中文摘要：

目的评价CREB结合蛋白质（CBP）在神经病理性痛大鼠脊髓COX-2表达中的作用。方法雄性SD大鼠40只，体重220—250g，鞘内置管成功后5d时采用坐骨神经慢性缩窄性损伤的方法制备大鼠神经病理性痛模型，采用随机数字表法，将其随机分为4组（n=10）：假手术组（Sham组）、神经病理性痛组（NP组）、阴性对照病毒载体组（NC组）和CBP组。NC组和CBP组制备模型后7d时分别鞘内注射阴性对照病毒载体（RNAi-NC-LV）、CBPshRNA病毒载体（CBPRNAi-LV）20μl。于术前1d、术后3、5、7、10、12、14d时测定大鼠术侧机械缩足反应阈值（MWT）和热缩足潜伏期（TwL）。于术后14d时取腰段脊髓，免疫组化法检测CBP、乙酰化组蛋白H3／H4（Ac-H3，Ac-H4）、COX-2蛋白的表达，RT-PCR法检测CBP、COX．2mRNA的表达。结果与Sham组比较，NP组、NC组和CBP组大鼠术后各时点术侧MwT和TWL降低，NP组和NC组大鼠术后14d时脊髓CBP、Ac-H3、Ac—H4、COX．2蛋白表达和CBP、COX-2mRNA表达上调（P〈0．05），CBP组上述各指标差异无统计学意义（P〉0．05）；与NP组比较，CBP组术后lO、12和14d时MwT和聊L升高，术后14d时脊髓CBP、Ac—H3、Ac-H4、COX-2蛋白表达和CBP、COX-2mRNA表达下调（P〈0．05）。结论CBP表达上调导致组蛋白H3、H4乙酰化水平升高，脊髓神经元COX-2表达上调，参与了神经病理性痛的形成。

英文摘要：

Objective To evaluate the role of CREB-binding protein （CBP） in cyclooxygenase 2 （COX- 2） expression in spinal cord in a rat model of neuropathic pain （ NP）. Methods Forty male SD rats weighing 220- 250 g in which intrathecal catheter was successfully implanted were randomly divided into 4 groups （ n = 10 each） ： sham operation group （group Sham）, group NP, negative control group （group NC） and group CBP. NP was in- duced by CCI at 5 days after successful implantation of the intrathecal catheter. Normal saine, negative lentivirus vector （RNAi-NC-LV） and CBP shRNA lentivirus vector （CBP RNAi-LV） 20 μl were injected intrathecally at 7 days after CCI in groups NP, NC and CBP, respectively. Paw withdrawal threshold to mechanical stimuli （MWT） and paw withdrawal latency to thermal stimulus （TWL） were measured at 1 day before operation and at 3, 5, 7, I0, 12 and 14 days after operation. The rats were sacrificed after the measurement of MWT and TWL at 14 days after operation and the lumbar segment of the spinal cord was then removed for determination of the expression of CBP, acetylated histone H3/H4 （Ac-H3, Ac-H4） and COX-2 protein （by immunohistochemistry）, and CBP and COX-2 mRNA （by RT-PCR） .Results Compared with group Sham, MWT and TWL were significantly decreased at different time points after operation in groups NP, NC and CBP, and the expression of CBP, Ac-H3, Ac-H4 and COX-2 protein, and CBP and COX-2 mRNA was up-regulated at 14 days after operation in groups NP and NC （P 〈 0.05）. Compared with group NP, MWT and TWL were significantly increased at 10, 12 and 14 days after operation and the expression of CBP, Ac-H3, Ac-H4 and COX-2 protein, and CBP and COX-2 mRNA was down- regulated at 14 days after operation in group CBP （ P 〈 0.05）. Conclusion CBP is involved in the development of NP by up-regulating COX-2 expression and increasing histone H3 and H4 acetylation in spinal cord.