普瑞巴林对CCI模型大鼠脊髓GFAP和SP表达的影响
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摘要
目的:观察普瑞巴林(pregabalin, PGB)对坐骨神经慢性压迫损伤(chronic constriction injury,CCI)模型大鼠的脊髓胶质纤维酸性蛋白(glial fibrillary acidic protein, GFAP)和P物质(substance P, SP)表达的影响。方法:SD大鼠随机分为3组(n=10),假手术组(S组)、CCI模型组(C组)、PGB组(P组),于术后第7天开始,P组每天一次PGB 60 mg/kg灌胃,S组和C组均给予同容积生理盐水。测定术前及术后第1、3、5、7、9、11、14 d大鼠机械刺激缩足反射阈值(paw withdrawal mechanical threshold,PWMT)和热刺激缩足反射潜伏期值(paw withdrawal thermal latency, PWTL)。免疫组化法测定大鼠脊髓背角内GFAP和P物质表达情况。结果:与S组相比,C组术后PWMT和PWTL明显降低,术后第7 d最为显著,GFAP及P物质表达明显上调,差异有统计学意义(P <0.05);与C组相比,P组治疗后各时间点PWMT和PWTL显著升高,GFAP和SP表达明显下降,差异显著(P <0.05)。结论:普瑞巴林能够抑制CCI模型大鼠脊髓背角GFAP和SP表达,减轻CCI模型大鼠痛觉过敏。
Objective: To investigate the effects of pregabalin(PGB) on the expression of glial fibrillary acidic protein(GFAP) and substance P in rats with chronic constriction injury(CCI) model. Methods: SD rats were randomly divided into three groups(n = 10), sham operation group(S), CCI group(C) and pregabalin treatment group(P). Rats in Group P were given PGB 60 mg/Kg once a day by intragastric infusion from the seventh day after the operation, while rats in Group S and Group C were given equal volume of saline. Paw withdrawal mechanical threshold(PWMT) and paw withdrawal thermal latency(PWTL) were measured before operation and at the day 1, 3, 5, 7, 9, 11, 14 after operation. The expression of GFAP and P substance was detected by immunohistochemical method. Results: Compared with Group S, PWMT and PWTL were significantly decreased in Group C, especially on the 7 th day after operation. The expression of GFAP and substance P was obviously upregulated(P < 0.05). Compared with Group C, PWTL and PWMT in Group P were increased significantly and the expression of GFAP and substance P were markedly downregulated(P < 0.05). Conclusion: Pregabalin can inhibit the expression of GFAP and substance P in CCI model rats, which may contribute to alleviation of neuropathic pain.
Objective: To investigate the effects of pregabalin(PGB) on the expression of glial fibrillary acidic protein(GFAP) and substance P in rats with chronic constriction injury(CCI) model. Methods: SD rats were randomly divided into three groups(n = 10), sham operation group(S), CCI group(C) and pregabalin treatment group(P). Rats in Group P were given PGB 60 mg/Kg once a day by intragastric infusion from the seventh day after the operation, while rats in Group S and Group C were given equal volume of saline. Paw withdrawal mechanical threshold(PWMT) and paw withdrawal thermal latency(PWTL) were measured before operation and at the day 1, 3, 5, 7, 9, 11, 14 after operation. The expression of GFAP and P substance was detected by immunohistochemical method. Results: Compared with Group S, PWMT and PWTL were significantly decreased in Group C, especially on the 7 th day after operation. The expression of GFAP and substance P was obviously upregulated(P < 0.05). Compared with Group C, PWTL and PWMT in Group P were increased significantly and the expression of GFAP and substance P were markedly downregulated(P < 0.05). Conclusion: Pregabalin can inhibit the expression of GFAP and substance P in CCI model rats, which may contribute to alleviation of neuropathic pain.
引文
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[15]司马蕾,樊碧发,徐仲煌,等.普瑞巴林治疗神经病理性癌痛的疗效和安全性研究.中华神经医学杂志,2016,15(10):1032~1035.
[16]Kim SY,Song JW,Park B,et al.Pregabalin reduces post-operative pain after mastectomy:a double-blind,randomized,placebo-controlled study.Acta Anaesthesiol Scand,2011,55(3):290~296.
[17]Seventer VR,Bach FW,Toth CC,et al.Pregabalin in the treatment of post-traumatic peripheral neuropathic pain:a randomized double-blind trial.Neurology,2006,67(10):1792~1800.
[18]Caiazzo M,Giannelli S,Valente P,et al.Direct conversion of fibroblasts into functional astrocytes by defined transcription factors.Stem Cell Reports,2015,4(1):25~36.
[19]孙涛,姚尚龙,宋文阁,等.鞘内注射氟代柠檬酸对神经病理性疼痛大鼠的镇痛作用.中华麻醉学杂志,2007,27(1):17~21.
[20]刁亮,梁伟,张永峰.NF-κB信号通路抑制剂对P物质作用后脊髓星形胶质细胞GFAP、炎性因子表达的影响.山东医药,2017,57(44):45~47.
[21]张恒,周占松,刘丽梅,等.P物质对脊髓星形胶质细胞活化和炎性因子TNF-α、IL-1β分泌的影响.第三军医大学学报,2006,28(7):681~684.
[2]Haanp??M,Nadine Attal.NeuPSIG guidelines on neuropathic pain assessment.Pain,2011,152(1):14~27.
[3]Hecke O,Austin SK,Khan RA,et al.Neuropathic pain in the general population:a systematic review of epidemiological studies,Pain,2014,155(4):654~662.
[4]查磊琼,彭志友,冯智英.神经病理性疼痛药物治疗新靶点研究进展.中国疼痛医学杂志,2018,24(6):402~406.
[5]Finnerup NB,Attal N,Haroutounian S,et al.Pharmacotherapy for neuropathic pain in adults:a systematic review and meta-analysis,Lancet Neurol,2015,14(2):162~173.
[6]Jha MK,Jeon S,Suk K.Glia as a link between neuroinflammation and Neuropathic Pain.Immune Netw,2012,12(2):41~47.
[7]Lebkuechner I,M?llerstr?m E,Wilhelmsson U,et al.Heterogeneity of Notch signaling in astrocytes and the effects of GFAP and vimentin deficiency.J Neurochem,2015;2:13202~13213.
[8]Shi P,Chen EY,Cs-Szabo G,et al.Biglycan inhibits capsaicin induced substance p release by cultured dorsal root ganglion neurons.Am J Phys Med Rehabil,2016,95(9):656~662.
[9]Bennett GJ,Xie YK.A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man.Pain,1988,33(1):87~107.
[10]Chaplan SR,Bach FW,Pogrel JW,et al.Quantitative assessment of tactile allodynia in the rat paw.J Neurosci Methods,1994,53:55~63.
[11]Martinez JA,Kasamatsu M,Rosales-Hernandez A,et al.Comparison of central versus peripheral delivery of pregabalin in neuropathic pain states.Mol Pain,2012,8:43~52.
[12]蔡捷,丁蕾,邢国刚,等.鞘内应用普瑞巴林对神经病理性大鼠的镇痛作用及其电生理学机制研究.中国疼痛医学杂志,2013,19(11):659~663.
[13]Gustafsson H,Sandin J.Oral pregabalin reverses cold allodynia in two distinct models of peripheral neuropathic pain.Eur J Pharmacol,2009,605:103~108.
[14]任士飞,张林吉,彭长凌.普瑞巴林对SNL模型大鼠镇痛作用及对脊髓背根神经节p-JNK表达的影响.中国疼痛医学杂志,2016,22(3):178~183.
[15]司马蕾,樊碧发,徐仲煌,等.普瑞巴林治疗神经病理性癌痛的疗效和安全性研究.中华神经医学杂志,2016,15(10):1032~1035.
[16]Kim SY,Song JW,Park B,et al.Pregabalin reduces post-operative pain after mastectomy:a double-blind,randomized,placebo-controlled study.Acta Anaesthesiol Scand,2011,55(3):290~296.
[17]Seventer VR,Bach FW,Toth CC,et al.Pregabalin in the treatment of post-traumatic peripheral neuropathic pain:a randomized double-blind trial.Neurology,2006,67(10):1792~1800.
[18]Caiazzo M,Giannelli S,Valente P,et al.Direct conversion of fibroblasts into functional astrocytes by defined transcription factors.Stem Cell Reports,2015,4(1):25~36.
[19]孙涛,姚尚龙,宋文阁,等.鞘内注射氟代柠檬酸对神经病理性疼痛大鼠的镇痛作用.中华麻醉学杂志,2007,27(1):17~21.
[20]刁亮,梁伟,张永峰.NF-κB信号通路抑制剂对P物质作用后脊髓星形胶质细胞GFAP、炎性因子表达的影响.山东医药,2017,57(44):45~47.
[21]张恒,周占松,刘丽梅,等.P物质对脊髓星形胶质细胞活化和炎性因子TNF-α、IL-1β分泌的影响.第三军医大学学报,2006,28(7):681~684.