海南医科大学学报2025，Vol.31Issue(17)：1327-1335,9.DOI:10.13210/j.cnki.jhmu.20250107.001
H2S通过JAK2/STAT3信号通路抑制新生大鼠缺氧缺血性脑病
H2S inhibits hypoxic-ischemic encephalopathy in juvenile rats through the JAK2/STAT3 signaling pathway
摘要
Abstract
Objective:To observe the effect of hydrogen sulfide donor sodium hydrosulfide(NaHS)on hypoxic-ischemic en-cephalopathy(HIE)in juvenile rats and exploration of its possible mechanism.Methods:Seven-day-old Wistar rats were subject-ed to double ligation of the right common carotid artery and placed in a hypoxic chamber to establish a neonatal rat model of HIE.NaHS(50 μmol/kg)was administered via intraperitoneal injection daily for 30 days.The condition of rats was observed and the weight of the rats was measured every day,and score for neurological deficits was calculated.TUNEL staining was used to ob-serve neuronal cell apoptosis in rat hippocampal tissue,and ELISA was used to detect the levels of interleukin-1β(IL-1β),IL-4,IL-6,and IL-10 in rat hippocampal tissue.The protein expression levels of arginase 1(Arg1),inducible nitric oxide synthase(iN-OS),phosphorylated JAK2(p-JAK2),and phosphorylated STAT3(p-STAT3)in rat hippocampal tissue were detected by Western blot.The effect of JAK2/STAT3 pathway agonist SC-39100 on the action of NaHS was observed.Results:Compared with the control group,the body weight of rats from day 4 to day 30 after modeling were significantly decreased,the neurological deficit score was significantly increased,the neuronal apoptosis in the hippocampal DG region was obviously increased,iNOS pro-tein expression was significantly upregulated,Arg1 protein expression was significantly downregulated,IL-4 and IL-10 levels were significantly decreased,IL-1 β and IL-6 levels were significantly increased,and p-JAK2 and p-STAT3 protein expression,as well as p-JAK2/t-JAK2 and p-STAT3/t-STAT3 ratios were significantly increased in the HIE model group(all P<0.05).Compared with the HIE model group,the body weight of rats from day 6 to day 30 after modeling were significantly increased,the neurological deficit score was significantly decreased,the neuronal apoptosis in the hippocampal DG region was obviously de-creased,iNOS protein expression was significantly downregulated,Arg1 protein expression was significantly upregulated,IL-4 and IL-10 levels were significantly increased,IL-1 β and IL-6 levels were significantly decreased,and p-JAK2 and p-STAT3 pro-tein expression,as well as p-JAK2/t-JAK2 and p-STAT3/t-STAT3 ratios were significantly decreased in the HIE+NaHS mod-el group(all P<0.05).SC-39100 reversed the effect of NaHS on reducing the neurological deficit score in HIE rats.Conclusion:Exogenous H2S has a protective effect on HIE in juvenile rats,and its mechanism may be related to activating the JAK2/STAT3 signaling pathway,inhibiting M1 polarization of microglia,inducing M2 polarization,and thereby inhibiting the neuroinflamma-tion.关键词
硫化氢/缺氧缺血性脑病/幼鼠/小胶质细胞极化/JAK2/STAT3信号通路Key words
Hydrogen sulfide/Hypoxic-ischemic encephalopathy/Juvenile rats/Microglia polarization/JAK2/STAT3 sig-naling pathway分类
医药卫生引用本文复制引用
刘剑锋,何攀,贺来彪,霍佳雯..H2S通过JAK2/STAT3信号通路抑制新生大鼠缺氧缺血性脑病[J].海南医科大学学报,2025,31(17):1327-1335,9.基金项目
This study was supported by Hunan Provincial Natural Science Foundation Project(2021JJ70036),Hengyang Science and Technology Plan Project(202150063524) （2021JJ70036）
Hunan Province Clinical Medical Technology Innovation Guidance Project(2020SK51702) 湖南省自然科学基金项目(2021JJ70036) （2020SK51702）
衡阳市科技计划项目(202150063524) （202150063524）
湖南省临床医疗技术创新引导项目(2020SK51702) （2020SK51702）
