鞘内注射LY294002对保留性脊神经损伤大鼠脊髓中PI3K和pERK信号的影响

目的：观察保留性脊神经损伤（SNI）大鼠鞘内注射LY294002能否通过抑制脊髓中磷脂酰肌醇‐3‐激酶PI3K ，进而影响pERK信号而缓解神经病理性疼痛。方法24只雄性 SD大鼠随机分为4组，即假手术（Sham）组、SNI组、SNI＋二甲基亚砜（DMSO）组及 SNI＋ LY294002（PI3K 抑制剂）组，每组6只，其中 SNI＋LY294002组和SNI＋DMSO组分别于SNI后第5天经鞘内注射LY294002和等体积DMSO ，每天1次，直到SNI后第14天。SNI前和SNI后1，3，5，7，10，14 d ，测定大鼠机械刺激缩足反应阈值（PWM T ）和热辐射刺激缩足反应潜伏期（PWTL）。SNI后第14天，大鼠麻醉后取腰段脊髓行Western‐blot检测PI3K和pERK的表达。结果与Sham组比较，SNI后各时点SNI组大鼠的 PWMT 和PWTL 均下降，脊髓中PI3K和 pERK表达则显著增强（P＜0．05）。与SNI组和SNI＋DMSO组比较，SNI后各时点SNI＋LY294002组大鼠的PWMT和PWTL均显著增高（P＜0．05），PI3K和pERK的表达则下降（P＜0．05）。结论经鞘内注射LY294002可抑制脊髓中PI3K ，进而影响pERK信号而缓解SNI大鼠神经病理性疼痛。

Intrathecal LY294002 Injection Inhibits Spinal PI3K andpERK Induced by SNI in Rats

Objective To observe whether intrathecal LY294002 injection could inhibit PI3K‐pERK to alleviate neuropathic pain induced by SNI in rats . Methods 24 adult male rats of Sprague Daw‐ley (SD) were randomly divided into four groups :Sham ,SNI (spared nerve injury) ,SNI+ DMSO and SNI+LY294002 (n= 6) . Rats in SNI+ LY294002 group and SNI+ DMSO group received intrathecal LY294002(PI3K inhibitor) and DMSO daily from day 5 to day 14 after SNI ,respectively . Paw with‐drawal mechanical thresholds (PWMT) and paw withdrawal thermal latency (PWTL) were measured on the 1st day before SNI and 1 ,3 ,5 ,7 ,10 and 14 days after SNI . On day 14 after SNI ,all rats were kill‐ed under deep anesthesia ,and their lumbar spinal cords were dissected to detect the levels of PI3K and pERK with western blot analysis (n=6) . Results Compared with those in Sham group ,the PWM T and PWTL in SNI group were all decreased ,whereas the PI3K and pERK levels were increased on day 14 after SNI(P<0 .05) . Compared with those in SNI and SNI+DMSO group after SNI ,the PWM T and PWTL in SNI+ LY294002 group were all up‐regulated (P< 0 .05) ,however ,the PI3K and pERK levels were down‐regulated on day 14 after SNI (P<0 .05) ,which indicated that LY294002 relieved mechanical allo‐dynia and thermal hyperalgesia induced by SNI . Conclusions The results from this study show that in‐trathecal LY294002(PI3K inhibitors) inhibits PI3K and pERK ,therefore it can alleviate neuropathic pain induced by SNI in rats .