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

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250~280g,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1ml,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%O_2)麻醉下接受单次腹腔注射RTX 210μg/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60min和建模后每天鞘内注射等容量溶于DMSO的TSA 0.5μg/kg,持续到建模后7天。于建模前60min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-βmRNA,TNF-αmRNA和GFAP mRNA表达量明显增多(P<0.05)。与RTX和DMSO组比较,TSA组IL-1βmRNA、TNF-αmRNA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。

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 Thirtytwo 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 210μg/kg under isoflurane（2% O2）anesthesia;apathological neuralgia model was established in group DMSO via intrathecal injection of 10μl of 5% DMSO for 60 min before modeling and 7 dafter modeling.The TSA group established a pathological neuralgia model via injection intrathecal of TSA（0.5μg/kg）for 60 minutes before modeling and 7 dafter modeling.Mechanical withdrwal threshod（MWT）was quantified with von Frey filaments before and after modeling;the measurement time after the modeling was2 hafter intrathecal injection on the day of 1,3,5,7 d.The expression of glial fibrillary acidic protein（GFAP）,IL-1β,TNF-αmRNA in the spinal cord were measured by qRT-PCR 2 hafter last TSA or DMSO injection.Results Compared with group C,MWT in groups RTX,DMSO and TSA decreased significantly 3,5 and 7 dafter modeling（P〈0.05）.Compared with groups RTX and DMSO,MWT increased significantly 3,5 and 7 dafter 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-βmRNA,TNF-αmRNA and GFAP mRNA in groups RTX,DMSO and TSA increased significantly（P〈0.05）.Compared with groups RTX and DMSO,the expression of IL-1βmRNA and TNF-αmRNA 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.