首页|芍药甘草汤通过JAK2/STAT3信号通路对神经病理性疼痛大鼠的镇痛及对免疫调节机制影响

芍药甘草汤通过JAK2/STAT3信号通路对神经病理性疼痛大鼠的镇痛及对免疫调节机制影响

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目的 探寻芍药甘草汤对神经病理性疼痛(NP)的改善作用及其机制.方法 采用坐骨神经分支选择性损伤(SNI)法建立NP大鼠模型,模型制备成功后予以芍药甘草汤灌胃治疗14 d.治疗前后监测大鼠疼痛行为学指标变化,TUNEL染色检测脊髓背角细胞凋亡情况,免疫荧光组织化学法测定p-STAT3在脊髓中与Iba1的共定位情况,RT-PCR检测CD68、SOCS3、Arg-1的mRNA表达,ELISA检测白细胞介素-1 β(IL-1 β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)表达,Western blotting检测JAK2/STAT3通路蛋白表达.结果 与假手术组比较,模型组大鼠机械缩足阈值(MWT)、热缩足潜伏期(TWL)明显降低(P<0.01),脊髓背角中凋亡细胞显著增加(P<0.05),IL-1 β、1L-6 和 TNF-α 的表达显著增加(P<0.01),JAK2、p-JAK2、STAT3、p-STAT3 的表达显著增加(P<0.01),术后7、14 d的CD68、SOCS3 mRNA表达显著增加(P<0.01),Arg-1 mRNA表达显著降低(P<0.01).与模型组比较,芍药甘草汤组大鼠治疗后MWT、TWL明显上升(P<0.01),脊髓背角中凋亡细胞减少,IL-1β、IL-6、TNF-α的水平显著减少(P<0.01),JAK2、p-JAK2、STAT3、p-STAT3蛋白表达水平明显降低(P<0.01),CD68、SOCS3 mRNA表达显著减少(P<0.01),Arg-1 mRNA表达水平显著增加(P<0.01).结论 芍药甘草汤可能通过调控JAK2/STAT3通路调控小胶质细胞极化状态进而发挥改善NP的作用.
Analgesic Effect and Immunomodulatory Mechanism of Shaoyao Gancao Decoction on Neuropathic Pain Rats through JAK2/STAT3 Signaling Pathway
Objective:To explore the analgesic effect of Shaoyao Gancao Decoction(SGD)on neuropathic pain(NP)and its mechanism of action.Methods:Spared nerve injury(SNI)was adopted to establish a NP model in rats,which were treated with SGD gavage for 14 days.The behavioral changes in rats from each group were detect-ed before and after treatment.The apoptosis of spinal dorsal horn(SDH)was detected by TUNEL staining,and im-munofluorescence staining was used to determine the co-localization of p-STAT3 and Iba1.The expression of markers associated with different phenotypes of microglia(CD68,SOCS3,Arg-1)was examined by real-time RT-PCR.The expression of IL-1 β,IL-6 and TNF-α in SDH were evaluated by ELISA.The protein expressions of JAK2、p-JAK2,STAT3,p-STAT3 in SDH were determined by Western blotting.Results:Compared with the sham group,the model group showed significant decreases on the mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)in the right hind paw(P<0.01),the ratio of apoptotic cells in SDH increased significantly(P<0.05),the expressions of IL-1β,IL-6,TNF-α were significantly increased(P<0.01),JAK2,p-JAK2,STAT3,p-STAT3 protein expression increased significantly(P<0.01),CD68,SOCS3 mRNA expression was increased(P<0.01),while Arg-1 mRNA expression was decreased on the postoperative 7th and 14th days(P<0.01).Compared with the model group,the SGD group showed significant increases on the MWT and TWL in the right hind paw(P<0.01),the ratio of apoptotic cells in SDH decreased with no statistical difference,the expres-sions of IL-1β,IL-6,TNF-α were significantly decreased(P<0.01),JAK2,p-JAK2,STAT3,p-STAT3 protein ex-pression decreased significantly(P<0.01),CD68,SOCS3 mRNA expression was decreased(P<0.01),while Arg-1 mRNA expression was increased on the postoperative 7th and 14th days(P<0.01).Conclusion:SGD may partici-pate in the regulation of microglial polarization in NP rats by regulating the JAK2/STAT3 signaling pathway,thus exerting its analgesic action.

Neuropathic painShaoyao Gancao DecoctionMicrogliaNeuroinflammationJAK2/STAT3 signaling pathwayRats

杨浩、刘婷婷、曾荧、王敏、李炜、曾杰

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重庆市中医院,重庆 400021

重庆大学附属沙坪坝医院,重庆 400030

川北医学院,四川 南充 637100

神经病理性疼痛 芍药甘草汤 小胶质细胞 神经炎症 JAK2/STAT3通路 大鼠

重庆市科研机构绩效激励引导专项重庆市教委科学技术研究计划

jxyn2021-1-21KJQN202215116

2024

中国中医急症
中华中医药学会

中国中医急症

CSTPCD
影响因子:1.144
ISSN:1004-745X
年,卷(期):2024.33(4)
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