星状神经节离断对脊髓损伤大鼠中枢性疼痛行为及CREB SGK1 NF-κB蛋白表达的影响

Impacts of stellate ganglion neurotomy on central pain behavior and the expressions of CREB,SGK1 and NF-κB proteins in spinal cord injury rats

目的探究星状神经节离断对脊髓损伤(SCI)大鼠中枢性疼痛行为及环磷腺苷效应元件结合蛋白(CREB)、血清和糖皮质激素调节蛋白激酶1(SGK1)、核因子-κB(NF-κB)蛋白表达的影响。方法将SD大鼠按随机分配原则分为假手术组(Sham组)、模型组(Model组)、治疗组(Treat组)各6例。Model组、Treat组构建SCI模型,Sham组未使用铁球砸脊髓,其他步骤相同。Treat组在脊髓损伤后予星状神经节离断,通过BBB运动功能评分评价运动功能学,通过机械痛阈试验和热痛阈试验测量机械缩足反射阈值(PWT)和热缩足潜伏期(PWL),ELISA法检测血清白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、前列腺素E2(PGE2)水平,HE染色检测脊髓组织病理变化,TUNEL染色检测细胞凋亡,Western blot检测CREB、SGK1、NF-κB p65蛋白表达。结果Sham组大鼠脊髓组织结构完好,细胞呈正常形态,神经纤维分布均匀且行走规则。与Sham组相比,Model组脊髓组织及细胞完整性破坏严重,形成大量空洞,神经纤维排列紊乱,可见大量炎性细胞浸润,BBB运动功能评分、PWT、PWL值显著下降(P<0.05),IL-1β、TNF-α、PGE2水平、细胞凋亡数量、CREB、SGK1、NF-κB p65蛋白水平显著升高(P<0.05)。与Model组相比,Treat组脊髓组织结构形态明显改善,脊髓组织空洞化有所好转,炎性细胞浸润减少,神经纤维排列趋于正常,BBB运动功能评分、PWT、PWL值显著增加(P<0.05),IL-1β、TNF-α、PGE2水平、细胞凋亡数量、CREB、SGK1、NF-κB p65蛋白水平显著减少(P<0.05)。结论星状神经节离断可减轻SCI大鼠中枢性疼痛行为,降低CREB、SGK1、NF-κB蛋白水平。

Objective To investigate the impacts of stellate ganglion neurotomy on central pain behavior and the expressions of cAMP-response element binding protein(CREB),serum and glucocorticoid induced kinase1(SGK1)and nuclear factor-κB(NF-κB)proteins in spinal cord injury(SCI)rats.Methods SD rats were randomly separated into sham surgery group(Sham group),model group(Model group)and treatment group(Treat group),6 cases of each group.The Model group and Treat group constructed SCI models.The Sham underwent stellate ganglion dissection after spinal cord injury.The BBB motor function score was applied to evaluate motor function,the mechanical pain threshold experiment and thermal pain threshold experiment were applied to measure the paw withdrawal threshold(PWT)and paw withdrawal latency(PWL).ELISA was applied to detect serum levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and prostaglandin E2(PGE2).HE staining was applied to detect pathological changes in spinal cord tissue.TUNEL staining was applied to detect cell apoptosis.Western blot was applied to detect the expressions of CREB,SGK1,and NF-κB p65 proteins.Results The spinal cord tissue structure of rats in Sham group was intact,with normal cell morphology,uniform distribution of nerve fibers,and regular walking.Compared with the Sham group,the spinal cord tissue and cell integrity of the Model group were severely damaged,forming a large number of cavities,disordered arrangement of nerve fibers,and visible infiltration of a large number of inflammatory cells,the BBB motor function score,PWT,and PWL values were obviously decreased(P<0.05),the levels of IL-1β,TNF-α,PGE2,cell apoptosis,and the levels of CREB,SGK1,NF-κB p65 protein were obviously increased(P<0.05).Compared with the Model group,the spinal cord tissue structure and morphology of the Treat group were obviously improved,with improved spinal cord tissue cavitation,reduced inflammatory cell infiltration,and a normal arrangement of nerve fibers,the BBB motor function score,PWT,and PWL values were obviously increased(P<0.05),the levels of IL-1β,TNF-α,PGE2,cell apoptosis,and CREB,SGK1,NF-κB p65 protein were obviously decreased(P<0.05).Conclusion Stellate ganglion neurotomy can alleviate central pain behavior in SCI rats and reduce the levels of CREB,SGK1,and NF-κB proteins.