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目的 :探讨鞘内间断多次给予N-甲基-D-天门冬氨酸(N-methyl-D-aspartate,NMDA)受体拮抗剂对坐骨神经分支选择性损伤模型(spared nerve injury,SNI)大鼠神经病理性疼痛的缓解作用及其可能的机制。方法:雄性SD大鼠72只,体质量240~260 g,采用随机数字表法,将大鼠随机分为6组(n=12):假手术组(S组)、坐骨神经分支选择性损伤组(NP组)、氯胺酮低剂量组(K1组)、氯胺酮高剂量组(K2组)、MK-801低剂量组(M1组)、MK-801高剂量组(M2组)。S组仅暴露坐骨神经,NP组、K1组、K2组、M1组、M2组制备坐骨神经分支选择性损伤模型。从术后1 d开始,K1组、K2组、M1组、M2组鞘内分别注射氯胺酮50μg、氯胺酮100μg、MK-801 5μg和MK-801 10μg,容量均为10μl,S组和NP组鞘内注射生理盐水10μl,1次/d,连续给药7 d。分别于术前1 d和术后1~7 d,进行疼痛行为学观察和机械刺激缩足反射阈值(paw withdrawal mechanical threshold,PWMT)测定。所有大鼠均于术后第7天处死,免疫组化观察大鼠脊髓L4~6节段背角胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)和碱性成纤维细胞生长因子(basic fibroblast growth factor,b FGF)表达变化,Western blot检测脊髓L4~6节段b FGF蛋白含量变化。结果:术后第7天给药前和给药后,NP组术侧PWMT较S组明显降低(P=0.000),K1组、K2组、M1组和M2组术侧PWMT较NP组明显升高(P=0.000)。免疫组化结果显示,NP组术侧b FGF、GFAP蛋白表达量较S组明显升高(P=0.000);K1组、K2组、M1组和M2组bFGF、GFAP蛋白表达量较NP组明显降低(P=0.000)。Western blot结果显示,NP组b FGF蛋白表达量较S组明显升高(P=0.000);K1组、K2组、M1组和M2组b FGF蛋白表达量较NP组明显降低(P=0.000)。结论:鞘内间断多次给予NMDA受体拮抗剂可缓解SNI引起的大鼠痛觉过敏,其机制可能与抑制b FGF蛋白表达及星形胶质细胞活化有关。
Objective: To investigate the effect of multiple intrathecal N-methyl-D-aspartate (NMDA) receptor antagonists on the spiking nerve injury (SNI) Alleviating effect of rat neuropathic pain and its possible mechanism. Methods: Seventy two male Sprague Dawley rats weighing 240-260 g were randomly divided into 6 groups (n = 12): sham operation group (S group), sciatic nerve branch selective injury group (NP group), ketamine low dose group (K1 group), ketamine high dose group (K2 group), MK-801 low dose group (M1 group) and MK-801 high dose group (M2 group). S group only exposed the sciatic nerve, NP group, K1 group, K2 group, M1 group, M2 group preparation sciatic nerve branch selective injury model. K1, K2, M1 and M2 groups were intrathecally injected with 50 μg of ketamine, 100 μg of ketamine, 5 μg of MK-801 and 10 μg of MK-801, all at a dose of 10 μL intrathecally in group S and group NP Injection of saline 10μl, 1 / d, continuous administration of 7 d. Pain behavioral observation and mechanical stimulation of paw withdrawal mechanical threshold (PWMT) were performed on the first day before operation and from 1 to 7 days after operation. All rats were sacrificed on the 7th day after operation. Immunohistochemistry was used to observe the expressions of glial fibrillary acidic protein (GFAP) and basic fibroblast growth factor, b FGF) expression changes, Western blot detection of spinal cord L4 ~ 6 b bFGF protein content. Results: Before operation and after administration, the level of PWMT in NP group was significantly lower than that in S group (P = 0.000). The level of PWMT in group K1, K2, M1 and M2 was significantly higher than that in NP group High (P = 0.000). Immunohistochemistry showed that the expression of bFGF and GFAP in NP group was significantly higher than that in S group (P = 0.000). The expression of bFGF and GFAP protein in group K1, K2, M1 and M2 were significantly higher than that in NP group Decreased (P = 0.000). Western blot showed that the expression of b FGF protein in NP group was significantly higher than that in S group (P = 0.000); b FGF protein expression in K1, K2, M1 and M2 groups was significantly lower than that in NP group (P = 0.000) . Conclusion: Multiple intrathecal administration of NMDA receptor antagonists can relieve hyperalgesia induced by SNI in rats. The mechanism may be related to the inhibition of b FGF protein expression and the activation of astrocytes.