盐酸布桂嗪对神经病理性疼痛模型小鼠痛行为及前扣带回小窝蛋白1表达的影响  

The effects of Bucinnazine Hydrochloride on the pain behavior and expression of caveolin-1 in anteri- or eingulate cortex of neuropathic pain mice

作　　者：杨俊霞 姜彦羽 花璐 李燕强 

机构地区：[1]徐州医科大学江苏省麻醉学重点实验室,江苏省麻醉与镇痛应用技术重点实验室,徐州221000 [2]徐州医科大学江苏省麻醉学重点实验室附属医院麻醉科,徐州221000 [3]华中科技大学同济医学院附属同济医院麻醉科,武汉430030

出　　处：《中华行为医学与脑科学杂志》2017年第11期967-971,共5页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金项目（81500950）

摘　　要：目的采用慢性坐骨神经结扎（chronicconstrictioninjury，CCI）小鼠模型，探讨盐酸布桂嗪对神经病理性疼痛模型小鼠痛行为及前扣带回（anteriorcingulatecortex，ACC）小窝蛋白1（Caveo-lin-1，Cav-1）表达的影响。方法将20～25g的成年雄性昆明小鼠64只按完全随机分组法分为4组（每组16只）：Sham＋BH（BucinnazineHydrochloride，盐酸布桂嗪）组、Sham＋NS（normalsaline，生理盐水）组、CCI＋BH组、CCI＋NS组。从CCI第4天开始腹腔注射相应药物，每天1次，连续给药3d。热辐射刺激仪检测小鼠热缩足潜伏期（thermalwithdrawallatency，TwL），电子测痛仪检测小鼠机械痛缩足阈值（mechanicalwithdrawahhreshold，MWT），免疫组化法检测前扣带回c-Fos蛋白的表达，免疫印迹法检测总Car-1蛋白（t-Car-1）、磷酸化Car．1蛋白（p-Car-1）的表达变化。结果腹腔注射盐酸布桂嗪（0．1ms／10g）能够改善神经病理性疼痛小鼠痛行为，CCI＋BH组小鼠热缩足潜伏期在CCI后第5天[（5．92~0．61）S，P〈0．05]、第6天[（7．93±0．91）S，P〈0．01]、第7天[（9．12±0．69）S，P〈0．01]与第4天[（4．92±0．41）S]相比延长；与第4天[（1．55±0．31）g]相比，机械缩足阈值在第6天[（2．54±0．41）g，P〈0．01]、第7天[（3．68±0．61）g，P〈O．01]提高。免疫组化结果显示，盐酸布桂嗪可使神经病理性疼痛小鼠前扣带回c-Fos蛋白表达降低（P〈0．01）。免疫印迹显示，与CCI＋NS（t．Cav-1：2．87＋0．15，p-Car-1：0．48±0．09）组比较，盐酸布桂嗪可使神经病理性疼痛小鼠前扣带回t-Cav-1（1．97±0．31）、p-Cav-1（0．11±0．09）表达降低（均P〈O．01）。结论盐酸布桂嗪能够缓解神经病理性疼痛模型小鼠的热痛和机械痛行为，降低神经病理性疼痛小鼠前扣带回c-Fos、t-Cav-1、p-Car-1蛋白的表达。Objective To investigate the effects of Bucinnazine Hydrochloride on the pain behavior and the expression of caveolin-1 （Cav-1） in the anterior cingulate cortex of neuropathic pain mice. Methods 64 adult male Kunming mice （ 20-25g ） were divided randomly into 4 groups with 16 in each group： Sham＋BH（ Bucinnazine Hydrochloride） group, Sham＋NS （Normal Saline） group, CCI＋ BH group and CCI＋ NS group. The corresponding drugs were administered by intraperitoneal injectionfrom the forth day after CCI once a day for three days. Paw thermal withdrawal latency was measured by Hargreaves methods. Mechanicalwithdrawal threshold was assayed by electronic dolorimeter, c-Fos protein in anterior cingulate cortex was detected by immunohistochemistry staining and the expression of t-Cav-1, p-Cav-lwas detected by Western blot.Results Bucinnazine Hydrochloride administered by intraperitoneal injection （0.1 mg/10 g, mice）alleviated thermal hyperalgesia and mechanical allodynia of CCI mice. Compared with the torth day （4.92±0.41） s of CCI＋BH group, paw withdrawal latency on the fifth day （5.92±0.61）s was increased（P〈 0.05）, and on the sixth day（7.93±0.91 ）s and seventh day （9.12-＋0.69）s were increased more（P〈O.O1 ,P〈 0.0l ）.The paw withdrawal mechanical threshold on the sixth and seventh day of CCI＋BH group mice（ （2.54±0.41 ） g, （ 3.68±0.61 ） g） were increased significantly （P〈0.01 ,P〈0.01 ） compared with the forth day（ 1.55±0.31） g.hnmunohistochenistry results showed that the expression of c-Fos decreased after treated with Bucin- nazine Hydrochloride in the anterior cingulate cortex of CCI mice （P〈 0. 001） . Western Blotting showed that the expression of t-Cav- 1 （ 1,97±0.31 ） and p-Cav- 1 （0.11±0.09） in the anterior cingulate cortex of CCI ＋BH group mice decreased compared with that of in CCI ＋ NS group mice （ t-Cav- 1 ： 2.87± 0.15, p-Cav- 1 ： 0.48 ± 0.09） （P〈0.01 ,P〈0.01）. Conclusion Bueinnazine Hydr

关 键 词：盐酸布桂嗪 神经病理性疼痛 前扣带回 小窝蛋白1 C-FOS蛋白 

分 类 号：R-332[医药卫生] R741