Intensive Care Unit, Foresea Life Insurance Guangzhou General Hospital, Guangzhou, Guangdong Province, China.
Department of Anesthesiology, Foresea Life Insurance Guangzhou General Hospital, Guangzhou, Guangdong Province, China.
J Biol Regul Homeost Agents. 2020 Sep-Oct;34(5):1719-1727. doi: 10.23812/20-326-A.
The purpose of this study was to investigate the influence of interleukin(IL)-22 on the Janus kinase/ signal transducer and activator of transcription 3 (JAK/STAT3) signaling pathway and sepsis-induced liver injury in rats. A total of 48 Sprague-Dawley rats were randomly divided into sham-operated group (n=12), model group (n=12), low-dose group (n=12) and high-dose group (n=12). Next, rat models of sepsis-induced liver injury were established through cecal ligation and puncture (CLP). At 12 h after surgery, blood was collected by heart puncture to detect liver function of the rats. It was found that the activity of alanine aminotransferase (ALT) and aspartame aminotransferase (AST) and the content of total bilirubin were reduced in low-dose group and high-dose group. Hematoxylin-eosin (HE) staining results revealed that after treatment with IL-22, the liver injury was relieved compared with model group. Moreover, the results of TUNEL staining assay revealed that the apoptosis level of liver cells declined after treatment with IL-22. Enzyme-linked immunosorbent assay (ELISA) results demonstrated that the levels of IL-6 and TNF-α were reduced, while the level of IL-10 was increased after treatment with IL-22. Moreover, it was discovered that the SOD content was overtly elevated in low-dose and high-dose groups compared with that in the model group. Finally, using Western blotting, it was confirmed that in comparison with the model group, the levels of Bcl-2/Bax and JAK/STAT3 signaling pathway-related proteins were markedly raised, while the level of Caspase-3 was decreased in the low-dose and high-dose groups. In conclusion, IL-22 can improve liver function, reduce the apoptosis level of liver cells, the expression of apoptosis-related proteins and the release of inflammatory factors, and alleviate liver injury by activating the JAK/STAT3 signaling pathway.
本研究旨在探讨白细胞介素（IL）-22 对大鼠 Janus 激酶/信号转导和转录激活因子 3（JAK/STAT3）信号通路及脓毒症诱导性肝损伤的影响。将 48 只 Sprague-Dawley 大鼠随机分为假手术组（n=12）、模型组（n=12）、低剂量组（n=12）和高剂量组（n=12）。采用盲肠结扎穿孔（CLP）法建立脓毒症诱导性肝损伤大鼠模型，术后 12 h 经心脏穿刺采血检测大鼠肝功能。结果发现，低剂量组和高剂量组大鼠丙氨酸氨基转移酶（ALT）和天门冬氨酸氨基转移酶（AST）活性及总胆红素含量降低。苏木精-伊红（HE）染色结果显示，与模型组相比，IL-22 治疗后肝损伤减轻。TUNEL 染色结果显示，IL-22 治疗后肝细胞凋亡水平下降。酶联免疫吸附试验（ELISA）结果显示，IL-22 治疗后 IL-6 和 TNF-α 水平降低，IL-10 水平升高。此外，与模型组相比，低剂量组和高剂量组 SOD 含量明显升高。Western blot 结果证实，与模型组相比，低剂量组和高剂量组 Bcl-2/Bax 和 JAK/STAT3 信号通路相关蛋白水平升高，Caspase-3 水平降低。综上所述，IL-22 可通过激活 JAK/STAT3 信号通路改善肝功能，降低肝细胞凋亡水平、凋亡相关蛋白表达及炎症因子释放，从而减轻肝损伤。
