右美托咪定通过上调PPAR⁃γ改善神经病理性疼痛模型大鼠的痛觉敏化  

Dexmedetomidine ameliorates hyperalgesia of rat models with neuropathic pain via upregulation of PPAR-γ

作　　者：朱锋 钟粤 邓义江 刘文值 边疆 ZHU Feng;ZHONG Yue;DENG Yijiang;LIU Wenzhi;BIAN Jiang(Department of Anesthesiology,Affiliated Hospital of Panzhihua University,Panzhihua,617000;Department of Anesthesiology,Panzhihua Central Hospital,Panzhihua 617000,China)

机构地区：[1]攀枝花学院附属医院麻醉科,四川攀枝花617000 [2]攀枝花市中心医院麻醉科,四川攀枝花617000

出　　处：《基础医学与临床》2023年第9期1369-1374,共6页Basic and Clinical Medicine

基　　金：四川省科技厅应用基础项目(2021YJ0168)。

摘　　要：目的探究右美托咪定(DEX)对选择性坐骨神经损伤(SNI)大鼠的镇痛作用及潜在机制。方法将大鼠随机分为对照组,模型(SNI)组、DEX组、DEX+GW9662组,每组12只。SNI术后1~14 d,DEX组鞘内注射右美托咪定2μg/kg(10μL),DEX+GW9662组鞘内注射右美托咪定2μg/kg+PPAR-γ抑制剂(GW9662)300μg(10μL),对照组及SNI组仅鞘内注射相同容积的溶剂。于SNI术前1 d、术后3、7、14 d,检测大鼠的患肢足底的疼痛程度。于SNI术后14 d,用免疫荧光染色检测各组大鼠脊髓背角Iba-1的表达;Western blot检测患肢同侧脊髓背角Iba-1和PPAR-γ的表达;ELISA检测脊髓背角IFN-γ、IL-6含量。结果SNI术后7、14 d,SNI组大鼠患肢足底疼痛程度较对照组增加,并伴有同侧脊髓背角Iba-1、PPAR-γ、IL-6、IFN-γ表达上调(P<0.05);DEX组大鼠患肢足底疼痛程度较SNI组明显减轻,并且同侧脊髓背角Iba-1、PPAR-γ、IL-6、IFN-γ的表达明显降低(P<0.05);DEX+GW9662组大鼠患肢足底疼痛程度以及脊髓背角Iba-1、PPAR-γ、IL-6、IFN-γ的表达量较DEX组均明显增加(P<0.05)。结论右美托咪定显著改善SNI模型大鼠的痛觉敏化现象,其镇痛机制可能与上调脊髓背角PPAR-γ有关。Objective To explore the analgesic effect and underlying mechanisms of dexmedetomidine(DEX)with spared nerve injury(SNI)rat model.Methods Forty-eight SD rats were randomly divided into control group,SNI group,DEX group and DEX+GW9662 group,with 12 rats in each.From first day to 14th days after SNI surgery,rats in DEX group were intra-thecally injected with 2μg/kg(10μL)of dexmedetomidine,rats in DEX group were intrathecally injected with 2μg/kg of dexmedetomidine+300μg of PPAR-γinhibitor(GW9662),while rats in control and SNI groups were intrathecally injected with equal volume of solvent.At day 1 before operation,day 3,7,14 after operation,paw withdrawal threshold and thermal withdrawal latency were detected to evaluate the pain intensity.At post-operative day 14,immunofluorescence staining was used to detect the expression of Iba-1 in spinal dorsal horn,Western blot was used to detect the expression of Iba-1 and PPAR-γin ipsilateral spinal dorsal horn,ELISA was used to detect the levels of IFN-γand IL-6 in ipsilateral spinal dorsal horn.Results On postoperative day 7 and 14,compared with control group,the pain intensity of ipsilateral hind paw and the expression of Iba-1,PPAR-γ,IL-6 and IFN-γin ipsilateral spinal dorsal horn were enhanced in SNI group(P<0.05).Compared with SNI group,the pain intensity of ipsilateral hind paw and the expression of Iba-1,PPAR-γ,IL-6 and IFN-γin ipsilateral spinal dorsal horn decreased in EDX group(P<0.05).Compared with DEX group,the pain intensity of ipsilateral hind paw and the expression of Iba-1,PPAR-γ,IL-6 and IFN-γin ipsilateral spinal dorsal increased in DEX+GW9662 group(P<0.05).Conclusions Dexmedetomidine obviously inhibits pain sensitization of SNI rats.The underlying analgesic mechanism may be related to the up-regulation of PPAR-γin spinal dorsal horn.

关 键 词：右美托咪定 神经病理性疼痛 小胶质细胞 过氧化酶体增殖因子-γ(PPAR-γ) 

分 类 号：R338[医药卫生—人体生理学]