CAJ | 학술논문

目的探讨脊髓Toll样受体4(TLR4)在大鼠持续性术后痛中的作用.方法雄性SD大鼠96只,体重200～250 g,采用随机数字表法,将其随机分为4组(n=24):假手术组(Ⅰ组)、持续性术后痛模型组(Ⅱ组)、SMIR+鞘内阴性对照siRNA组(Ⅲ组)和SMIR+鞘内TLR4siRNA组(Ⅳ组).采用Flatters法建立大鼠持续性术后痛模型,Ⅰ组和Ⅱ组于术前1d和术后1～6d鞘内注射人工脑脊液20μl,1次/d；Ⅲ组和Ⅳ组于术前1d和术后1～6d分别鞘内注射scramble siRNA 10 μl+人工脑脊液10μ1和TLR4siRNA 10μl+人工脑脊液10μl,1次/d.于术前1d,术后1、3、7、12、22 d时测定机械性痛阈(MWT),采用Western blot法测定脊髓TLR4蛋白表达.结果与Ⅰ组比较,Ⅱ组和Ⅲ组术后3、7、12、22 d时MWT降低,Ⅱ组和Ⅳ组术后3、7、12d时MWT降低,Ⅱ组和Ⅲ组术后3、7、12d时脊髓TLR4蛋白表达上调(P＜0.05)；与Ⅱ组比较,Ⅳ组术后3、7、12d时MWT升高,脊髓TLR4蛋白表达下调(P＜0.05).结论脊髓TLR4参与了大鼠持续性术后痛的形成.
목적 탐토척수Toll양수체4(TLR4)재대서지속성술후통중적작용.방법 웅성SD대서96지,체중200～250 g,채용수궤수자표법,장기수궤분위4조(n=24):가수술조(Ⅰ조)、지속성술후통모형조(Ⅱ조)、SMIR+초내음성대조siRNA조(Ⅲ조)화SMIR+초내TLR4siRNA조(Ⅳ조).채용Flatters법건립대서지속성술후통모형,Ⅰ조화Ⅱ조우술전1d화술후1～6d초내주사인공뇌척액20μl,1차/d；Ⅲ조화Ⅳ조우술전1d화술후1～6d분별초내주사scramble siRNA 10 μl+인공뇌척액10μ1화TLR4siRNA 10μl+인공뇌척액10μl,1차/d.우술전1d,술후1、3、7、12、22 d시측정궤계성통역(MWT),채용Western blot법측정척수TLR4단백표체.결과 여Ⅰ조비교,Ⅱ조화Ⅲ조술후3、7、12、22 d시MWT강저,Ⅱ조화Ⅳ조술후3、7、12d시MWT강저,Ⅱ조화Ⅲ조술후3、7、12d시척수TLR4단백표체상조(P＜0.05)；여Ⅱ조비교,Ⅳ조술후3、7、12d시MWT승고,척수TLR4단백표체하조(P＜0.05).결론 척수TLR4삼여료대서지속성술후통적형성.
Objective To investigate the role of Toll-like receptor4 (TLR4) activation in spinal cord in a rat model of persistent postoperative pain evoked by skin/muscle incision and retraction(SMIR).Methods Ninetysix male SD rats weighing 200-250 g were randomly divided into 4 groups(n =24 each):group sham operation; group SMIR; group SMIR + IT scramble siRNA and group SMIR + IT TLR4siRNA.The rat model of persistent postoperative pain evoked by SMIR was established according to the method described by Flatters.The TLR4 siRNA were administered intrathecally for 7 days starting from 1 day beforc surgcry.Pain behavior was assessed by paw mechanical withdraw threshold (MWT) to Electronic von Frey Anesthesiometer stimulation at 1 day before and 1,3,7,12,and 22 days after operation.Four animals were sacrificed at each time point in each group for detection of the expression of TLR4 protein in the spinal cord by Western blot analysis.Results Compared to group sham group,MWT was significantly descreased at 3,7,12,and 22 days after operation,while the expression of TLR4 protein in the spinal cord were significantly increased at 3,7,12 days after operation in group SMIR and group SMIR + IT scramble siRNA ; IT TLR4siRNA significantly attenuated the hyperalgesia induced by SMIR and descreased the expression of TLR4 protein at 3,7,12 days after operation in group SMIR + IT TLR4siRNA.Conclusion TLR4 activation in spinal cord plays an important role in the development of SMIR-evoked persistent postoperative pain in rats.