CAJ | 학술논문

目的：探讨延胡索乙素对小鼠坐骨神经慢性压迫性损伤( CCI)所致神经病理性疼痛的镇痛作用以及对背根神经节Cav1.2表达的影响。方法♂ C57BL/6小鼠40只,随机分为5组,分别为假手术组( S组)、CCI组( C组)、延胡索乙素组(L组)。建立稳定的小鼠坐骨神经慢性压迫性损伤致神经病理性疼痛模型。按照神经病理性疼痛的诱发和持续时间,又将L组分为诱导期组、诱导维持期组、长程低剂量组。诱导期组于疼痛诱导期(0~5 d)、诱导维持期组于疼痛诱导期及维持期(0~5 d、14~19 d)腹腔给予延胡索乙素45 mg·kg-1,每日1次；长程低剂量组从术后即刻开始腹腔给予延胡索乙素15 mg·kg-1,每日1次,给予19 d。监测小鼠行为学变化,检测小鼠机械痛阈和热痛阈,Western blot及免疫组织化学方法测定背根神经节中Cav1.2表达。结果脊髓背根神经节Cav1.2在C组表达水平最低,S组表达水平最高,在诱导期组、诱导维持期组及长程低剂量组表达明显上调,差异具有统计学意义(P<0．05,P<0．01)。与C组比较,诱导期组、诱导维持期组高剂量以及长程低剂量组长程低剂量给予延胡索乙素可以明显缓解神经病理性疼痛诱导的机械痛敏和热痛敏(P<0．05,P<0．01)。高剂量延胡索乙素可以缓解诱导期、维持期的机械痛敏及维持期的热痛敏(P<0．05),低剂量延胡索乙素对诱导期机械痛敏和热痛敏均无明显作用( P>0．05)。结论小鼠CCI模型疼痛的诱导期、诱导维持期应用高剂量以及长程应用低剂量延胡索乙素可明显缓解坐骨神经慢性压迫性损伤所致神经病理性疼痛,其可能机制之一是延胡索乙素通过上调脊髓背根经节Cav1.2亚基的表达来发挥镇痛作用。
목적：탐토연호색을소대소서좌골신경만성압박성손상( CCI)소치신경병이성동통적진통작용이급대배근신경절Cav1.2표체적영향。방법♂ C57BL/6소서40지,수궤분위5조,분별위가수술조( S조)、CCI조( C조)、연호색을소조(L조)。건립은정적소서좌골신경만성압박성손상치신경병이성동통모형。안조신경병이성동통적유발화지속시간,우장L조분위유도기조、유도유지기조、장정저제량조。유도기조우동통유도기(0~5 d)、유도유지기조우동통유도기급유지기(0~5 d、14~19 d)복강급여연호색을소45 mg·kg-1,매일1차；장정저제량조종술후즉각개시복강급여연호색을소15 mg·kg-1,매일1차,급여19 d。감측소서행위학변화,검측소서궤계통역화열통역,Western blot급면역조직화학방법측정배근신경절중Cav1.2표체。결과척수배근신경절Cav1.2재C조표체수평최저,S조표체수평최고,재유도기조、유도유지기조급장정저제량조표체명현상조,차이구유통계학의의(P<0．05,P<0．01)。여C조비교,유도기조、유도유지기조고제량이급장정저제량조장정저제량급여연호색을소가이명현완해신경병이성동통유도적궤계통민화열통민(P<0．05,P<0．01)。고제량연호색을소가이완해유도기、유지기적궤계통민급유지기적열통민(P<0．05),저제량연호색을소대유도기궤계통민화열통민균무명현작용( P>0．05)。결론소서CCI모형동통적유도기、유도유지기응용고제량이급장정응용저제량연호색을소가명현완해좌골신경만성압박성손상소치신경병이성동통,기가능궤제지일시연호색을소통과상조척수배근경절Cav1.2아기적표체래발휘진통작용。
Aim To investigate the analgesic effect of tetrahydropalmatine on Cav1 . 2 expression in the dorsal root ganglion ( DRG) of mice with sciatic nerve chronic constriction injury ( CCI ) -induced neuropathic pain. Methods Forty male C57 BL/6 mice were randomly divided into 5 groups ( n =5 ): sham group ( group S) , CCI group ( group C ) and L-THP group ( group L) . Steady mice models of neuropathic pain were es-tablished by inducing CCI of sciatic nerve. According to development of neuropathic pain in mice, L group was divided into induction period, induction with ma-intenance period and long-term low-dose group. The mice were intraperitoneally administered with 45 mg · kg-1 tetrahydropalmatine in induction ( day 0~5 ) , in-duction with maintenance ( day 0~5 , 14~19 ) period of neuropathic pain state. From the instant after opera-tion, 15 mg · kg-1 tetrahydropalmatine was injected into the long-term low-dose group once per day for 19 days. Then, the behavior changes of mice were moni-tored. Moreover, the threshold of mechanical and ther-mal stimuli was tested. In addition, the expression of Cav1 . 2 protein was detected by Western blot and im-munohistochemical staining. Results The lowest ex-pression of Cav1 . 2 was observed in group C and the highest expression level of Cav1 . 2 was found in group S. Cav1. 2 expression was significantly up-regulated in induction period group, induction with maintenance period group and long-term low-dose group ( P<0. 05 , P<0. 01). Compared with group C, high dose of tet-rahydropalmatine in induction period group, induction with maintenance period group and long-term low-dose group showed reduced mechanical allodynia and ther-mal hyperalgesia induced by nerve injury ( P <0. 05 , P<0. 01). Meanwhile, high dose of tetrahydropalma-tine significantly relieved the mechanical allodynia in induction period group, induction with maintenance period group and thermal hyperalgesia in maintenance period group (P<0. 05). However, there was no ob-vious effect on mechanical allodynia and thermal hyper-algesia induced by nerve injury ( P >0. 05 ) in long-term low-dose group. Conclusions High dose of tet-rahydropalmatine in induction period group, induction with maintenance period group and low-dose among the whole experiment process obviously relieves the neuro-pathic pain induced by nerve injury. The analgesic effect of tetrahydropalmatine on neuropathic pain may be due to the increased expression of Cav1 . 2 protein in DRG neurons.