SOCS3 通过调控 JAK2/STAT3 信号通路对重症急性胰腺炎大鼠肺损伤的影响。
Effect of SOCS3 on lung injury in rats with severe acute pancreatitis through regulating JAK2/STAT3 signaling pathway.
机构信息
Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
出版信息
Eur Rev Med Pharmacol Sci. 2019 Nov;23(22):10123-10131. doi: 10.26355/eurrev_201911_19582.
OBJECTIVE
To explore the effect of suppressor of cytokine signaling 3 (SOCS3) on the lung injury in rats with severe acute pancreatitis (SAP) by regulating the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway.
MATERIALS AND METHODS
Sprague-Dawley rats were divided into control group (n=20) and SAP model group (established via injection of 5% sodium taurocholate, n=40). Then, SOCS3 was overexpressed using the adenovirus in 20 rats in SAP model group. The serum amylase (AMY) was detected, whether the transfection was successful was verified via quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR), the hepatic function indexes were detected, the pathological changes were observed using hematoxylin-eosin (HE) staining, and the wet/dry weight ratio (W/D) was calculated. Moreover, the content of serum inflammatory factors was detected via enzyme-linked immunosorbent assay (ELISA) and the expression levels of JAK2/STAT3 signaling pathway genes and proteins were detected through RT-PCR and Western blotting.
RESULTS
The content of AMY in SAP model group was significantly increased, indicating the successful modeling. SOCS3 was significantly increased in transfection group, suggesting that the transfection efficiency was significant. The content of alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in SOCS3 transfection group was significantly lower than in model group. According to the histopathological observation, there were lung injury, pulmonary edema, hemorrhage, severe inflammatory response, and alveolar congestion in SAP model group. There were almost no pathological changes in SOCS3 transfection group. In SOCS3 transfection group, the content of serum interleukin-6 (IL-6), IL-18 and tumor necrosis factor-α (TNF-α), the mRNA and protein expressions of IL-6, JAK2, and STAT3 were all remarkably declined.
CONCLUSIONS
SOCS3 inhibits the activation of the JAK2/STAT3 pathway and the increase of inflammatory factors, promoting the repair of lung injury in SAP rats.
目的
通过调节 Janus 激酶 2/信号转导子和转录激活子 3（JAK2/STAT3）通路，探讨细胞因子信号转导抑制因子 3（SOCS3）对重症急性胰腺炎（SAP）大鼠肺损伤的影响。
材料与方法
将 Sprague-Dawley 大鼠分为对照组（n=20）和 SAP 模型组（n=40，经 5%牛磺胆酸钠注射建立）。然后，在 SAP 模型组的 20 只大鼠中使用腺病毒过表达 SOCS3。检测血清淀粉酶（AMY），通过定量逆转录-聚合酶链反应（qRT-PCR）验证转染是否成功，检测肝功能指标，通过苏木精-伊红（HE）染色观察病理变化，并计算湿/干重比（W/D）。此外，通过酶联免疫吸附试验（ELISA）检测血清炎症因子含量，通过 RT-PCR 和 Western blot 检测 JAK2/STAT3 信号通路基因和蛋白的表达水平。
结果
SAP 模型组 AMY 含量明显升高，表明造模成功。转染组 SOCS3 明显升高，提示转染效率显著。SOCS3 转染组丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）含量明显低于模型组。根据组织病理学观察，SAP 模型组存在肺损伤、肺水肿、出血、严重炎症反应和肺泡充血，SOCS3 转染组几乎没有病理变化。在 SOCS3 转染组中，血清白细胞介素-6（IL-6）、IL-18 和肿瘤坏死因子-α（TNF-α）含量、IL-6、JAK2 和 STAT3 的 mRNA 和蛋白表达均明显下降。
结论
SOCS3 抑制 JAK2/STAT3 通路的激活和炎症因子的增加，促进 SAP 大鼠肺损伤的修复。
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