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多糖通过调节 ROS 和 TLR-4-NF-B 通路对肝缺血再灌注损伤的抗炎抗氧化作用。

Anti-Inflammatory and Antioxidant Effect of Polysaccharide in Hepatic Ischemia-Reperfusion Injury by Regulating ROS and the TLR-4-NF-B Pathway.

机构信息

Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000 Guizhou, China.

Department of Biochemistry and Molecular Biology, Zunyi Medical University, Zunyi, 563000 Guizhou, China.

出版信息

Biomed Res Int. 2020 May 25;2020:1860637. doi: 10.1155/2020/1860637. eCollection 2020.

Abstract

polysaccharide (EUP) has been shown to have anti-inflammatory and antioxidant effects. However, the mechanism underlying these effects has rarely been reported, and whether EUP can reduce liver injury in hepatic ischemia-reperfusion injury (HIRI) has not been reported. In this study, 40 Sprague-Dawley (SD) rats were randomly divided into 5 groups: the sham group, ischemia-reperfusion (I/R) group, and three EUP pretreatment groups (320 mg/kg, 160 mg/kg, and 80 mg/kg). SD rats were pretreated with EUP by gavage once a day prior to I/R injury for 10 days. Except for the sham group, blood flow in the middle and left liver lobes was blocked in all the other groups, resulting in 70% liver ischemia, and the ischemia and reperfusion times were 1 h and 4 h, respectively. Ischemic liver tissue and serum were obtained to detect biochemical markers and liver histopathological damage. Compared with the I/R group, after EUP pretreatment, serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-, and interleukin-1 levels were significantly decreased, malondialdehyde levels in liver tissues were significantly decreased, superoxide dismutase levels were significantly increased, and the area of liver necrosis was notably reduced. To understand the specific mechanism involved, we determined the levels of Toll-like receptor- (TLR-) 4-nuclear factor-kappaB (NF-B) pathway-associated proteins in vivo and in vitro. The data showed that EUP can reduce liver damage by decreasing ROS levels and inhibiting TLR-4-NF-B pathway activation and may be a promising drug in liver surgery to prevent HIRI.

摘要

多糖(EUP)已被证明具有抗炎和抗氧化作用。然而,这些作用的机制很少有报道,EUP 是否可以减轻肝缺血再灌注损伤(HIRI)中的肝损伤尚未报道。在这项研究中,将 40 只 Sprague-Dawley(SD)大鼠随机分为 5 组:假手术组、缺血再灌注(I/R)组和 EUP 预处理组(320mg/kg、160mg/kg 和 80mg/kg)。SD 大鼠在 I/R 损伤前每天通过灌胃给予 EUP 预处理 10 天。除假手术组外,其余各组均阻断中肝叶和左肝叶的血流,导致 70%的肝缺血,缺血和再灌注时间分别为 1 小时和 4 小时。获得缺血性肝组织和血清以检测生化标志物和肝组织病理学损伤。与 I/R 组相比,EUP 预处理后,血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、肿瘤坏死因子-α和白细胞介素-1 水平显著降低,肝组织丙二醛水平显著降低,超氧化物歧化酶水平显著升高,肝坏死面积明显减少。为了了解具体的作用机制,我们在体内和体外测定了 Toll 样受体-(TLR-)4-核因子-κB(NF-κB)途径相关蛋白的水平。数据表明,EUP 通过降低 ROS 水平和抑制 TLR-4-NF-κB 途径激活来减轻肝损伤,可能是肝外科预防 HIRI 的一种有前途的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d344/7273391/6dd5e41b5e99/BMRI2020-1860637.001.jpg

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