止痛灵凝胶对大鼠自体髓核移植致腰神经根性疼痛的影响及机理研究
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摘要
目的：观察止痛灵凝胶对大鼠腰神经根性疼痛的影响，并探讨其可能机理。方法：60只大鼠随机分为对照组、模型组、止痛灵组、扶他林组，建立大鼠自体髓核移植致腰5神经根性痛模型，造模后第3天起各组分别予生理盐水1ml、生理盐水1ml、止痛灵凝胶1g、扶他林乳胶剂1g外涂于腰部伤口两侧，每日2次，连续用药4周。造模后第31天测大鼠后肢机械刺激缩爪阈值、马尾神经根感觉神经传导速度和运动神经传导速度；取移植髓核和右侧L_5神经根作组织病理学观察(光镜、电镜)和免疫组化染色检测iNOS蛋白的表达；取移植髓核行免疫组化染色和RT-PCR，检测MMP-3、TIMP-1蛋白和mRNA表达。结果：止痛灵凝胶可显著降低模型大鼠后肢机械刺激缩爪阈值，提高马尾神经根传导速度，减轻髓核和神经根病理损害程度，下调髓核、神经根iNOS表达，下调髓核MMP-3蛋白及mRNA表达，上调TIMP-1蛋白及mRNA表达，改善MMP-3／TIMP-1比值失衡。结论：止痛灵凝胶具有抗腰椎间盘退变和抗神经根性痛作用，可能与抑制NO合成和改善MMP-3／TIMP—1失衡有关。
Objective To observe the effects of Zhitongling gelatum on lumbar root pain in rats and explore the possible mechanisms. Methods 60 rats were randomizd into 4 groups: control group, model group, Zhitongling group and Votalin group. The models of fifth lumbar root pain produced by transplantation of autologous nucleus pulposus in rats were created. 3 days after operation, all rats in each group were applied isotonic saline 1ml, isotonic saline 1ml, Zhitongling gelatum 1g and Votalin Emulgel 1g twice a day on the bilateralis of waist. The course of treatment was 4 weeks.On the 31~(st) day after operation, the posterior limb's retracting threshold for mechanical stimulation were determined. The sensory nerve and motor nerve conduction velocity of coccygeal nerve were measured. The histopathological change of transplanted nucleus pulposus and L_5 nerve root was observed by light microscope and electron microscope.The expression of iNOS protein in transplanted nucleus pulposus and L_5 nerve root was detected by EnVision immunohistochemical staining. The expression of MMP-3 and TIMP-1 protein and mRNA in transplanted nucleus pulposus were detected by EnVision immunohistochemical staining and RT-PCR. Results Zhitongling gelatum decreased the posterior limb's retracting thresholds for mechanical stimulation, elevated the nerves conduction velocity, relieved the degeneration of transplanted nucleus pulposus and nervous lesion in nerve root. Further more, it downregulated the expression of iNOS protein in transplanted nucleus pulposus and nerve root, downregulated the expression of MMP-3 protein and mRNA and up-regulated the expression of TIMP-1 protein and mRNA in transplanted nucleus pulposus, improved MMP-3/TIMP-1 ratios disequilibrium. Conclusions Zhitongling gelatum can relieve lumbar intervertebral disc degeneration and nerve root pain through inhibiting the synthesis of NO and improving MMP-3/TIMP-1 disequilibrium probably.
Objective To observe the effects of Zhitongling gelatum on lumbar root pain in rats and explore the possible mechanisms. Methods 60 rats were randomizd into 4 groups: control group, model group, Zhitongling group and Votalin group. The models of fifth lumbar root pain produced by transplantation of autologous nucleus pulposus in rats were created. 3 days after operation, all rats in each group were applied isotonic saline 1ml, isotonic saline 1ml, Zhitongling gelatum 1g and Votalin Emulgel 1g twice a day on the bilateralis of waist. The course of treatment was 4 weeks.On the 31~(st) day after operation, the posterior limb's retracting threshold for mechanical stimulation were determined. The sensory nerve and motor nerve conduction velocity of coccygeal nerve were measured. The histopathological change of transplanted nucleus pulposus and L_5 nerve root was observed by light microscope and electron microscope.The expression of iNOS protein in transplanted nucleus pulposus and L_5 nerve root was detected by EnVision immunohistochemical staining. The expression of MMP-3 and TIMP-1 protein and mRNA in transplanted nucleus pulposus were detected by EnVision immunohistochemical staining and RT-PCR. Results Zhitongling gelatum decreased the posterior limb's retracting thresholds for mechanical stimulation, elevated the nerves conduction velocity, relieved the degeneration of transplanted nucleus pulposus and nervous lesion in nerve root. Further more, it downregulated the expression of iNOS protein in transplanted nucleus pulposus and nerve root, downregulated the expression of MMP-3 protein and mRNA and up-regulated the expression of TIMP-1 protein and mRNA in transplanted nucleus pulposus, improved MMP-3/TIMP-1 ratios disequilibrium. Conclusions Zhitongling gelatum can relieve lumbar intervertebral disc degeneration and nerve root pain through inhibiting the synthesis of NO and improving MMP-3/TIMP-1 disequilibrium probably.
引文
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