延胡索乙素对小鼠坐骨神经CCI模型背根神经节Cav1.2表达的影响  

Effect of tetrahydropalmatine on expression of Cav1.2 in dorsal root ganglion neurons in mice with sciatic nerve chronic constriction injury

作　　者：姜海波[1] 王军[2] 苏建华[3] 房铭铭 杨楠[1] 杨家伟[1] 万芬[1] 肖杭[2] 唐金荣[1] 

机构地区：[1]南京医科大学第一附属医院神经内科,江苏南京210029 [2]南京医科大学公共卫生学院神经毒理系,江苏南京211100 [3]江苏大学附属金坛市人民医院神经内科,江苏金坛213200 [4]江苏省中西医结合医院神经内科,江苏南京210028

出　　处：《中国药理学通报》2015年第11期1598-1603,共6页Chinese Pharmacological Bulletin

基　　金：江苏省自然科学基金资助项目(No BK 2001116);江苏省常州市卫生局项目(No 2004-182-01)

摘　　要：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45mg·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。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&nbsp;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&nbsp;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

关 键 词：延胡索乙素 Cav1.2 坐骨神经慢性压迫性损伤 神经病理性疼痛 背根神经节 小鼠 

分 类 号：R-332[医药卫生] R284.1