七氟醚通过 JAK2-STAT3 通路对大鼠肝缺血再灌注损伤的影响。

Effect of sevoflurane on hepatic ischemia-reperfusion injury in rats via JAK2-STAT3 pathway.

机构信息

Department of Anesthesiology, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang City, Henan Province, China.

出版信息

Eur Rev Med Pharmacol Sci. 2019 Feb;23(3):1350-1356. doi: 10.26355/eurrev_201902_17030.

DOI:10.26355/eurrev_201902_17030

PMID:30779103

Abstract

OBJECTIVE

To investigate the effect of sevoflurane on hepatic ischemia-reperfusion injury in rats via janus kinase 2/signal transducer and activator of transcription 3 (JAK2-STAT3) pathway.

MATERIALS AND METHODS

Forty healthy male Sprague-Dawley (SD) rats were randomly divided into sham group (n=10), model group (HIRI group, n=10), sevoflurane intervention group (SF group, n=10), and sevoflurane combined with AG490 intervention group (AG490 group, n=10). Liver and serum samples were collected after reperfusion for 6 h. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), interleukin (IL) -1β, IL-6 and tumor necrosis factor (TNF) -α were detected by enzyme-linked immunosorbent assay (ELISA). JAK2, STAT3, p-JAK2 and p-STAT3 were detected by Western-blot. The expression level of cobalt quenching technique was used to detect the permeability of mitochondrial membrane permeability transition pore (mPTP).

RESULTS

The levels of ALT, AST, AKP, IL-1β, IL-6 and TNF-α in HIRI group were higher than those in sham group (p < 0.05), those in SF group were lower than those in HIRI group (p < 0.05), while those in AG490 group were higher than those in SF group (p < 0.05). The levels of JAK2 protein, pJAK2 protein, STAT3 protein and P STAT3 protein in HIRI group were lower than those in sham group (p < 0.05); the levels of each protein in SF group were higher than those in HIRI group (p < 0.05), while those in AG490 group were lower than those in SF group (p < 0.05). The open degree of HIRI group was higher than that of sham group (p < 0.05); SF group was lower than that of HIRI group, and AG490 group was higher than that of SF group (p < 0.05).

CONCLUSIONS

Sevoflurane can significantly improve HIRI and reduce hepatic immune inflammation in rats. The mechanism may be related to activating JAK2-STAT3 pathway and inhibiting the overopening of mPTP.

摘要

目的

通过 Janus 激酶 2/信号转导和转录激活因子 3（JAK2-STAT3）通路研究七氟醚对大鼠肝缺血再灌注损伤的影响。

材料与方法

40 只健康雄性 Sprague-Dawley（SD）大鼠随机分为假手术组（n=10）、模型组（HIRI 组，n=10）、七氟醚干预组（SF 组，n=10）和七氟醚联合 AG490 干预组（AG490 组，n=10）。再灌注 6 h 后采集肝、血清样本。采用酶联免疫吸附试验（ELISA）检测血清丙氨酸转氨酶（ALT）、天门冬氨酸转氨酶（AST）、碱性磷酸酶（AKP）、白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子（TNF）-α水平。采用 Western-blot 检测 JAK2、STAT3、p-JAK2 和 p-STAT3。采用钴猝灭技术检测线粒体膜通透性转换孔（mPTP）的通透性。

结果

HIRI 组 ALT、AST、AKP、IL-1β、IL-6 和 TNF-α水平高于假手术组（p<0.05），SF 组低于 HIRI 组（p<0.05），AG490 组高于 SF 组（p<0.05）。HIRI 组 JAK2 蛋白、pJAK2 蛋白、STAT3 蛋白和 p-STAT3 蛋白水平低于假手术组（p<0.05）；SF 组各蛋白水平高于 HIRI 组（p<0.05），AG490 组低于 SF 组（p<0.05）。HIRI 组的开放程度高于假手术组（p<0.05）；SF 组低于 HIRI 组，AG490 组高于 SF 组（p<0.05）。