盐酸小檗碱改善慢性炎症痛和抑郁的作用研究  

The effect of berberine on ameliorating chronic inflammatory pain and depression

作　　者：徐芳 杨婧 孟波[2] 郑晋伟[2] 廖奇[1] 陈骏萍[2] 陈晓薇[1] Xu Fang, Yang Jing, Meng Bo, Zheng Jinwei, Liao Qi, Chen Junping, Chen Xiaowei(Zhejiang Provincial Key Laboratory of Pathophysiology , Medical School of Ningbo University, Ningbo 315211, Chin)

机构地区：[1]宁波大学医学院浙江省病理生理学重点实验室,315211 [2]宁波市第二医院麻醉科

出　　处：《中华医学杂志》2018年第14期1103-1108,共6页National Medical Journal of China

基　　金：国家自然科学基金（81671089）;浙江省自然科学基金（LY15H090011）;宁波市自然科学基金（2016A610086,2016A610144）;宁波市生命健康科技创新团队一重大精神疾病转化医学（2015C110026）;浙江省医药卫生科技计划（No.2017KY591）;浙江省公益技术应用研究计划项目（No.2017C37126）;宁波市第二医院华美研究基金（2017HMKY34）

摘　　要：目的探讨盐酸小檗碱（BBR）对小鼠慢性炎症痛及其伴发的抑郁样症状的影响及其机制。方法本实验使用雄性ICR小鼠40只，2月龄，体质量25～30g。采用小鼠足底注射完全弗氏佐剂（CFA）的方法建立慢性痛动物模型。应用随机数字表法将小鼠分为4组（n=10）：生理盐水组（A组）、慢性痛组（B组）、生理盐水＋BBR组（C组）、慢性痛＋BBR组（D组）。所有动物在注射CFA或生理盐水之前均进行疼痛和抑郁行为学实验以测量行为学基线值。之后在实验第1天（d1），B组和D组足底注射50出CFA（生理盐水1：1稀释），A组和C组足底注射等量生理盐水；在d15-d21，C组和D组腹腔注射BBR50mg／kg，共持续7d，A组和B组注射等容量生理盐水。通过Hargreaves方法和Von Frey纤毛在建模以前、d7、d14、d17和d21分别进行热痛和机械痛阈值测定；通过强迫游泳和摄食抑制实验在建模以前和d21进行抑郁样行为指标测定。在行为学结束之后处死所有动物，取L4～L5段脊髓采用酶联免疫吸附试验（ELISA）检测各组小鼠脊髓中白细胞介素18（IL-1β）、白细胞介素6（IL-6）和肿瘤坏死因子α（TNF-α）的水平，并通过实时定量聚合酶链反应（qRT—PCR）分析CC趋化因子配体2（CCL2）的mRNA水平。结果与A组相比，B组小鼠在d7、d14、d17、d21的热痛阈值均显著降低[（3．40±0．67）S比（10．55±1．58）s、（7．49±1．04）S比（11．47±1．92）S、（6．46±0．56）S比（11．60±1．86）S、（6．04±0．54）S比（10．33±1．59）S，均P〈0．01]，机械痛阈值均显著降低[（0．15±0．03）g比（0．78±0．24）g、（0．23±0．12）g比（0．60±0．16）g、（0．30±0．12）g比（0．72±0．25）g、（0．40±0．00）g比（0．72±0．19）g，均P〈0．01]，在d21强迫游泳不动时间延长[（161．60±35．79）s比（88．92±53．24）S，P〈0．05]，摄食潜伏期延长[（227．Objective To explore the effect of berberine on chronic inflanlmatory pain and the comorbid depression and the associated mechanisms. Methods Forty healthy male ICR mice （2 months, 25- 30 g） were used in the present study. The chronic inflammatory pain was induced by intraplantar injection of complete freund＇s adjuvant （CFA） to the hind paws. All animals were divided into 4 groups （n = 10 for each group） according to random number table： the saline group （group A） , the chronic pain group （ group B） , the saline ± berberine group （ group C ） and the chronic pain ± berberine group （ group D） o The baseline data of pain and depressive performance were measured on the day before any drug treatment. On dl, mice of B and D groups received iutraplantar injections of 50μl CFA emulsion （ 1 ： 1 diluted with saline） ; mice of A and C groups received intraplantar injections of the same volume of saline. During d15 -d21, mice of C and D groups received intraperitoneal injections of berberine （50 mg/kg, daily for 7 days） ; mice of A and B groups received the equal volume of saline. The Hargreaves tests and the Von Frey tests were conducted before the injection of CFA and on d7, d14, d17 and d21 to measure the thermal and mechanical pain thresholds. The forced swimming tests and novelty-suppressed feeding tests were performed before the injection of CFA and on d21 to measure the depressive performance. After the behavioral tests, the levels of inflammatory cytokines interleukin-1β （IL-1β）, interleukin-6 （IL-6）, tumor necrosis factor-α（TNF-α） at the lumbar （IA -L5 ） spinal cord were examined by enzyme-linked immunosorbent assay（ELISA）. The mRNA level of chemokine C-C motif ligand 2 （CCL2） in the lumbar spinal cord was examined by quantitative real-time polymerase chain reaction （qRT-PCR）. Results Compared with group A, the thermal withdrawal latency of group B mice on d7,d14,d17,d21 was declined [ （3.40 ±0.67）s vs （10.55 ± 1.58）s,（7.49 ±1.

关 键 词：炎症 疼痛 抑郁 治疗结果 

分 类 号：R285.5[医药卫生—中药学]