羌活水提物预先给药对CCI大鼠神经病理性疼痛的预防作用及机制研究
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摘要
目的探讨羌活水提物预先给药对神经慢性结扎损伤(CCI)大鼠神经病理性疼痛的预防作用及机制研究。方法将50只SD大鼠按随机数字表分为假手术组、模型组、羌活低剂量组、羌活中剂量组和羌活高剂量组,制备CCI大鼠模型,假手术组只暴露神经不进行结扎。羌活各剂量组给予不同剂量羌活水提物,假手术组和模型组给予等量生理盐水。术后14 d,大鼠进行机械痛阈测定后处死,取脊髓腰膨大L4～L6节段,检测并比较不同组大鼠脊髓组织中三叉神经节嘌呤能P2X4受体(P2X4R)、转录因子-κB(NF-κB)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)水平。结果与假手术组比较,术后其余各组机械痛阈均降低,脊髓组织中P2X4R、NF-κB、IL-1β和TNF-α表达水平均增高,差异具有统计学意义(P <0.05);与模型组比较,术后羌活各剂量组机械痛阈均增加,脊髓组织中P2X4R、NF-κB、IL-1β和TNF-α表达水平均降低,差异具有统计学意义(P <0.05);羌活各剂量组机械痛阈随羌活剂量的增加而增加,脊髓组织中P2X4R、NF-κB、IL-1β和TNF-α表达水平随羌活剂量的增加而均降低,差异具有统计学意义(P <0.05)。结论羌活水提物能缓解大鼠神经病理性疼痛,其作用机制可能与抑制脊髓中P2X4R的表达,降低了NF-κB和促炎因子水平有关。
Objective: To investigate the preventive effect and mechanism of pre-administration of rhizoma notopterygii aqueous extract on neuropathic pain in chronic constrictive injury(CCI) rats. Methods: 50 SD rats were randomly divided into the sham operation group,the model group,low-dose group,middle-dose group and high-dose group. The sham operation group only had its nerves exposed. The different dose groups received rhizoma notopterygii aqueous extract with difference concentration,while the sham operation group and the model group received the normal saline. On the postoperative 14 d,the mechanical withdrawal threshold was measured.P2 X4 R,NF-κB,IL-1β and TNF-α levels at the spinal cord(L4～L6) were detected and compared. Results: Compared with the sham-operated group,the mechanical pain threshold of other groups decreased,and the expression levels of P2 X4 R,NF-κB,IL-1β and TNF-α in spinal cord tissue were increased,with statistical significance(P <0.05). Compared with the model group,the mechanical pain threshold of other groups increased,and the expression levels of P2 X4 R,NF-κB,IL-1β and TNF-α in spinal cord tissue were decreased,with statistical significance(P < 0.05). The mechanical pain threshold increased with dose,and the expression levels of P2 X4 R,NF-κB,IL-1β and TNF-α in spinal cord decreased with dose,with statistical significance(P < 0.05). Conclusion: Rhizoma notopterygii aqueous extract can effectively ameliorate the neuropathic pain in rats,whose mechanism may be related to the inhibition of P2 X4 R expression in the spinal cord and the decrease of NF-κB and pro-inflammatory factors.
Objective: To investigate the preventive effect and mechanism of pre-administration of rhizoma notopterygii aqueous extract on neuropathic pain in chronic constrictive injury(CCI) rats. Methods: 50 SD rats were randomly divided into the sham operation group,the model group,low-dose group,middle-dose group and high-dose group. The sham operation group only had its nerves exposed. The different dose groups received rhizoma notopterygii aqueous extract with difference concentration,while the sham operation group and the model group received the normal saline. On the postoperative 14 d,the mechanical withdrawal threshold was measured.P2 X4 R,NF-κB,IL-1β and TNF-α levels at the spinal cord(L4～L6) were detected and compared. Results: Compared with the sham-operated group,the mechanical pain threshold of other groups decreased,and the expression levels of P2 X4 R,NF-κB,IL-1β and TNF-α in spinal cord tissue were increased,with statistical significance(P <0.05). Compared with the model group,the mechanical pain threshold of other groups increased,and the expression levels of P2 X4 R,NF-κB,IL-1β and TNF-α in spinal cord tissue were decreased,with statistical significance(P < 0.05). The mechanical pain threshold increased with dose,and the expression levels of P2 X4 R,NF-κB,IL-1β and TNF-α in spinal cord decreased with dose,with statistical significance(P < 0.05). Conclusion: Rhizoma notopterygii aqueous extract can effectively ameliorate the neuropathic pain in rats,whose mechanism may be related to the inhibition of P2 X4 R expression in the spinal cord and the decrease of NF-κB and pro-inflammatory factors.
引文
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[18]田坤,孟路阳,陈世伟.利伐沙班对下肢动脉硬化闭塞症大鼠血管内皮功能及p38MAPK/NF-κB通路的影响[J].中国药师,2018,21(5):757-760.
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[20]凌晓敏,宋瑞雪,刘邱阿雪,等.右美托咪定对神经病理性疼痛模型大鼠天门冬氨酸及白细胞介素1β水平的影响[J].中国临床药理学杂志,2016,32(17):1599-1601.
[2]Pickering G,Marcoux M,Chapiro S,et al.An algorithm for neuropathic pain management in older people[J].Drugs&Aging,2016,33(8):1-9.
[3]罗鑫,王雪晶,赵祎武,等.羌活化学成分研究[J].中草药,2016,47(9):1492-1495.
[4]刘虹,陈朝晖,刘洋.脊髓背角参与神经病理性疼痛分子机制的进展[J].临床麻醉学杂志,2016,12(2):200-203.
[5]Murrelllagnado RD.A role for P2X4 receptors in lysosome function[J].Journal of General Physiology,2018,150(2):185-187.
[6]金争,李冬,闫东梅,等.TRIM蛋白家族调节NF-κB信号通路的研究进展[J].中国免疫学杂志,2017,33(6):924-929.
[7]Zheng W,Tao Z,Cai L,et al.Chrysin attenuates IL-1β-induced expression of inflammatory mediators by suppressing NF-κB in human osteoarthritis chondrocytes[J].Inflammation,2017,40(4):1143-1154.
[8]Bao G,Li C,Qi L,et al.Tetrandrine protects against oxygenglucose-serum deprivation/reoxygenation-induced injury via PI3K/AKT/NF-κB signaling pathway in rat spinal cord astrocytes[J].Biomedicine&Pharmacotherapy,2016,84(14):925-930.
[9]Bennett GJ,Xie YK.A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man[J].Pain,1988,33(1):87-107.
[10]盛璇,李桂林.嘌呤受体在神经元和神经胶质细胞间信息传递中的作用[J].中国药理学通报,2017,33(4):450-454.
[11]Kasuya G,Fujiwara Y,Takemoto M,et al.Structural insights into divalent cation modulations of ATP-Gated P2X receptor channels[J].Cell Reports,2016,14(4):932-944.
[12]Mendiolaprecoma J,Padilla K,Rodríguezcruz A,et al.Theobromine-induced changes in A1 purinergic receptor gene expression and distribution in a rat brain alzheimer′s disease model[J].Journal of Alzheimers Disease,2017,55(3):1273-1283.
[13]徐啸翔,曹烨,丁婷婷,等.三叉神经节嘌呤能P2X4受体参与(牙合)干扰致大鼠咬肌痛觉过敏的研究[J].中华口腔医学杂志,2016,51(3):176-181.
[14]王富江,李芮琳,贾壮壮,等.注射用丹参多酚酸和血栓通注射液联合应用对局灶性脑缺血再灌注大鼠脑组织星形胶质细胞和小胶质细胞的影响及作用机制研究[J].中草药,2017,48(19):4029-4036.
[15]薛芸,梁尚栋.钙信号在糖尿病周围神经病变中感觉神经元和神经胶质细胞功能异常的研究进展[J].中国药理学通报,2017,33(3):308-311.
[16]Matsumura Y,Yamashita T,Sasaki A,et al.A novel P2X4 receptor-selective antagonist produces anti-allodynic effect in a mouse model of herpetic pain[J].Scientific Reports,2016,6(2):32461-32472.
[17]Zheng Z,Du X,Zhang K,et al.Olfactory ensheathing cell transplantation inhibits P2X4 receptor overexpression in spinal cord injury rats with neuropathic pain[J].Neuroscience Letters,2017,651(10):171-176.
[18]田坤,孟路阳,陈世伟.利伐沙班对下肢动脉硬化闭塞症大鼠血管内皮功能及p38MAPK/NF-κB通路的影响[J].中国药师,2018,21(5):757-760.
[19]Ratajczyk E,Ledzewicz U,Leszczynski M,et al.The role of TNF-αinhibitor in glioma virotherapy:A mathematical model[J].Mathematical Biosciences&Engineering Mbe,2017,14(1):305-314.
[20]凌晓敏,宋瑞雪,刘邱阿雪,等.右美托咪定对神经病理性疼痛模型大鼠天门冬氨酸及白细胞介素1β水平的影响[J].中国临床药理学杂志,2016,32(17):1599-1601.