己酮可可碱对神经病理性疼痛大鼠前扣带回皮质内BRD4 表达的影响

Effects of pentoxifylline on BRD4 expression in the anterior cingulate cortex of rats with neuropathic pain

目的:探讨己酮可可碱腹腔注射对神经病理性疼痛大鼠前扣带回皮质内嗅结构域蛋白4(BRD4)表达的影响。方法:神经病理性疼痛模型选择慢性坐骨神经压迫(CCI)模型大鼠。取正常健康雄性SD大鼠20只,随机分为正常组(N组)、假手术组(S组)、模型组(C组)及己酮可可碱治疗组(P组)4组,每组5只。于术后14 d处死所有大鼠,取前扣带回皮质。造模后记录大鼠痛阈变化并在取材前进行旷场实验观察疼痛引起的大鼠焦虑表现,ELISA测定各组前扣带回皮质内肿瘤坏死因子α(TNF-α)的含量,Western blot测定BRD4表达变化。结果:与N、S组相比,C组大鼠造模后机械缩足阈值及热缩足潜伏期下降(P<0.01),前扣带回皮质内TNF-α和BRD4表达增多(P<0.05),且有焦虑表现;P组大鼠与C组大鼠相比,机械缩足阈值和热缩足潜伏期升高(P<0.05),前扣带回皮质内TNF-α及BRD4表达减少(P<0.05),且大鼠焦虑改善。结论:神经病理性疼痛大鼠痛阈下降,有焦虑表现,前扣带回皮质内BRD4表达增多。己酮可可碱腹腔注射可减轻模型组大鼠痛觉过敏,抑制神经病理性疼痛大鼠前扣带回皮质内BRD4的表达,改善疼痛引起的焦虑表现。

Objective:To investigate the effects of intra-peritoneal injection of pentoxifylline on bromodomain-containing protein 4(BRD4)expression in the anterior cingulate cortex and anxiety in rats of neuropathic pain.Methods:Rat models of neuropathic pain were established using chronic constriction injury(CCI).Twenty healthy male SD rats were randomly divided into normal group(Group N,n=5),sham operation group(Group S,n=5),model group(Group C,n=5)and pentoxifylline treatment group(Group P,n=5).After modeling,the change of pain threshold was recorded and anxiety behavior of rats induced by pain was observed via open field experiment before sampling.All rats were sacrificed at day 14 after model establishment to obtain the anterior cingulate cortices,in which the content of TNF-α and BRD4 expression was measured respectively by ELISA and Western blot.Results:Mechanical withdrawal threshold and paw withdrawal latency were significantly decreased in rats in group C(P<0.01),with evidently up-regulated expression of TNF-α and BRD4 in the anterior cingulate corticesand showed anxiety behavior(P<0.05).Compared with group C,the mechanical withdrawal threshold and paw withdrawal latency were significantly increased(P<0.05),whereas the expression of TNF-αand BRD4 was markedly decreased in the anterior cingulate cortex,and the anxiety was alleviated in rats of group P.(P<0.05).Conclusion:Decreased pain threshold with anxiety and up-regulated BRD4 expression in the anterior cingulate cortex are observed in rats of neuropathic pain,and intra-peritoneal injection of pentoxifylline could relieve hyperalgesia,inhibit BRD4 expression in the anterior cingulate cortex and improve the anxiety induced by pain in model rats.