含量均降低。组织学结果也证实了其抗肝毒性特征。此外,MnSODm抑制了前列腺素E₂(PGE₂)、环氧化酶-2(COX-2)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)等促炎介质。进一步研究表明,MnSODm对促炎细胞因子的抑制作用与核因子-κB(NF-κB)的下调有关。简而言之,我们的结果表明,MnSODm对CCl₄诱导的肝损伤的保护作用可能依赖于其降低氧化应激和抑制炎症反应的能力。

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