NMDA受体拮抗剂对神经病理性疼痛大鼠脊髓背角bFGF表达的影响

发布时间：2018-03-27 13:59

本文选题：碱性成纤维细胞生长因子　切入点：氯胺酮　出处：《重庆医科大学学报》2016年01期

【摘要】：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。
[Abstract]:Objective: to investigate the effect of N-methyl-Daspartate N-methyl-D-aspartate receptor antagonist on neuropathic pain induced by selective injury of sciatic nerve branches in rats with intrathecal intermittent administration of N-methyl-D-aspartate and its possible mechanism. 72 male SD rats, The body mass is 240 ~ 260g, and the random digital table method is used. Rats were randomly divided into 6 groups: sham operation group (S group), sciatic nerve branch selective injury group (NP-group), ketamine low-dose group (K1), ketamine high-dose group (K2), MK-801 low-dose group (M1 group), MK-801 high dose group (M2 group), group S (group S) only exposed to MK-801, MK-801, MK-801, MK-801, MK-801 and MK-801. The selective injury model of sciatic nerve branching was established in group K1, group K1, group K2, group M 1, group M 2, group K2, group K2, group K2, group K2, group K2, group K2, group K2, group K2, group K1, group K1, group K1, group K1, group K1, group K1, group K1, group K1, group K1, group K1, group K1, group K1, group K2, group K1, group K1, group K1, group K2, group K1, group K1, group K2. In NP group, intrathecal injection of normal saline 10 渭 l / d was given continuously for 7 days. The pain behavior and mechanical stimulation reflex threshold of paw withdrawal mechanical threshold were measured 1 day before operation and 1 day after operation. All the rats were killed on the 7th day after operation. Immunohistochemical study on the expression of glial fibrillary acidic protein in dorsal horn of rat spinal cord L4 ~ (6) and basic fibroblast growth factor-B (FGFs). Western blot was used to detect the protein content of b FGF in L4 ~ (6) segment of spinal cord. Results: after operation, the content of b FGF in L4 ~ (6) segment of spinal cord was determined by Western blot. On the 7th day after administration, the PWMT of the operative side in the NP group was significantly lower than that in the S group. The PWMT in the operative side of the K2 group and the M2 group was significantly higher than that of the NP group. Immunohistochemical results showed that the expression of bFGFGFAP protein in the operative side of the NP group was significantly higher than that in the S group, and the expression of PWMT in the operative side of the NP group was significantly higher than that in the S group. The results of Western blot showed that the expression of bFGFGFAP in K2 group was significantly higher than that in group S group (P < 0.05). Conclusion: the expression of bFGFGFAP protein in group M 1 and group M 2 is significantly lower than that in group NP. Conclusion: the results showed that the expression of b FGF protein was significantly higher in group C than in group C (P < 0.05). Conclusion: the expression of b FGF protein in group M 1 and group M 2 is significantly lower than that in group NP (P < 0.01). Conclusion: the expression of b FGF in group C is significantly higher than that in group S. Conclusion:. Repeated intrathecal administration of NMDA receptor antagonists alleviated hyperalgesia induced by SNI in rats. The mechanism may be related to the inhibition of the expression of b FGF protein and the activation of astrocytes.
【作者单位】：重庆医科大学附属第一医院麻醉科;
【基金】：重庆市卫生局医学科研计划资助项目(编号:2012-1-018) 重庆市医学重点学科(编号:渝卫科教[2007]2号) 卫生部国家临床重点专科建设经费资助项目(编号:财社[2011]170号)
【分类号】：R741

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