PI3K／Akt信号转导通路在EphB受体介导大鼠神经病理性痛中的作用  

Role of phosphatidylinositoi 3-kinase/protein-serine-threonine kinases signal transduction pathway in EphB receptor-mediated neuropathic pain in rats

作　　者：周学龙[1] 唐丽辉[1] 杨谨婷[1] 郁丽娜[2] 严敏[1] 

机构地区：[1]徐州医学院江苏省麻醉学重点实验室,221004 [2]浙江大学医学院附属第二医院麻醉科

出　　处：《中华麻醉学杂志》2012年第3期345-348,共4页Chinese Journal of Anesthesiology

摘　　要：目的探讨磷脂酰肌醇3-激酶（P13K）／丝氨酸-苏氨酸蛋白激酶（Akt）信号转导通路在EphB受体介导大鼠神经病理性痛中的作用。方法清洁级雄性SD大鼠48只，体重150～180g，2～3月龄，采用随机数字表法，将大鼠随机分为6组（n=8），C1组、E1组、C2组和E2组采用坐骨神经慢性压迫法（CCI）建立大鼠神经病理性痛模型，S1组和S2仅暴露坐骨神经。S1组和C1组分别于术前1h、术后1、2d时鞘内注射生理盐水5ul，E1组给予EphB受体拮抗剂EphB1与IgG的重组体（EphB1-Fc）0．5／ug；s2组和C2组于术后5d时鞘内注射生理盐水5ul，E2组给予EphB1-Fc0．5ug。各组分别于术前、术后1、3、5d时测定双侧热缩足潜伏期（PWL）和机械缩足阈值（PWT），计算非术侧与术侧PWL和PWT的差值（△PWL和△PWT）。于术后5d测定痛阈结束后，取术侧L4～6节段脊髓，采用免疫组织化学法检测c—Fos、P13K及磷酸化Akt（p-Akt）的表达水平。结果与S1组或S2组比较，C1组或C2组术后△PWL延长，△PWT增加，c—Fos、PI3K和p-Akt表达上调（P〈0．05）；与C1组或C2组比较，E组或E2组／xPWL缩短，△PWT降低，c—Fos、P13K和p-Akt表达下调（P〈0．05）。结论EphB受体通过P13K／Akt信号转导通路介导大鼠神经病理性痛的形成和维持。Objective To investigate the role of phosphatidylinositol 3-kinase （PI3K）/protein-serine-thre- onine kinases（Akt） signal transduction pathway in EphB receptor-mediated neuropathic pain in rats. Methods Forty-eight pathogen-free male SD rats aged 2-3 months weighing 150-180 g were randomly divided into 6 groups （n = 8 each）： groups sham operation （groups S1 and S2 ）; groups chronic constrictive injury （CCI） （groups C1 and C2 ） and groups EphB1-Fc （EphB receptor antagonist） ＋ CCI （groups E1 and E2 ）. Neuropathic pain was induced by placing 4 ligatures on left sciatic nerve at 1 mm intervals with 5-0 silk thread in groups C1, C2, E1 and E2 . EphB1-Fc 0.5 ug in 5 ul normal saline was injected intrathecally 1 h before operation and at 1 and 2 d after operation （group E1 ） or on 5th day after operation （group E2 ）. Normal saline 5 ul was injected intrathecally instead of EphB1-Fc 1 h before operation and at 1 and 2 days after operation （groups S1 and C1 ） or on 5th day after operation （groups S2 and C2 ）. Pain withdrawal latency to noxious thermal stimulation （PWL） and pain withdrawal threshold to noxious mechanical stimulation （PWT） were measured before operation and at 1, 3 and 5 d after operation. The animals were sacrificed at 5 d after operation after measurement of pain threshold. The lumbar segment of spinal cord （L4-6 ） was removed for determination of c-Fos, PI3K and phosphorylated Akt（p-Akt） expression. Results CCI significantly reduced PWL and PWT and up-regulated spinal c-Fos, PI3K and p-Akt expression in groups C1 and C2 as compared with groups S1 and S2 . EphB1-Fc significantly decreased hyperalgesia and the upregulated spinal Fos, PI3K and p-Akt protein expression induced by CCI in groups E1 and E2 as compared with groups C1 and C2. Conclusion Spinal EphB receptor is involved in the development and maintenance of neuropathic pain through PI3K/Akt signal transduction pathway.

关 键 词：1-磷脂酰肌醇3-激酶 蛋白质丝氨酸苏氨酸激酶 受体 Eph家族 神经痛 

分 类 号：R741[医药卫生—神经病学与精神病学]