鞘内注射Akt特异性抑制剂GSK690693抑制骨癌诱导的大鼠痛相关行为的研究

目的:探讨在大鼠乳腺癌骨转移诱导癌症疼痛的调控过程中Akt信号通路的作用。方法:将Wistar成模wistar大鼠随机分为Model组、Model+GSK690693组及Model+Saline组;Model组大鼠不进行鞘内注射,Model+GSK690693组及Model+Saline组大鼠,于手术后数天(post-cancer cell implantation day,PID)PID 13 d、14 d及21 d鞘内分别注入Akt特异抑制剂GSK690693、等量生理盐水组,分别于PID 0 d、7 d、14 d及21 d,观察大鼠痛相关行为学检查,PID 21 d取DRG行免疫印迹检查p-Akt表达。结果:在鞘内注射Akt特异性抑制剂GSK690693后,Model+GSK690693组大鼠的机械缩足反射阈值上升,自发性疼痛行为值及患侧DRG中p-Akt表达下降。在PID 14 d、21 d等不同时间节点,Model+GSK690693组大鼠的疼痛行为学与Model+Saline组大鼠、Model组大鼠经统计学比较有显著的统计学差异(P0.01);PID 21d Model+GSK690693组大鼠患侧DRG中p-Akt表达与Model组的比较有显著统计学意义(P0.01),与Model+Saline组比较有统计学意义(P0.05);结论:鞘内注射Akt特异性抑制剂GSK690693可抑制大鼠乳腺癌骨转移诱导的大鼠痛相关行为。

Research on the Inhibition of Breast Cancer Bone Metastasis Induced Rat Pain-related Behaviors by Intrathecally Injection of GSK690693, an Akt Specific Inhibitor

ABSTRACT Objective: To investigate the role of Akt signaling pathway in the regulation of breast cancer bone metastasis induced pain behavior in rat. Methods: Model rats were randomly divided into three groups: Model group, Model+GSK690693 group and Model+ Saline group. On PID 13, 14 and 21, Model+GSK690693 group rats were intrathecally injected with GSK690693, a specific inhibitor of Akt. Model+Saline group were injected with saline instead. The pain related behaviors were respectively recorded on PID 0, 7, 14 and 21. The expression of p-Akt in DRG used for western bloting were examed on PID 21. Results: After the injection of Akt specific inhibitor GSK690693 by intrathecal, In the Model+GSK690693 group, the threshold value of mechanical contraction reflex was increased, the spontaneous pain behavior and the expression of p-Akt in DRG decreased. On PID 14 d and 21 d, the pain behavior of rats in Mod- el+GSK690693 group was significantly different from that of Model+Saline group and Model group (P<0.01); On PID 21 d, There was significant statistical significance (P<0.01) on the expression of p-Akt and Model in the ipsilateral Model+GSK690693 of DRG group, which was statistically significant (P<0.05) compared with the Model+Saline group. Conclusion: Intrathecal injection of Akt specific in- hibitor GSK690693 inhibits rat pain related behaviors induced by bone metastasis in rat breast cancer.