氯胺酮对骨癌痛模型大鼠脊髓信号传导子与转录激活子STAT3表达的影响

Effects of intraperitoneal ketamine on the expression of signal transducers and activators of transcription 3 in the lumbar spinal cord induced by the tibial cancer pain in rats

目的 观察腹腔注射氯胺酮对骨癌痛模型大鼠腰段脊髓背角STAT3表达的影响。方法 选择成年雌性SD大鼠24只，体质量180—220g，随机分为4组（n=6）：A组（对照组）：左侧胫骨上段骨髓腔注入3μl Hank液；B组（模型组）：左侧胫骨上段骨髓腔注3-μl MADB-106大鼠乳腺癌细胞（4．8×10^9／L）；C组（氯胺酮10mg／kg体重）；D组（氯胺酮20mg／kg体重）；C，D二组造模同B组。从第14天开始，A，B组大鼠腹腔分别注射生理盐水1ml，C，D组大鼠腹腔分别注射氯胺酮10mg／kg体重（1ml）及20mg／kg体重（1ml），1次／d，连续4d。术前及术后1～22d，各组大鼠隔日观察辐射热痛阚值变化。第22天，取大鼠脊髓L4～6节段，采用免疫组织化学方法观察脊髓背角STAT3的表达。结果 A组大鼠对辐射热痛刺激的缩爪阈值在术后各时间点组内比较差异无统计学意义；术后14—22d，与A组大鼠对辐射热痛刺激缩爪阈值比较，B、C组差异有统计学意义（P〈0．05），而D组比较差异无统计学意义（P〉0．05）。大鼠腰脊髓背角Ⅰ—Ⅳ STAT3免疫反应吸光度值B、C组与A组比较差异有统计学意义（P〈0．05），D组与A组比较差异无统计学意义。结论 腹腔注射20mg／kg体重氯胺酮抑制了胫骨癌痛模型大鼠患侧腰段脊髓背角STAT3表达，NM-DA／STAT3信号通路的激活参与了骨癌痛的维持。

Objective To investigate the effects of repeated intraperitoneal administration of ketamine on signal transducers and activators of transcription 3 （ STAT3 ） in the lumbar spinal cord neurons induced by the tibial cancer pain in rats. Methods Twenty-four SD female rats weighing 180-220 g were randomly divided into 4 groups （ n = 6 each ） ： group A （ control group ） ： intra-tibial injection of 3 μl Hank＇ s solution; group B （model group） ：intra-tibial injection of 3 μMADB-106 mammary gland carcinoma ceils of rats （4.8×10^9 ceils/p./） ; group C （ketamine 10 mg/kg） ; group D （ketamine 20 mg/kg）, The procedures in groups C and D were the same as those in the group B. From the 14th day after operation, ketamine （ 10 mg/kg, 1 ml,or 20 mg/kg, 1 ml） was injected intraperitoneally into groups C and D respectively and normal saline （ 1 ml） was injected into groups A and B once every day for 4 days. Mechanical withdrawal thresholds and radiant heat threshold of rats＇ hind paws were measured every other day from one day before operation until 22 days later. The lumbar 4-6 spinal cord was removed on the 22nd day. The changes of the spinal STAT3 immunoreactivity were detected by immunohistochemistry SABC method. Results No significant differences in radiant heat threshold were found at all time points in group A. During the first 6 days after operation there were obvious differences in radiant heat stimulus between group A and the other groups （P 〈0.05） ; During 14-22 days after operation,mechanical pain threshold and radiant heat threshold in groups B and C were sign itlcantly dufferent from those in group A （ P 〈 0. 05 ）, but the differences were not remarkable between groups A and D. The STAT3 immunoreactivity in groups B and C in laminae ,Ⅰ -Ⅳ of dorsal hem showed stronger staining than in group A＇（ P 〈 0.05 ）, No significant difference in STAT3 imntunoreactivity was found between groups D and A （P 〉0. 05 ）. Conclusion Intraperitoneal injection of ketamine provides analgesia in the tibial cancer pain rats and inhibits the STAT3 expression in the lumbar spinal dorsal horn neurons, suggesting that activation of NMDA/STAT3 signal pathway is involved in the bone cancer pain.