曲古抑菌素A通过抑制脊髓背角内的炎症反应减轻大鼠神经病理性痛

目的:观察曲古抑菌素A (TSA)对脊神经结扎(SNL)大鼠镇痛效果及分子机制。方法:40只健康雄性Sprague Dawley(SD)大鼠随机分为假手术组(sham)、曲古抑菌素A处理组(TSA)、脊神经结扎组(SNL)和SNL+TSA组(SNL+TSA)。采用L5脊神经结扎(SNL)的方法建立神经病理性痛模型,鞘内注射TSA进行干预,通过von Frey丝和热板实验检测大鼠的痛敏,应用免疫荧光染色方法观察大鼠脊髓背角内HDAC1的表达情况;应用Western Blot方法观察大鼠脊髓背角内胶质纤维酸性蛋白(GFAP)和离子钙接头蛋白分子1(Iba-1)的表达水平;应用real time RT-PCR方法检测大鼠脊髓背角内TNF-α、IL-1β和IL-6的mRNA表达水平。结果:SNL模型大鼠术后机械性痛阈值和热痛阈值均显著降低(P <0.05),鞘内给予TSA能够明显缓解大鼠患侧后足机械性痛敏和热痛敏;SNL模型大鼠脊髓背角内HDAC1的表达较对照组明显增加,而鞘内注射TSA可显著抑制其表达;SNL术后脊髓背角内GFAP和Iba-1的表达显著升高(P <0.05),鞘内给予TSA能够明显下调GFAP和Iba-1的表达;SNL术后大鼠脊髓背角内TNF-α、IL-1β和IL-6的表达较对照组明显上调(P <0.05),而鞘内给予TSA能够显著逆转这一趋势。结论:鞘内给予TSA能够通过抑制脊髓HDAC1表达缓解大鼠神经病理性痛。

Trichostatin A ameliorates neuropathic pain via inhibiting neuroinflammation in the spinal dorsal horn of rats

Objective: To observe the analgesic effect and molecular mechanism of trisostatin A(TSA) on spinal nerve ligation(SNL) rats.Methods: Forty healthy male Sprague Dawley(SD) rats were randomly divided into sham group(sham),trisostatin A treatment group(TSA),spinal nerve ligation group(SNL),and SNL + TSA group(SNL + TSA).Neuropathic pain model was prepared by left L5 spinal nerve ligation(SNL) in rats.Intrathecal injection of TSA was used for intervention in TSA group and SNL + TSA group.Hyperalgesia of rats was assessed by von Frey hair and hot plate test.The expression of HDAC1 in rat spinal dorsal horn was observed by immunofluorescent staining.The expression of glial fibrillary acidic protein(GFAP) and ionized calcium binding adaptor molecule-1(Iba-1) in spinal dorsal horn of rats were observed by Western Blot.The mRNA expression of TNF-α,IL-1β and IL-6 in the spinal dorsal horn of rats were measured by real time RT-PCR.Results: The paw withdrawal threshold(PWT) and paw withdrawal latency(PWL) were decreased when comparing with the sham group(P < 0.05),while the mechanical and thermal allodynia were significantly attenuated after intrathecal injection of TSA.The expression of HDAC1 in the spinal dorsal horn of SNL model rats was significantly increased compared with sham group,while intrathecal injection of TSA could significantly inhibit its expression.The expressions of GFAP and Iba-1 in the spinal dorsal horn were significantly increased after SNL surgery(P < 0.05).The expression of GFAP and Iba-1 could be significantly down-regulated by continuous intrasheath TSA on the 3 rd day after surgery.The expressions of TNF-α,IL-1β and IL-6 in the spinal dorsal horn were significantly upregulated after SNL surgery compared with the control group(P < 0.05),and intrasheath TSA could significantly reverse this trend.Conclusion: Intrathecal administration of TSA can alleviate neuropathic pain in rats by inhibiting HDAC1 expression of spinal cord.