国际麻醉学与复苏杂志
國際痳醉學與複囌雜誌
국제마취학여복소잡지
International Journal of Anesthesiology and Resuscitation
2015年
10期
876-879,887
,共5页
邹士雅%胡康%王刚%吴梦迪%王辉%曹君利%刘鹤
鄒士雅%鬍康%王剛%吳夢迪%王輝%曹君利%劉鶴
추사아%호강%왕강%오몽적%왕휘%조군리%류학
帕罗西汀%海马CA1区%神经病理性疼痛%脑源性神经营养因子
帕囉西汀%海馬CA1區%神經病理性疼痛%腦源性神經營養因子
파라서정%해마CA1구%신경병이성동통%뇌원성신경영양인자
Paroxetine%Hippocampal CA1 region%Neuropathic pain%Brain-derived neurotrophic factor
目的 观察新型抗抑郁药帕罗西汀对慢性压迫性损伤(chronic constriction injury,CCI)疼痛模型小鼠的镇痛作用,并探讨该作用与海马CA1区脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)表达变化的关系. 方法 雄性健康小鼠48只,采用随机数字表法分为假手术组(Sham组)和CCI模型组(CCI组),每组24只.两组小鼠于术后第3天开始分别给予帕罗西汀(20 mg· kg-1·d-1)或等量生理盐水(NS)灌胃,连续给药7d,从第8天开始停止给药,再分为Sham+P组、Sham+NS组、CCI+P组、CCI+NS组,每组12只.①于CCI模型建立后第0、3天,以及给药后第1、3、7、8、9、10、11天分别检测实验小鼠的热缩足潜伏期(paw withdrawal latency,PWL)变化.②将CCI+P组、CCI+NS组实验动物按随机数字表法随机分成CCI+P+BDNF组、CCI+P+磷酸盐缓冲液(phosphate buffered saline,PBS)组、CCI+NS+BDNF组、CCI+NS+PBS组,每组6只,帕罗西汀给药7d后于CCI对侧海马CA1区注射小剂量外源性BDNF(5 ng/0.2μl),观察BDNF注射后1、2、4 h小鼠的PWL变化. 结果 与Sham+NS组比较,Sham+P组小鼠灌胃后各时间点PWL无明显变化(P＞0.05);灌胃后第3、7天和停药第1天CCI+P组小鼠PWL分别为(6.66±0.35)、(8.36±0.33)s和(7.84±0.37)s,较CCI+NS组(5.01 ±0.24)、(5.58±0.40)、(6.24±0.35)s明显升高(P＜0.01、P＜0.001或P＜0.05);然而,停药第2天CCI+P组小鼠PWL与CCI+NS组比较,差异无统计学意义(P＞0.05);与CCI+NS+PBS组比较,CCI+NS+BDNF组在各时间点PWL差异均无统计学意义(P＞0.05);注药后1、2h和4h,CCI+P+BDNF组小鼠PWL分别为(5.78±0.39)、(5.34±0.47)s和(5.85±1.13)s,较CCI+P+PBS组(8.96±0.54)、(8.99±0.99)、(9.43±0.70)s明显降低(P＜0.01或P＜0.05). 结论 新型抗抑郁药帕罗西汀对神经病理性疼痛CCI模型小鼠有确切的镇痛效果,该作用与其调控海马BDNF表达有关.
目的 觀察新型抗抑鬱藥帕囉西汀對慢性壓迫性損傷(chronic constriction injury,CCI)疼痛模型小鼠的鎮痛作用,併探討該作用與海馬CA1區腦源性神經營養因子(brain-derived neurotrophic factor,BDNF)錶達變化的關繫. 方法 雄性健康小鼠48隻,採用隨機數字錶法分為假手術組(Sham組)和CCI模型組(CCI組),每組24隻.兩組小鼠于術後第3天開始分彆給予帕囉西汀(20 mg· kg-1·d-1)或等量生理鹽水(NS)灌胃,連續給藥7d,從第8天開始停止給藥,再分為Sham+P組、Sham+NS組、CCI+P組、CCI+NS組,每組12隻.①于CCI模型建立後第0、3天,以及給藥後第1、3、7、8、9、10、11天分彆檢測實驗小鼠的熱縮足潛伏期(paw withdrawal latency,PWL)變化.②將CCI+P組、CCI+NS組實驗動物按隨機數字錶法隨機分成CCI+P+BDNF組、CCI+P+燐痠鹽緩遲液(phosphate buffered saline,PBS)組、CCI+NS+BDNF組、CCI+NS+PBS組,每組6隻,帕囉西汀給藥7d後于CCI對側海馬CA1區註射小劑量外源性BDNF(5 ng/0.2μl),觀察BDNF註射後1、2、4 h小鼠的PWL變化. 結果 與Sham+NS組比較,Sham+P組小鼠灌胃後各時間點PWL無明顯變化(P＞0.05);灌胃後第3、7天和停藥第1天CCI+P組小鼠PWL分彆為(6.66±0.35)、(8.36±0.33)s和(7.84±0.37)s,較CCI+NS組(5.01 ±0.24)、(5.58±0.40)、(6.24±0.35)s明顯升高(P＜0.01、P＜0.001或P＜0.05);然而,停藥第2天CCI+P組小鼠PWL與CCI+NS組比較,差異無統計學意義(P＞0.05);與CCI+NS+PBS組比較,CCI+NS+BDNF組在各時間點PWL差異均無統計學意義(P＞0.05);註藥後1、2h和4h,CCI+P+BDNF組小鼠PWL分彆為(5.78±0.39)、(5.34±0.47)s和(5.85±1.13)s,較CCI+P+PBS組(8.96±0.54)、(8.99±0.99)、(9.43±0.70)s明顯降低(P＜0.01或P＜0.05). 結論 新型抗抑鬱藥帕囉西汀對神經病理性疼痛CCI模型小鼠有確切的鎮痛效果,該作用與其調控海馬BDNF錶達有關.
목적 관찰신형항억욱약파라서정대만성압박성손상(chronic constriction injury,CCI)동통모형소서적진통작용,병탐토해작용여해마CA1구뇌원성신경영양인자(brain-derived neurotrophic factor,BDNF)표체변화적관계. 방법 웅성건강소서48지,채용수궤수자표법분위가수술조(Sham조)화CCI모형조(CCI조),매조24지.량조소서우술후제3천개시분별급여파라서정(20 mg· kg-1·d-1)혹등량생리염수(NS)관위,련속급약7d,종제8천개시정지급약,재분위Sham+P조、Sham+NS조、CCI+P조、CCI+NS조,매조12지.①우CCI모형건립후제0、3천,이급급약후제1、3、7、8、9、10、11천분별검측실험소서적열축족잠복기(paw withdrawal latency,PWL)변화.②장CCI+P조、CCI+NS조실험동물안수궤수자표법수궤분성CCI+P+BDNF조、CCI+P+린산염완충액(phosphate buffered saline,PBS)조、CCI+NS+BDNF조、CCI+NS+PBS조,매조6지,파라서정급약7d후우CCI대측해마CA1구주사소제량외원성BDNF(5 ng/0.2μl),관찰BDNF주사후1、2、4 h소서적PWL변화. 결과 여Sham+NS조비교,Sham+P조소서관위후각시간점PWL무명현변화(P＞0.05);관위후제3、7천화정약제1천CCI+P조소서PWL분별위(6.66±0.35)、(8.36±0.33)s화(7.84±0.37)s,교CCI+NS조(5.01 ±0.24)、(5.58±0.40)、(6.24±0.35)s명현승고(P＜0.01、P＜0.001혹P＜0.05);연이,정약제2천CCI+P조소서PWL여CCI+NS조비교,차이무통계학의의(P＞0.05);여CCI+NS+PBS조비교,CCI+NS+BDNF조재각시간점PWL차이균무통계학의의(P＞0.05);주약후1、2h화4h,CCI+P+BDNF조소서PWL분별위(5.78±0.39)、(5.34±0.47)s화(5.85±1.13)s,교CCI+P+PBS조(8.96±0.54)、(8.99±0.99)、(9.43±0.70)s명현강저(P＜0.01혹P＜0.05). 결론 신형항억욱약파라서정대신경병이성동통CCI모형소서유학절적진통효과,해작용여기조공해마BDNF표체유관.
Objective To investigate the analgesic effect of the novel antidepressant drug paroxetine on the mice neuropathic pain induced by chronic constriction injury(CCI), and explore the relation between the analgesic effect of paroxetine and the change of brain-derived neurotrophic factor (BDNF) expression in hippocampal CA1 region.Methods Forty eight healthy male mice were randomly divided into two groups using the random number table method: Sham group and CCI group.From postoperative 3 d, the mices in two groups were orally given paroxetine or saline for 7 d.The drug administration was stopped on eighth day and then the mices were further divided into Sham+P group, Sham+NS group, CCI+P group and CCI+NS group (12 mices in each group.The paw withdrawal latency (PWL) was measured on 0 d and 3 d after the operation and 1, 3, 7, 8, 9, 10 d, and 11 d after drug administration, respectively.The animal in the CCI+P and CCI+NS groups were randomly divided into CCI+P+BDNF group, CCI+P+PBS group, CCI+NS+BDNF group and CCI+NS+PBS group (6 rats in each group).After 7 d of paroxetine treatment, small dose of exogenous BDNF was injected into contralateral hippocampus CA1 region in the CCI mices.Results Compared with Sham+NS group, the PWL at each time point after drug administration did not statistically differ in the Sham+P group (P＞0.05).Compared with CCI+NS group(5.01±0.24), (5.58±0.40), (6.24±0.35) s, the PWL was significantly increased at 3 d and 7 d after drug administration [(6.66±0.35) s and (8.36±0.33) s] and at 1 d after drug discontinuation [(7.84±0.37) s] in the CCI+P group (P＜0.01, P＜0.01 and P＜0.05).The PWL at 2 d after drug discontinuation was not statistically significant between the CCI+P and CCI+NS groups.Compared with the CCI+NS+PBS group, the PWL at each time point was not statistically difference in the CCI+NS+ BDNF group(P＞0.05).Compared with the CCI+P+PBS group (8.96±0.54), (8.99±0.99), (9.43±0.70) s, the PWL at 1, 2 h and 4 h after drug administration were significantly decreased in the CCI+P+BDNF group[(5.78±0.39), (5.34±0.47) s and (5.85±1.13) s, P＜0.001 or P＜0.05)].Conclusions The novel antidepressant paroxetine can produce significant analgesic effect on CCI-induced neuropathic pain and its analgesic effect are related to regulation of expression of BDNF in hippocampal CA1 region.
