[1]孙明阳,刘 海,齐曼曼,等.高压氧调控JAK2/STAT3通路对小鼠脊髓损伤的影响实验研究[J].陕西医学杂志,2025,54(5):612-617.[doi:DOI:10.3969/j.issn.1000-7377.2025.05.007]
　SUN Mingyang,LIU Hai,QI Manman,et al.Effects of hyperbaric oxygen on spinal cord injury in mice via regulation of the JAK2/STAT3 pathway[J].,2025,54(5):612-617.[doi:DOI:10.3969/j.issn.1000-7377.2025.05.007]
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高压氧调控JAK2/STAT3通路对小鼠脊髓损伤的影响实验研究
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《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年5期
页码:
612-617
栏目:
基础研究
出版日期:
2025-05-05

文章信息/Info

Title:
Effects of hyperbaric oxygen on spinal cord injury in mice via regulation of the JAK2/STAT3 pathway
作者:
孙明阳1; 刘 海2; 齐曼曼2; 李 明2; 段世博2
(1.唐山市人民医院神经外科,河北 唐山 063000; 2.沧州市中心医院,河北 沧州 061000)
Author(s):
SUN Mingyang1; LIU Hai2; QI Manman2; LI Ming2; DUAN Shibo2
(1.Department of Neurosurgery,Tangshan People's Hospital,Tangshan 063000,China; 2.Cangzhou Central Hospital,Cangzhou 061000,China)
关键词:
脊髓损伤;  高压氧;  Janus激酶2/信号转导和转录激活子3通路;  神经炎症;  神经细胞凋亡;  小鼠
Keywords:
Spinal cord injury;  Hyperbaric oxygen;  Janus kinase 2/signal transducer and activator of transcription 3 pathway;  Neuroinflammation;  Neuronal apoptosis;  Mice
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2025.05.007
文献标志码:
A
摘要:
目的:探讨高压氧调控Janus激酶2(JAK2)/信号转导和转录激活子3(STAT3)通路对小鼠脊髓损伤的影响。方法:将小鼠随机分为假手术组、脊髓损伤组、高压氧组、JAK2抑制剂(AG490)组和高压氧+JAK2激活剂(库马霉素)组,每组12只。假手术组小鼠仅暴露脊髓,其余组小鼠均通过Allen's击打法构建脊髓损伤模型。建模成功后,高压氧组小鼠行高压氧处理,尾静脉注射与AG490等量的0.9%氯化钠溶液; AG490组小鼠尾静脉注射5 mg/kg AG490; 高压氧+库马霉素组小鼠行高压氧处理,尾静脉注射6 mg/kg库马霉素; 假手术组、脊髓损伤组小鼠均尾静脉注射与AG490等量的0.9%氯化钠溶液。每日处理1次,共持续处理7 d。对各组小鼠进行巴索小鼠量表(BMS)评分; HE染色检测脊髓组织病理学改变; ELISA法检测脊髓组织中白细胞介素(IL)-10、IL-1β、肿瘤坏死因子-α(TNF-α)水平; TUNEL染色检测脊髓组织中神经细胞凋亡率; 免疫荧光染色检测脊髓组织中天冬氨酸特异性半胱氨酸蛋白酶-3(Caspase-3)阳性细胞平均荧光强度; Western blot检测脊髓组织中JAK2/STAT3通路蛋白表达。结果:与假手术组比较,脊髓损伤组小鼠脊髓组织中炎症细胞浸润明显,且有空泡形成,BMS评分、脊髓组织中IL-10水平降低,脊髓组织中IL-1β、TNF-α水平、神经细胞凋亡率、Caspase-3阳性细胞平均荧光强度及p-JAK2/JAK2、p-STAT3/STAT3比值升高(均P<0.05)。与脊髓损伤组比较,高压氧组、AG490组小鼠脊髓组织中炎症细胞浸润程度改善,空泡数量减少,BMS评分、脊髓组织中IL-10水平升高,脊髓组织中IL-1β、TNF-α水平、神经细胞凋亡率、Caspase-3阳性细胞平均荧光强度及p-JAK2/JAK2、p-STAT3/STAT3比值降低(均P<0.05)。高压氧+库马霉素组逆转了高压氧组上述指标变化。结论:高压氧可能通过抑制JAK2/STAT3通路减轻脊髓损伤小鼠神经炎症及神经细胞凋亡,促进下肢运动功能恢复。
Abstract:
Objective:To investigate the effects of hyperbaric oxygen on spinal cord injury in mice through the regulation of the Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway.Methods:Mice were randomly divided into sham operation group,spinal cord injury group,hyperbaric oxygen group,JAK2 inhibitor(AG490)group,hyperbaric oxygen+JAK2 activator(kumamycin)group,12 mice in each group.The sham operation group underwent only spinal cord exposure,while the other groups were subjected to spinal cord injury using the Allen's weight-drop method.After successful modeling,mice in the hyperbaric oxygen group were treated with hyperbaric oxygen and injected with 0.9% sodium chloride solution of the same volume as AG490 via tail vein.The AG490 group received intravenous injections of 5 mg/kg AG490,and the hyperbaric oxygen+kumamycin group received hyperbaric oxygen treatment and intravenous injections of 6 mg/kg kumamycin.Mice in the sham operation group and spinal cord injury group were injected with 0.9% sodium chloride solution of the same volume as AG490 via tail vein.Treatments were administered once daily for 7 consecutive days.Functional recovery was assessed using the Basso Mouse Scale(BMS).Histopathological changes in the spinal cord were examined by HE staining.Levels of interleukin(IL)-10,IL-1β,and tumor necrosis factor-α(TNF-α)in the spinal cord tissues were measured by ELISA.The rate of neuronal apoptosis was detected by TUNEL staining,and the mean fluorescence intensity of Caspase-3 positive cells was assessed by immunofluorescence staining.Expression of JAK2/STAT3 pathway proteins in the spinal cord tissues was analyzed by Western blot.Results:Compared with the sham operation group,the spinal cord injury group showed significant infiltration of inflammatory cells and formation of vacuoles in the spinal cord tissue of mice.The BMS score and IL-10 level in the spinal cord tissue decreased,while the levels of IL-1β,TNF-α,neuronal apoptosis rate,average fluorescence intensity of Caspase-3 positive cells,and the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 increased in the spinal cord tissue(all P<0.05).Compared with the spinal cord injury group,the infiltration degree of inflammatory cells in the spinal cord tissue of mice in the hyperbaric oxygen group and AG490 group improved,the number of vacuoles was reduced,the BMS score and IL-10 level in the spinal cord tissue increased,and the levels of IL-1β,TNF-α,neuronal apoptosis rate,average fluorescence intensity of Caspase-3 positive cells,and the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 in the spinal cord tissue decreased(all P<0.05).The hyperbaric oxygen+kumamycin group reversed the changes observed in the hyperbaric oxygen group.Conclusion:Hyperbaric oxygen may inhibit neuroinflammation and neuronal apoptosis in mice with spinal cord injury by inhibiting JAK2/STAT3 pathway,and promote the recovery of lower limb motor function.

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备注/Memo

备注/Memo:
[基金项目]河北省医学科学研究课题(20220368)
更新日期/Last Update: 2025-05-05