鞘内注射赛庚啶缓解小鼠骨癌痛

目的: 观察鞘内注射SET domain containing lysine methyltransferase 7/9 (SET7/9)抑制剂赛庚啶对骨癌痛模型小鼠机械性痛觉过敏阈值(paw withdrawal mechanical threshold，PWMT)及脊髓背角SET7/9表达的影响。方法: 选择88只雄性C3H/HeJ小鼠，体质量20～25 g。实验分为2部分：第1部分实验将小鼠随机均分为假手术组及骨癌痛组，每组8只，观察两组小鼠术前1 d及术后5、7、12、15 d PWMT的变化；采用蛋白质印迹法检测两组小鼠(n=4)术前1 d及术后15 d脊髓背角SET7/9的表达。第2部分实验将小鼠随机分为假手术组、骨癌痛组、骨癌痛+赛庚啶 10 nmol组、骨癌痛+赛庚啶 20 nmol组、骨癌痛+ SET7/9 0.2 μg组、骨癌痛+SET7/9 0.2 μg+赛庚啶20 nmol组及骨癌痛+氯苯那敏 200 μg组，每组8只；观察鞘内给药前(0 h)及鞘内给药后1、3、6 h 各组PWMT的变化；蛋白质印迹法测定骨癌痛组(n=4)及骨癌痛+赛庚啶 20 nmol组(n=4)鞘内给药前(0 h)及鞘内给药后6 h脊髓背角SET7/9的表达。结果： 与假手术组相比，骨癌痛组小鼠术后7～15 d PWMT显著降低(P <0.05或0.01)，15 d脊髓背角SET7/9明显增加(P<0.01)。与骨癌痛组相比，骨癌痛+赛庚啶10 nmol组、骨癌痛+赛庚啶20 nmol组鞘内注射3 h后PWMT明显增加(P<0.05或0.01)，骨癌痛+赛庚啶20 nmol组小鼠脊髓背角SET7/9表达明显降低(P<0.01)。 结论： 鞘内注射赛庚啶可明显提高15 d骨癌痛小鼠PWMT及降低骨癌痛小鼠脊髓背角SET7/9的表达；脊髓SET7/9可能参与小鼠骨癌痛的发展过程。

Intrathecal injection of cyproheptadine ameliorates bone cancer pain in mice

Objective: To investigate the effects of intrathecal injection of cyproheptadine, an inhibitor of SET domain containing lysine methyltransferase 7/9(SET7/9), on paw withdrawal mechanical threshold (PWMT) and the expression of SET7/9 in spinal dorsal horn of bone cancer pain (BCP) mice. Methods: Eighty eight male C3H/HeJ mice were selected， weighing 20-25 g. The experiments divided into two parts. Part I, mice were randomly divided into sham and BCP groups. Established a mouse model of bone cancer pain, NCTC 2472 cancer cells were inoculated into the intramedullary space of the mice left femur. The changes of PWMT were measured at l d before operation and 5, 7, 12, 15 d after operation(n=8)， and the spinal expression of SET7/9 at l d before operation and 15 d after operation (n=4) was also observed. PartⅡ, mice were randomly divided into sham, BCP, BCP+cyproheptadine 10 nmol, BCP+cyproheptadine 20 nmol, BCP+SET7/9 0.2 μg, BCP+SET7/9 0.2 μg+cyproheptadine 20 nmol, BCP+ chlorpheniramine 200 μg groups. The changes of PWMT were measured at 0 h before and 6 h after intrathecal injection(n=8) were measured in all groups, and the expression of SET7/9 in the spinal dorsal horn was measured by western blot analysis at 0 h before and 6 h after intrathecal injection in BCP and BCP+cyproheptadine 20 nmol groups(n=4). Results: The PWMT was significantly reduced 7-15 d after inoculation of cancer cells(P<0.05 or 0.01), and the spinal SET7/9 was significantly increased 15 d after inoculation of cancer cells(P<0.01). Compared with BCP group, the PWMT was significantly increased 3 h after intrathecal in BCP+cyproheptadine 10 nmol group and BCP+cyproheptadine 20 nmol group. The expression of spinal SET7/9 was significantly decreased in BCP+cyproheptadine 20 nmol group. Conclusion: Intrathecal cyproheptadine could significantly increase PWMT and reduce the expression of SET7/9 in spinal dorsal injection of horn in 15 d BCP mice. Spinal SET7/9 may participate in the development of bone cancer pain in mice.