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| 鞘内注射曲古菌素A对树胶脂毒素诱导的大鼠神经痛的影响 |
| Effect of intrathecal injection trichostatin A in a rat model of resiniferatoxin induced neuropathic pain |
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| DOI：10.12089/jca.2018.06.014 |
| 中文关键词: 曲古菌素A 树胶脂毒素 神经病理性痛 星形胶质细胞 白细胞介素-1β, 肿瘤坏死因子-α |
| 英文关键词: Trichostatin A Resiniferatoxin Postherpetic neuralgia Glial fibrillary acidic protein IL-1β TNF-α |
| 基金项目:国家自然科学基金(81471136) |
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| 中文摘要: |
目的 评价曲古菌素A(trichostatin A, TSA)在树胶脂毒素(resiniferatoxin, RTX)诱导的神经病理性疼痛模型(模拟PHN)中的作用。
方法 雄性健康SD大鼠32只, 体重250～280 g, 采用随机数字表法分成四组: 溶媒对照组(C组)、神经痛模型组(RTX组)、二甲基亚砜(Dimethyl sulfoxide)治疗组(DMSO组)和TSA治疗组(TSA组)。C组单次腹腔注射RTX溶剂1 ml, RTX组建立病理性神经痛模型, 建模方式为每只大鼠在异氟醚(2%O2)麻醉下接受单次腹腔注射RTX 210 μg/kg;DMSO组建立病理性神经痛模型, 在建模前60 min和建模后每天鞘内注射TSA溶媒5% DMSO 10μl, 持续至建模后7天;TSA组建立病理性神经痛模型, 在建模前60 min和建模后每天鞘内注射等容量溶于DMSO的TSA 0.5 μg/kg, 持续到建模后7天。于建模前60 min和建模后第1、3、5和7天采用一系列校准的von Frey毛针测定四组大鼠机械痛阈值(MWT), 于第7天行为学测定结束后检测脊髓IL-1β、 TNF-α和胶质纤维酸性蛋白（GFAP）等分子mRNA表达量。
结果 与C组比较, 建模后第3、5和7天RTX、DMSO和TSA组MWT明显降低(P<0.05)。与RTX和DMSO组比较, 建模后第3、5和7天TSA组MWT明显升高(P<0.05)。RTX和DMSO组不同时点MWT差异无统计学意义。与C组比较, RTX、DMSO和TSA组IL1-β mRNA, TNF-α mRNA和GFAP mRNA表达量明显增多(P<0.05)。与RTX和DMSO组比较, TSA组IL-1β mRNA、 TNF-α mRNA表达量明显减少(P<0.05)。RTX和DMSO组各指标差异无统计学意义。
结论 鞘内注射TSA通过减缓脊髓炎性反应缓解RTX诱导的神经病理性痛。 |
| 英文摘要: |
Objective To study the effect of intrathecal injection trichostatin A (TSA) in a rat model of resiniferatoxin (RTX) induced neuropathic pain (a PHN mimic model).
Methods Thirty-two male SD rats, weighing 250-280 g, were randomly divided into four groups (n = 8): sham group (group C); neuropathic pain group (group RTX); intrathecal injection DMSO in neuropathic pain rats (group DMSO); intrathecal injection TSA in neuropathic pain rats (group TSA). In group C, 1 ml of RTX solvent was injected intraperitoneally. The pathological neuralgia model was established in RTX group. Each rat was given a single intraperitoneal injection of RTX 210 μg/kg under isoflurane (2% O2) anesthesia; a pathological neuralgia model was established in group DMSO via intrathecal injection of 10 μl of 5% DMSO for 60 min before modeling and 7 d after modeling. The TSA group established a pathological neuralgia model via injection intrathecal of TSA (0.5 μg/kg) for 60 minutes before modeling and 7 d after modeling. Mechanical withdrwal threshod (MWT) was quantified with von Frey filaments before and after modeling; the measurement time after the modeling was 2 h after intrathecal injection on the day of 1, 3, 5, 7 d. The expression of glial fibrillary acidic protein (GFAP), IL-1β, TNF-α mRNA in the spinal cord were measured by qRT-PCR 2 h after last TSA or DMSO injection.
Results Compared with group C, MWT in groups RTX, DMSO and TSA decreased significantly 3, 5 and 7 d after modeling (P < 0.05). Compared with groups RTX and DMSO, MWT increased significantly 3, 5 and 7 d after modeling (P < 0.05). There was no significant difference in MWT between group RTX and group DMSO at different time points. Compared with group C, the expressions of IL1-β mRNA, TNF-α mRNA and GFAP mRNA in groups RTX, DMSO and TSA increased significantly (P < 0.05). Compared with groups RTX and DMSO, the expression of IL-1β mRNA and TNF-α mRNA decreased significantly in group TSA (P < 0.05). There was no significant difference in the indexes between group RTX and group DMSO.
Conclusion Intrathecal injection of TSA relieves RTX-induced neuralgia by slowing the inflammatory response of the myocardium. |
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