摘要
目的评价组蛋白去乙酰化酶6(HDAC6)在大鼠神经病理性痛维持中的作用及其与髓样分化因子88(MyD88)/NF-κB信号通路的关系。方法清洁级健康雄性SD大鼠24只,6~8周龄,体重200~260 g,采用随机数字表法分为4组(n=6):对照组(C组)、假手术组(S组)、神经病理性痛组(NP组)和NP+HDAC6抑制剂ACY-1215组(NP+ACY组)。采用结扎L5脊神经的方法制备大鼠神经病理性痛模型。S组仅暴露L5脊神经,不结扎;NP+ACY组于模型制备结束后,每日腹腔注射ACY-121525 mg/kg,至21 d;S组和NP组腹腔注射等体积溶剂,C组正常饲养。于模型制备前3 d(T0)、模型制备前当日(T1)、制备后1、3、7、10、14和21 d(T2~7)时测定大鼠后足机械缩足反应阈(MWT)。结扎脊神经后第21天测定MWT后处死大鼠取L4~6脊髓背角组织,采用Western blot法检测MyD88、NF-κB和p-NF-κB表达,RT-PCR法检测脊髓背角IL-1β和TNF-αmRNA表达。结果与C组和S组比较,NP组和NP+ACY组T2~7时MWT降低,脊髓背角MyD88、NF-κB、p-NF-κB、TNF-αmRNA和IL-1βmRNA表达上调(P<0.05);与NP组比较,NP+ACY组T5~7时MWT升高,脊髓背角MyD88、NF-κB、p-NF-κB、TNF-αmRNA和IL-1βmRNA表达下调(P<0.05)。结论HDAC6激活参与了大鼠神经病理性痛的维持,与激活MyD88/NF-κB信号通路有关。
Objective To evaluate the role of histone deacetylase 6(HDAC6)in the maintanence of neuropathic pain(NP)and the relationship with myeloid differentiation factor 88(MyD88)/nuclear factor kappa B(NF-κB)signaling pathway in the rats.Methods Twenty-four clean-grade healthy male Sprague-Dawley rats,aged 6-8 weeks,weighing 200-260 g,were divided into 4 groups(n=6 each)using a random number table method:control group(group C),sham operation group(group S),NP group and NP plus HDAC6 inhibitor ACY-1215 group(group NP+ACY).The rat model of NP was established by ligating the L5 spinal nerve in anesthetized rats.The L5 spinal nerve was only exposed without ligation in group S.In NP+ACY group,ACY-121525 mg/kg was intraperitoneally injected daily for 21 days after the end of model establishing.The equal volume of solvent was intraperitoneally injected in S and NP groups,and group C was reared normally.The mechanical paw withdrawal threshold(MWT)was measured on 3 days before establishing the model(T0),the day before establishing the model(T1)and 1,3,7,10,14 and 21 days after establishing the model(T2-7).The rats were sacrificed after measurement of MWT on day 21 after ligation,and the spinal dorsal horn tissues of L4-6 were removed for determination of the expression of MyD88,NF-κB and phosphorylated NF-κB(p-NF-κB)(by Western blot)and expression of interleukin-1beta(IL-1β)and tumor necrosis factor-alpha(TNF-α)mRNA(by real-time polymerase chain reaction).Results Compared with C and S groups,the MWT was significantly decreased at T2-7,and the expression of MyD88,NF-κB,p-NF-κB,TNF-α mRNA and IL-1β mRNA was up-regulated in NP and NP+ACY groups(P<0.05).Compared with group NP,the MWT was significantly increased at T5-7,and the expression of MyD88,NF-κB,p-NF-κB,TNF-α mRNA and IL-1β mRNA was down-regulated in group SNL+ACY(P<0.05).Conclusion HDAC6 activation is involved in the maintanence of NP,which is related to activating MyD88/NF-κB signaling pathway in the rats.
作者
陈春意
李靖凡
罗兰
国奥
冯晓波
刘安鹏
柯剑娟
Chen Chunyi;Li Jingfan;Luo Lan;Guo Ao;Feng Xiaobo;Liu Anpeng;Ke Jianjuan(Department of Anesthesiology,Zhongnan Hospital,Wuhan University,Wuhan 430071,China)
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2020年第8期988-991,共4页
Chinese Journal of Anesthesiology
基金
湖北省卫生计生科研基金(WJ2017M036)
武汉大学中南医院科技创新培育基金(znpy2018103)。
