CAJ | 학술논문

目的探讨鞘内注射TRESK基因重组腺病毒对神经病理性痛大鼠脊髓p38丝裂原活化蛋白激酶(p38MAPK)和细胞外信号调节蛋白激酶(ERK)活性的影响.方法健康雄性SD大鼠36只,体重200～ 250 g,采用随机数字表法,将其分为6组(n=6):空白对照组(C组)、假手术组(S组)、神经病理性痛组(NP组)、TRESK过表达腺病毒组(TRESK组)、阴性腺病毒组(Virus组)和生理盐水组(NS组).采用坐骨神经分支选择性损伤法制备神经病理性痛模型.TRESK组、NS组和Virus组于造模成功后即刻分别鞘内注射pAd/CMV/V5-DEST-TRESK 25 μl(109 IU/ml)、阴性腺病毒25μl和生理盐水25μl.于造模前1d和造模后1、3、7 d(T0-3)时测定机械缩足反应阈(MWT)和热缩足潜伏期(TWL).于造模后7d痛阈测定结束后,处死大鼠,取脊髓组织,采用Western blot法测定脊髓p38MAPK和ERK磷酸化水平.结果与C组比较,NP组、TRESK组、Virus组和NS组T1～3时MWT降低,脊髓p38MAPK和ERK磷酸化水平升高(P＜0.05).与NP组比较,TRESK组T1～3时MWT升高,脊髓p38MAPK和ERK磷酸化水平降低(P＜0.05),Virus组和NS组差异无统计学意义(P＞0.05).6组大鼠各时点TWL组间比较差异无统计学意义(P＞0.05).结论鞘内注射TRESK基因重组腺病毒减轻大鼠神经病理性痛的机制与可能与抑制脊髓p38MAPK和ERK的活性有关.
목적 탐토초내주사TRESK기인중조선병독대신경병이성통대서척수p38사렬원활화단백격매(p38MAPK)화세포외신호조절단백격매(ERK)활성적영향.방법 건강웅성SD대서36지,체중200～ 250 g,채용수궤수자표법,장기분위6조(n=6):공백대조조(C조)、가수술조(S조)、신경병이성통조(NP조)、TRESK과표체선병독조(TRESK조)、음성선병독조(Virus조)화생리염수조(NS조).채용좌골신경분지선택성손상법제비신경병이성통모형.TRESK조、NS조화Virus조우조모성공후즉각분별초내주사pAd/CMV/V5-DEST-TRESK 25 μl(109 IU/ml)、음성선병독25μl화생리염수25μl.우조모전1d화조모후1、3、7 d(T0-3)시측정궤계축족반응역(MWT)화열축족잠복기(TWL).우조모후7d통역측정결속후,처사대서,취척수조직,채용Western blot법측정척수p38MAPK화ERK린산화수평.결과 여C조비교,NP조、TRESK조、Virus조화NS조T1～3시MWT강저,척수p38MAPK화ERK린산화수평승고(P＜0.05).여NP조비교,TRESK조T1～3시MWT승고,척수p38MAPK화ERK린산화수평강저(P＜0.05),Virus조화NS조차이무통계학의의(P＞0.05).6조대서각시점TWL조간비교차이무통계학의의(P＞0.05).결론 초내주사TRESK기인중조선병독감경대서신경병이성통적궤제여가능여억제척수p38MAPK화ERK적활성유관.
Objective To evaluate the effects of intrathecal TRESK gene recombinant adenovirus on the expression of p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated kinase (ERK) in the spinal cord of rats with neuropathic pain.Methods Thirty-six male Sprague-Dawley rats,weighing 200-250 g,were randomly divided into 6 groups (n=6 each) using a random number table:control group (group C);sham operation group (group S);neuropathic pain group (group NP);TRESK overexpression adenovirus group (group TRESK);negative adenovirus group (group Virus);normal saline group (group NS).The rats underwent spared nerve injury (SNI) to establish the nodel of neuropathic pain.In TRESK,NS and Virus groups,pAd/CMV/V5-DEST-TRESK 25 μl (109 IU/ml),negative adenovirus 25 μl and normal saline 25 μl were intrathecally injected,respectively,immediately after SNI.At 1 day before SNI (baseline,T0) and 1,3 and 7 days after SNI (T1-3),the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.The rats were sacrificed after the last measurement of pain threshold at T3.The lumbar segments (L4,5) of the spinal cord were removed for determination of phosphorylation of p38MAPK and ERK by Western blot.Results Compared with group C,the MWT was significantly decreased at T1-3,and the phosphorylation of p38MAPK and ERK was increased in NP,TRESK,Virus and NS groups.Compared with group NP,the MWT was significantly increased at T1-3,and the phosphorylation of p38MAPK and ERK was decreased in group TRESK,and no significant change was found in phosphorylation of p38MAPK and ERK in Virus and NS groups.There was no significant difference in TWL between the six groups.Conclusion Inhibited activities of p38MAPK and ERK in the spinal cord may be involved in the mechanism by which intrathecal TRESK gene recombinant adenovirus alleviates neuropathic pain in rats.