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甘草酸对大鼠肝脏缺血再灌注损伤的保护作用及可能相关的信号通路。

The protective effect of glycyrrhizin on hepatic ischemia-reperfusion injury in rats and possible related signal pathway.

作者信息

Kou Xiaoni, Zhu Jiang, Xie Xinke, Hao Mingxia, Zhao Yingren

机构信息

Department of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710000, Shaanxi Province, China.

Department of Hepatopathy, Affiliated hospital of Shaanxi University of Chinese Medicine, Xianyang 712000, Shaanxi Province, China.

出版信息

Iran J Basic Med Sci. 2020 Sep;23(9):1232-1238. doi: 10.22038/ijbms.2020.44101.10334.

Abstract

OBJECTIVES

To investigate the protective effect of glycyrrhizin (GL) on hepatic ischemia-reperfusion injury (HIRI).

MATERIALS AND METHODS

Forty SD rats were randomly divided into sham group, HIRI group, GL 100 mg/kg group, and GL 200 mg/kg group. The pathological alterations of liver tissue in each group were observed. The levels of alanine transaminase (ALT), aspartate aminotransferase (AST), endothelin-1 (ET-l), nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were detected. Western blot was used to detect the expression levels of cytoplasmic protein caspase-3, Bax, Bcl-2, heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear protein Nrf2.

RESULTS

Compared with the HIRI group, the levels of AST, ALT, ET-1, TNF-α, IL-1β, and IL-6 in GL groups were lower, serum NO content was higher, MDA content was lower, SOD and GSH-Px activities were significantly increased, apoptosis index was lower (0.05), which was more obvious in high-dose GL (200 mg/kg) group. The LC3-II/LC3-I ratio and Beclin-1 protein expression levels in the GL group were significantly lower than the HIRI group, but the expression levels of cytoplasmic protein HO-1 and nuclear protein Nrf2 were significantly higher than those of the HIRI group, which was more obvious in the high-dose GL group (0.05).

CONCLUSION

GL has a protective effect on the liver of HIRI rats, and its mechanism may be related to activation of the Nrf2/HO-1 signaling pathway, inhibition of oxidative stress, inflammation, autophagy, and apoptosis.

摘要

目的

探讨甘草酸(GL)对肝缺血再灌注损伤(HIRI)的保护作用。

材料与方法

将40只SD大鼠随机分为假手术组、HIRI组、GL 100mg/kg组和GL 200mg/kg组。观察各组肝组织的病理变化。检测丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、内皮素-1(ET-1)、一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽过氧化物酶(GSH-Px)的水平。采用蛋白质免疫印迹法检测细胞质蛋白半胱天冬酶-3、Bax、Bcl-2、血红素加氧酶-1(HO-1)、核因子E2相关因子2(Nrf2)以及核蛋白Nrf2的表达水平。

结果

与HIRI组相比,GL组的AST、ALT、ET-1、TNF-α、IL-1β和IL-6水平较低,血清NO含量较高,MDA含量较低,SOD和GSH-Px活性显著增加,凋亡指数较低(P<0.05),高剂量GL(200mg/kg)组更为明显。GL组的LC3-II/LC3-I比值和Beclin-1蛋白表达水平显著低于HIRI组,但细胞质蛋白HO-1和核蛋白Nrf2的表达水平显著高于HIRI组,高剂量GL组更为明显(P<0.05)。

结论

GL对HIRI大鼠肝脏具有保护作用,其机制可能与激活Nrf2/HO-1信号通路、抑制氧化应激、炎症、自噬和凋亡有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7adc/7491491/4f8c96ea75ae/IJBMS-23-1232-g001.jpg

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