青藤碱对神经病理性痛大鼠脊髓氧化应激反应的影响
发布时间：2019-02-13 20:52
【摘要】：目的评价青藤碱对神经病理性疼痛的疗效以及青藤碱对神经病理性痛大鼠脊髓背角神经元凋亡和脊髓氧化应激的影响,并探讨氧化应激在神经元凋亡中的作用,研究青藤碱的镇痛机制是否通过抑制脊髓的氧化应激和脊髓背角神经元凋亡而起作用的。方法 由兰州大学基础医学院实验动物中心提供鼠龄1.5-2月、200g左右的Wistar大鼠108只,将其随机分为3个实验组：假手术组(S组36只)、青藤碱注射液组(SIN组36只)和神经病理性痛组(CCI组36只)。S组不制备神经痛模型,只游离坐骨神经主干,另外两组大鼠用坐骨神经慢性压榨性损伤法制备Vistar大鼠神经病理性痛模型。SIN组腹腔注射青藤碱注射液4()mg/kg,1次/d,注射时间为术后大鼠苏醒后开始注射至处死前1d,S组和CCI组每日腹腔注射等容量(1.6ml/kg)生理盐水。在术前1d(TO)、术后3d(T1)、7d(T2)、14d(T3)时分别测定机械缩足反应阈(MWT)和热缩足潜伏期(TWL),在术后T1、T2、T3时分别测定痛阈后,每组取大鼠12只处死,取L4-6脊髓组织,其中6只大鼠L4-6脊髓组织用TUNEL法检测脊髓背角凋亡神经元,另外6只大鼠L4-6脊髓组织测定脊髓MDA含量及SOD活性,采用分光光度法,并进行氧化应激指标(MDA含量及SOD活性)与神经元凋亡的相关性分析。结果与S组比较,CCI组和SIN组大鼠的MWT值和TWL值于CCI术后T1-3时减小,神经元凋亡率升高,脊髓组织中MDA含量增多,SOD活性降低(P0.05)；与CCI组比较,SIN组大鼠的MWT值和TWL值于CCI术后T1-3时升高,脊髓背角神经元凋亡率降低,脊髓组织中MDA含量减少,SOD活性升高(P0.05)；脊髓组织中SOD活性与脊髓背角神经元凋亡率呈负相关(r=-0.973,p0.01),MDA含量与神经元凋亡率呈正相关(r=0.929,p0.01)。结论青藤碱可减轻大鼠神经病理性痛,青藤碱可减少神经病理性疼痛大鼠脊髓背角神经元调亡和抑制其脊髓氧化应激反应,青藤碱的镇痛机制可能是通过抑制脊髓氧化应激反应从而减少脊髓背角神经元凋亡起作用的。
[Abstract]:Objective to evaluate the effect of sinomenine on neuropathic pain and the effect of sinomenine on apoptosis of spinal cord dorsal horn neurons and oxidative stress of spinal cord in rats with neuropathic pain, and to explore the role of oxidative stress in neuronal apoptosis. To study whether the analgesic mechanism of sinomenine can inhibit oxidative stress of spinal cord and apoptosis of spinal dorsal horn neurons. Methods one hundred and eight Wistar rats, aged about 1.5 to 2 months, were randomly divided into 3 groups: sham operation group (S group, 36 rats), and sham operation group (group S, 36 rats). Sinomenine injection group (SIN group, 36 rats) and neuropathic pain group (CCI group, 36 rats) did not produce neuralgia model, but only dissociated sciatic nerve trunk. The other two groups of rats were treated with chronic sciatic nerve compression injury to make the neuropathic pain model of Vistar rats. SIN group was injected with sinomenine injection 4 () mg/kg,1 times per day. The injection time was that the rats were injected intraperitoneally with iso-volume (1.6ml/kg) normal saline (1.6ml/kg) 1 day before the rats were killed and the rats in group S and CCI were injected intraperitoneally with iso-volume (1.6ml/kg). Mechanical foot contraction threshold (MWT) and thermal contraction latency (TWL),) were measured at 3 (T1), 7 (T2) and 14 days (T3) after (TO),. 12 rats were killed in each group. The apoptotic neurons in the spinal cord of L4-6 rats were detected by TUNEL method. The content of MDA and the activity of SOD in the spinal cord of the other 6 rats were measured by spectrophotometry. The correlation between oxidative stress index (MDA content and SOD activity) and neuronal apoptosis was analyzed. Results compared with group S, the values of MWT and TWL in CCI group and SIN group decreased at T1-3 after CCI, the rate of neuronal apoptosis increased, the content of MDA in spinal cord increased and the activity of SOD decreased (P0.05). Compared with CCI group, the MWT and TWL values of SIN group increased at T1-3 after CCI, the apoptosis rate of spinal dorsal horn neurons decreased, the content of MDA in spinal cord tissue decreased and the SOD activity increased (P0.05). There was a negative correlation between the activity of SOD and the apoptosis rate of spinal dorsal horn neurons (r ~ (-0.973) P _ (0.01), MDA) and the apoptotic rate of neurons (r ~ (0.929) P _ (0.01). Conclusion sinomenine can relieve neuropathic pain in rats and sinomenine can reduce the apoptosis of spinal dorsal horn neurons and inhibit the oxidative stress response of spinal cord in rats with neuropathic pain. The analgesic mechanism of sinomenine may reduce the apoptosis of spinal dorsal horn neurons by inhibiting oxidative stress in spinal cord.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R243.2
本文编号：2421875
[Abstract]:Objective to evaluate the effect of sinomenine on neuropathic pain and the effect of sinomenine on apoptosis of spinal cord dorsal horn neurons and oxidative stress of spinal cord in rats with neuropathic pain, and to explore the role of oxidative stress in neuronal apoptosis. To study whether the analgesic mechanism of sinomenine can inhibit oxidative stress of spinal cord and apoptosis of spinal dorsal horn neurons. Methods one hundred and eight Wistar rats, aged about 1.5 to 2 months, were randomly divided into 3 groups: sham operation group (S group, 36 rats), and sham operation group (group S, 36 rats). Sinomenine injection group (SIN group, 36 rats) and neuropathic pain group (CCI group, 36 rats) did not produce neuralgia model, but only dissociated sciatic nerve trunk. The other two groups of rats were treated with chronic sciatic nerve compression injury to make the neuropathic pain model of Vistar rats. SIN group was injected with sinomenine injection 4 () mg/kg,1 times per day. The injection time was that the rats were injected intraperitoneally with iso-volume (1.6ml/kg) normal saline (1.6ml/kg) 1 day before the rats were killed and the rats in group S and CCI were injected intraperitoneally with iso-volume (1.6ml/kg). Mechanical foot contraction threshold (MWT) and thermal contraction latency (TWL),) were measured at 3 (T1), 7 (T2) and 14 days (T3) after (TO),. 12 rats were killed in each group. The apoptotic neurons in the spinal cord of L4-6 rats were detected by TUNEL method. The content of MDA and the activity of SOD in the spinal cord of the other 6 rats were measured by spectrophotometry. The correlation between oxidative stress index (MDA content and SOD activity) and neuronal apoptosis was analyzed. Results compared with group S, the values of MWT and TWL in CCI group and SIN group decreased at T1-3 after CCI, the rate of neuronal apoptosis increased, the content of MDA in spinal cord increased and the activity of SOD decreased (P0.05). Compared with CCI group, the MWT and TWL values of SIN group increased at T1-3 after CCI, the apoptosis rate of spinal dorsal horn neurons decreased, the content of MDA in spinal cord tissue decreased and the SOD activity increased (P0.05). There was a negative correlation between the activity of SOD and the apoptosis rate of spinal dorsal horn neurons (r ~ (-0.973) P _ (0.01), MDA) and the apoptotic rate of neurons (r ~ (0.929) P _ (0.01). Conclusion sinomenine can relieve neuropathic pain in rats and sinomenine can reduce the apoptosis of spinal dorsal horn neurons and inhibit the oxidative stress response of spinal cord in rats with neuropathic pain. The analgesic mechanism of sinomenine may reduce the apoptosis of spinal dorsal horn neurons by inhibiting oxidative stress in spinal cord.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R243.2
【共引文献】
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