依托咪酯调节AMPK/SIRT1/NF-κB信号通路对腰椎间盘突出症大鼠疼痛的影响OA
Effect of etomidate on pain in rats with lumbar disc herniation by regulating AMPK/SIRT1/NF-κB signaling pathway
目的 探讨依托咪酯(ET)调节腺苷酸激活蛋白激酶(AMPK)/沉默信息调节因子1(SIRT1)/核转录因子κB(NF-κB)信号通路对腰椎间盘突出症(LDH)大鼠疼痛的影响.方法 将72只SD大鼠随机分为6组,取1组作为对照组,其余大鼠采用自体髓核移植法建立LDH模型,并分为模型组(建模后给予等量生理盐水)、低剂量ET组(建模后给予1.5 mg/kg ET)、中剂量ET组(建模后给予3.0 mg/kg ET)、高剂量ET组(建模后给予6.0 mg/kg ET)、高剂量ET+AMPK抑制剂组(建模后给予6.0 mg/kg ET+0.2 mg/kg多索吗啡).分别检测各组大鼠压痛阈值和热痛阈值;HE染色观察大鼠腰椎组织形态学变化;ELISA检测血清中白细胞介素(IL)-1β、肿瘤坏死因子-α(TNF-α)、IL-6、P物质(SP)、神经肽Y(NPY)水平;水溶性四氮唑-1和硫代巴比妥酸法分别检测超氧化物歧化酶(SOD)和丙二醛(MDA)水平;Western blot检测腰椎组织中AMPK、p-AMPK、SIRT1、p65、p-p65蛋白表达.结果 与对照组相比,模型组大鼠腰椎间盘结构发生退行性变,压痛阈值、热痛阈值、SOD、p-AMPK/AMPK及SIRT1/GAPDH均显著降低(P<0.05),IL-1β、TNF-α、IL-6、SP、NPY、MDA水平及p-p65/p65均升高(P<0.05).与模型组相比,低、中、高剂量ET组大鼠腰椎间盘组织退行性变逐渐减轻,压痛阈值、热痛阈值、SOD、p-AMPK/AMPK、SIRT1/GAPDH均显著升高(P<0.05),IL-1β、TNF-α、IL-6、SP、NPY、MDA水平及p-p65/p65显著降低(P<0.05),且呈剂量依赖性.与高剂量ET组相比,高剂量ET+AMPK抑制剂组大鼠腰椎间盘结构发生退行性变,各指标变化趋势与高剂量组相反(P<0.05).结论 ET可能通过调控AMPK/SIRT1/NF-κB信号通路中关键蛋白的表达,抑制炎症和氧化应激的发生,缓解LDH大鼠的疼痛.
Objective To explore the effect of etomidate(ET)on pain in rats with lumbar disc herniation(LDH)by regulating the adenosine monophosphate activated protein kinase(AMPK)/silent information regulator 1(SIRT1)/nuclear factor-kappa B(NF-κB)signaling pathway.Methods A total of 72 SD rats were randomly divided into six groups.One group served as the control group,while the remaining rats underwent autologous nucleus pulposus transplantation to establish LDH models,and then were divided into the model group(given an equivalent volume of normal saline after modeling),the low-dose ET group(administered 1.5 mg/kg ET after modeling),the medium-dose ET group(administered 3.0 mg/kg ET after modeling),the high-dose ET group(administered 6.0 mg/kg ET after modeling),and the high-dose ET+AMPK inhibitor group(administered 6.0 mg/kg ET+0.2 mg/kg dorsomorphin after modeling).The pressure pain threshold and thermal pain threshold of rats in each group were measured separately.HE staining was used to observe morphological changes of lumbar spine tissue in rats.ELISA was used to detect the serum levels of interleukin(IL)-1β,tumor necrosis factor-alpha(TNF-α),IL-6,substance P(SP),and neuropeptide Y(NPY).Water-soluble tetrazolium salt-1 and thiobarbituric acid methods were performed to detect the levels of superoxide dismutase(SOD)and malondialdehyde(MDA),respectively.Western blot was performed to detect the expression levels of AMPK,p-AMPK,SIRT1,p65,and p-p65 proteins in lumbar spine tissue.Results Compared with the control group,the model group showed degenerative changes in lumbar disc structure,significantly decreased pressure pain threshold,thermal pain threshold,SOD,p-AMPK/AMPK and SIRT1/GAPDH(P<0.05),and significantly increased levels of IL-1β,TNF-α,IL-6,SP,NPY and MDA,and p-p65/p65(P<0.05).Compared with the model group,the low-,medium-,and high-dose ET groups showed gradually alleviated degenerative changes in lumbar disc tissue,significantly increased pressure pain threshold,thermal pain threshold,SOD,p-AMPK/AMPK and SIRT1/GAPDH(P<0.05),and significantly decreased levels of IL-1β,TNF-α,IL-6,SP,NPY,and MDA,and p-p65/p65(P<0.05),in a dose-dependent manner.Compared with the high-dose ET group,the high-dose ET+AMPK inhibitor group showed degenerative changes in the lumbar disc structure,and the trends of all indicators were opposite(P<0.05).Conclusion ET may alleviate pain in LDH rats by inhibiting inflammation and oxidative stress through regulating the expression of key proteins in the AMPK/SIRT1/NF-κB signaling pathway.
庞玉池;郭蒙帅
河北省沧州中西医结合医院麻醉科,河北 沧州 062650河北省沧州中西医结合医院脊柱脊髓手外科,河北 沧州 062650
医药卫生
依托咪酯AMPK/SIRT1/NF-κB信号通路腰椎间盘突出症疼痛
etomidateAMPK/SIRT1/NF-κB signaling pathwaylumbar disc herniationpain
《局解手术学杂志》 2026 (9)
781-786,6
沧州市重点研发计划指导项目(23244102187)
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