电针联合甲强龙对椎间盘脱出大鼠的有效性和安全性研究
|
摘要
目的观察电针联合甲强龙与单独使用电针或甲强龙对椎间盘脱出24 h后大鼠模型的肢体运动功能和神经细胞尼氏小体的影响,为临床合理应用提供依据。方法将112只SD大鼠随机分为假手术组(Sham)、模型组(Model)、预先电针联合甲强龙组(EA+MP)、电针组(EA)和甲强龙组(MP),采用自制硅胶垫片压迫法制备椎间盘脱出模型,各组分别进行处理,并在不同时间点进行BBB肢体运动功能评分或采集脊髓组织Nissl染色观察神经细胞尼氏小体的变化,以及副作用和死亡率。结果 1)BBB评分,各组在治疗后均呈上升趋势,EA+MP组在第3、7天时压迫侧后肢与EA组和MP组相比显著升高(P<0.05),第14天时各组均显著高于Model组(P<0.05),并与Sham组接近(P> 0.05)。(2)Nissl染色可见,与模型组相比各治疗组神经细胞损坏程度轻,尼氏小体数量多,其中EA+MP组优于其他两组。(3)副作用发生率,MP组为30%,EA+MP组为4.16%,EA组为0;死亡率,MP组为20%,EA+MP组和EA组为0。结论 3种治疗方案均可不同程度增加尼氏小体数量,维持神经细胞形态,改善椎间盘脱出24 h(超过甲强龙作用时间窗)大鼠的肢体运动功能。其中,EA+MP效果最佳,且显著降低了MP疗法的副作用和死亡率的发生,也优于单独EA的疗效。
Objective To observe the effects of electroacupuncture combined with methylprednisolone sodium succinate and electroacupuncture or methylprednisolone sodium succinate alone for intervertebral disc extrusion. The effects on the limb movement function and Nissl bodies of rat models after 24 h were analyzed, and the incidence of side effects in each group was analyzed to provide a basis for clinical application. Methods A total of 112 SD rats were randomly divided into sham operation group(Sham), model group(Model), electroacupuncture before methylprednisolone sodium succinate group(EA+MP), electroacupuncture group(EA), and methylprednisolone sodium succinate group(MP). The intervertebral disc extrusion model was prepared using a custom-made silicone gasket compression method. Each group was treated separately, and the BBB limb motor function score or Nissl staining of spinal cord tissue was observed at different time points to observe the changes of nerve cell Nissl bodies, as well as side effects and mortality. Results 1) BBB scores showed an upward trend in all groups after treatment, while on the third day and seventh day in the EA+MP group, the average BBB scores of hindlimbs of the compression side were significantly higher than those of the EA group and the MP group(P<0.05). Moreover, on the 14 th day, each group was significantly higher than the Model group(P< 0.05) and was close to the Sham group(P>0.05).(2) Nissl staining showed that, compared with the levels in the model group, the damage of nerve cells in each treatment group was mild, and the number of Nissl bodies was high. The average BBB scores of EA+MP group was superior to the other two groups in Nissl bodies protection.(3) The incidence of side effects was 30% in the MP group, 4.16% in the EA+MP group, and 0% in the EA group. The mortality rate in the MP group was 20%, while that in the EA+MP and EA groups was 0%. Conclusions The three treatment regimens increase the number of Nissl bodies to varying degrees, maintaine neuronal cell morphology, and improved limb motor function in rats with intervertebral disc extrusion for 24 h(more than the time window for methylprednisolone sodium succinate). Among the regimens, EA+MP has the best effect, significantly reduce the side effects and mortality rate of MP therapy, and produce a better curative effect than EA alone.
Objective To observe the effects of electroacupuncture combined with methylprednisolone sodium succinate and electroacupuncture or methylprednisolone sodium succinate alone for intervertebral disc extrusion. The effects on the limb movement function and Nissl bodies of rat models after 24 h were analyzed, and the incidence of side effects in each group was analyzed to provide a basis for clinical application. Methods A total of 112 SD rats were randomly divided into sham operation group(Sham), model group(Model), electroacupuncture before methylprednisolone sodium succinate group(EA+MP), electroacupuncture group(EA), and methylprednisolone sodium succinate group(MP). The intervertebral disc extrusion model was prepared using a custom-made silicone gasket compression method. Each group was treated separately, and the BBB limb motor function score or Nissl staining of spinal cord tissue was observed at different time points to observe the changes of nerve cell Nissl bodies, as well as side effects and mortality. Results 1) BBB scores showed an upward trend in all groups after treatment, while on the third day and seventh day in the EA+MP group, the average BBB scores of hindlimbs of the compression side were significantly higher than those of the EA group and the MP group(P<0.05). Moreover, on the 14 th day, each group was significantly higher than the Model group(P< 0.05) and was close to the Sham group(P>0.05).(2) Nissl staining showed that, compared with the levels in the model group, the damage of nerve cells in each treatment group was mild, and the number of Nissl bodies was high. The average BBB scores of EA+MP group was superior to the other two groups in Nissl bodies protection.(3) The incidence of side effects was 30% in the MP group, 4.16% in the EA+MP group, and 0% in the EA group. The mortality rate in the MP group was 20%, while that in the EA+MP and EA groups was 0%. Conclusions The three treatment regimens increase the number of Nissl bodies to varying degrees, maintaine neuronal cell morphology, and improved limb motor function in rats with intervertebral disc extrusion for 24 h(more than the time window for methylprednisolone sodium succinate). Among the regimens, EA+MP has the best effect, significantly reduce the side effects and mortality rate of MP therapy, and produce a better curative effect than EA alone.
引文
[1] Ito Y, Sugimoto Y, Tomioka M, et al. Does high dose methylprednisolone sodium succinate really improve neurological status in patient with acute cervical cord injury?: a prospective study about neurological recovery and early complications[J]. Spine, 2009, 34(20):2121.
[2] Pointillart V, Petitjean ME, Wiart L, et al. Pharmacological therapy of spinal cord injury during the acute phase[J]. Spinal Cord, 2000, 38 (2): 71-76.
[3] 卢知松, 陈益山, 姜代勋, 等. 椎间盘脱出大鼠模型的脊髓血流量变化及电针效应[J].中国实验动物学报, 2011,19(05):381-386Lu ZS, Chen YS, Jiang DX, et al. Changes of the spinal cord blood flow in rat models of intervertebral disc extrusion and the effect of electroacupuncture[J].Acta Lab Anim Sci Sin, 2011, 19(05):381-386
[4] Bracken MB, Shepard MJ, Holford TR, et al. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study[J]. JAMA, 1997, 277 (20): 1597-1604.
[5] Basso DM, Beattie MS, Bresnahan JC. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection[J]. Exp Neurol, 1996, 139 (2): 244-256.
[6] Bains M, Hall ED. Antioxidant therapies in traumatic brain and spinal cord injury[J]. Biochim Biophys Acta, 2012, 1822 (5): 675-684.
[7] Olby NJ, Sharp NJ, Munana KR, et al. Chronic and acute compressive spinal cord lesions in dogs due to intervertebral disc herniation are associated with elevation in lumbar cerebrospinal fluid glutamate concentration[J]. J Neurotrauma, 1999, 16 (12): 1215-1224.
[8] Forgione N, Fehlings MG. Rho-ROCK inhibition in the treatment of spinal cord injury[J]. World Neurosurg, 2014, 82 (3-4): e535-e539.
[9] Qu Y, Zhao J, Wang Y, et al. Silencing ephrinB3 improves functional recovery following spinal cord injury [J]. Mol Med Rep, 2014, 9 (5): 1761-1766.
[10] Bracken MB, Shepard MJ, Collins WF, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study[J]. N Engl J Med, 1990, 322 (20): 1405-1411.
[11] Bracken MB, Collins WF, Freeman DF, et al. Efficacy of methylprednisolone in acute spinal cord injury [J]. JAMA, 1984, 251 (1): 45-52.
[12] George ER, Scholten DJ, Buechler CM, et al. Failure of methylprednisolone to improve the outcome of spinal cord injuries[J]. Am Surg, 1995, 61 (8): 659-663, 663-664.
[13] Moore RW, Withrow SJ. Gastrointestinal hemorrhage and pancreatitis associated with intervertebral disk diseases in the dog [J]. J Am Vet Med Assoc, 1982, 180 (12): 1443-1447.
[14] Davies M. Pancreatitis, gastrointestinal ulceration and haemorrhage and necrotising cystitis following the surgical treatment of degenerative disc disease in a dachshund[J]. Vet Rec, 1985, 116(15):398-399.
[15] 陈武, 吴英伟, 郭泽领, 等. 中国畜牧兽医学会2003年学术年会论文集(小动物医学分册),中国北京:中国畜牧兽医学会2003年学术年会, 2003:4.Chen W, Wu YW, Guo ZL, et al. Chinese Association of Animal Science and Veterinary Medicine 2003 Annual Proceedings(Small animal medicine fascicule)[C].Beijing, China: Chinese Association of Animal Science and Veterinary Medicine 2003 Annual Conference, 2003:4.
[16] 陈武. 犬椎间盘病防治[J].中国动物保健, 2003(09):48-49.Chen W. Prevention and treatment of canine intervertebral disc disease[J].Chin Anim Health, 2003, (09):48-49.
[17] 李拓, 丛心宇, 孔学礼, 等. 比格犬胫神经皮层体感诱发电位正常值研究[J].中国农学通报, 2017, 33(5):112-115.Li T, Cong XY, Kong XL, et al. Normal value of tibial nerve somatosensory evoked potentials in beagle dogs[J]. Chin Agric Bull, 2017,33 (5):112-115.
[2] Pointillart V, Petitjean ME, Wiart L, et al. Pharmacological therapy of spinal cord injury during the acute phase[J]. Spinal Cord, 2000, 38 (2): 71-76.
[3] 卢知松, 陈益山, 姜代勋, 等. 椎间盘脱出大鼠模型的脊髓血流量变化及电针效应[J].中国实验动物学报, 2011,19(05):381-386Lu ZS, Chen YS, Jiang DX, et al. Changes of the spinal cord blood flow in rat models of intervertebral disc extrusion and the effect of electroacupuncture[J].Acta Lab Anim Sci Sin, 2011, 19(05):381-386
[4] Bracken MB, Shepard MJ, Holford TR, et al. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury. Results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. National Acute Spinal Cord Injury Study[J]. JAMA, 1997, 277 (20): 1597-1604.
[5] Basso DM, Beattie MS, Bresnahan JC. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop device versus transection[J]. Exp Neurol, 1996, 139 (2): 244-256.
[6] Bains M, Hall ED. Antioxidant therapies in traumatic brain and spinal cord injury[J]. Biochim Biophys Acta, 2012, 1822 (5): 675-684.
[7] Olby NJ, Sharp NJ, Munana KR, et al. Chronic and acute compressive spinal cord lesions in dogs due to intervertebral disc herniation are associated with elevation in lumbar cerebrospinal fluid glutamate concentration[J]. J Neurotrauma, 1999, 16 (12): 1215-1224.
[8] Forgione N, Fehlings MG. Rho-ROCK inhibition in the treatment of spinal cord injury[J]. World Neurosurg, 2014, 82 (3-4): e535-e539.
[9] Qu Y, Zhao J, Wang Y, et al. Silencing ephrinB3 improves functional recovery following spinal cord injury [J]. Mol Med Rep, 2014, 9 (5): 1761-1766.
[10] Bracken MB, Shepard MJ, Collins WF, et al. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the Second National Acute Spinal Cord Injury Study[J]. N Engl J Med, 1990, 322 (20): 1405-1411.
[11] Bracken MB, Collins WF, Freeman DF, et al. Efficacy of methylprednisolone in acute spinal cord injury [J]. JAMA, 1984, 251 (1): 45-52.
[12] George ER, Scholten DJ, Buechler CM, et al. Failure of methylprednisolone to improve the outcome of spinal cord injuries[J]. Am Surg, 1995, 61 (8): 659-663, 663-664.
[13] Moore RW, Withrow SJ. Gastrointestinal hemorrhage and pancreatitis associated with intervertebral disk diseases in the dog [J]. J Am Vet Med Assoc, 1982, 180 (12): 1443-1447.
[14] Davies M. Pancreatitis, gastrointestinal ulceration and haemorrhage and necrotising cystitis following the surgical treatment of degenerative disc disease in a dachshund[J]. Vet Rec, 1985, 116(15):398-399.
[15] 陈武, 吴英伟, 郭泽领, 等. 中国畜牧兽医学会2003年学术年会论文集(小动物医学分册),中国北京:中国畜牧兽医学会2003年学术年会, 2003:4.Chen W, Wu YW, Guo ZL, et al. Chinese Association of Animal Science and Veterinary Medicine 2003 Annual Proceedings(Small animal medicine fascicule)[C].Beijing, China: Chinese Association of Animal Science and Veterinary Medicine 2003 Annual Conference, 2003:4.
[16] 陈武. 犬椎间盘病防治[J].中国动物保健, 2003(09):48-49.Chen W. Prevention and treatment of canine intervertebral disc disease[J].Chin Anim Health, 2003, (09):48-49.
[17] 李拓, 丛心宇, 孔学礼, 等. 比格犬胫神经皮层体感诱发电位正常值研究[J].中国农学通报, 2017, 33(5):112-115.Li T, Cong XY, Kong XL, et al. Normal value of tibial nerve somatosensory evoked potentials in beagle dogs[J]. Chin Agric Bull, 2017,33 (5):112-115.