安神药对对地西泮所致小鼠耐受性的抑制作用  

Long-term Application of Diazepam Lead to Body Tolerance in Mice and Inhibition of Sedative Chinese Medicine Pairs on Its Role

作　　者：丁莉[1] 潘怡宏[1] 游秋云[1] 王平[1] 

机构地区：[1]湖北中医药大学老年医学研究所,武汉430065

出　　处：《中国实验方剂学杂志》2014年第21期140-143,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金重点项目(81130064);国家自然科学基金面上项目(81072849)

摘　　要：目的:观察长期应用地西泮小鼠对药物的耐受性及不同安神药对对其的抑制作用,并初步探讨其机制。方法:将小鼠分为空白组、模型组、法半夏-秫米组(3.25 g·kg-1·d-1)、磁石-朱砂组(0.33 g·kg-1·d-1)、黄连-阿胶组(2.73 g·kg-1·d-1)、黄连-肉桂组(2.15 g·kg-1·d-1)、栀子-淡豆豉组(1.69 g·kg-1·d-1),每天灌胃(ig)1次,连续60 d。给药期间,除空白组外,各组隔2日于ig给药30 min后每3天1次ip地西泮注射液25 mg·kg-1,造成地西泮耐受。持续监测小鼠睡眠潜伏期,测定自主活动次数和时间,并用荧光定量PCR测定小鼠全脑γ-氨基丁酸受体(GABAA-R)mRNA、谷氨酸脱羧酶65(GAD65)mRNA的表达。结果:用药期间,模型组睡眠潜伏期逐渐延长,黄连-肉桂组、黄连-阿胶组睡眠潜伏期变化不大;用药2个月后,与模型组比较,黄连-肉桂组、黄连-阿胶组睡眠潜伏期明显缩短(P<0.01),黄连-肉桂组、黄连-阿胶组、法半夏-秫米组小鼠自主活动次数、活动时间显著性减少(P<0.05,P<0.01),黄连-肉桂组、黄连-阿胶组、半夏-秫米组、磁石-朱砂组和栀子-淡豆豉组小鼠脑组织GABAA-R mRNA,GAD65 mRNA表达显著性上调(P<0.05,P<0.01)。结论:黄连-阿胶、黄连-肉桂和法半夏-秫米具有抑制长期单独应用地西泮而致药效下降机体耐受的作用,其机制可能与上调脑内GABAA-R和GAD65有关。Objective：To observe the long-term application of diazepam on drug tolerance in mice and different sedative medicine for its inhibitory effect,and discussed its mechanism.Method：Mice were divided into blank control group,model control group,Pinelliae Rhizoma-Husked Sorghum group （3.25 g ·kg-1 ·d-1）,Magnetitum-Cinnabaris group （0.33 g ·kg 1·d 1）,Coptidis Rhizoma-Asini Corii Colla group （2.73 g ·kg-1· d 1）,Coptidis Rhizoma-Cinnamomi Cortex group （2.15 g·kg-1 ·d-1） and Gardeniae Fructus-Sojae Semen Praeparatum group （1.69 g ·kg-1·d-1）,orally once a day for 60 days.During the 60 days,except the blank control group,each group mice were injected with diazepam in 30 minutes after taking drugs （25 mg ·kg-1 ·3 d-1）.Continuously monitor the mice sleep latency,determination of autonomic activity frequency and time,using fluorescence quantitative PCR determination of whole brain gamma-aminobutyric acid receptors （GABAA-R） mRNA in mice,glutamic acid decarboxy lase 65 （GAD65） mRNA expression.Result：During the medication,sleep latency period of diazepam group extended gradually,Coptidis Rhizoma-Asini Corii Colla group and Coptidis Rhizoma-Cinnamomi Cortex group changed little; Medication after 2 months,compared with diazepam group,sleep latency period of Coptidis Rhizoma-Asini Corii Colla group and Coptidis Rhizoma-Cinnamomi Cortex group was obviously shortened （P ＜ 0.01）,and mice autonomic activity times and activity time of Coptidis RhizomaAsini Corii Colla group,Coptidis Rhizoma-Cinnamomi Cortex group and Pinelliae Rhizoma-Husked Sorghum group significantly reduced （P ＜ 0.05,P ＜ 0.01）,and Coptidis Rhizoma-Asinicorii Colla group,Coptidis RhizomaCinnamomi Cortex group,Pinelliae Rhizoma-Husked Sorghum group,magnetitum-cinnabaris group and gardeniaefructus-sojaesemenpraeparatum group mice brain GABAA-R mRNA and GAD65 mRNA expression significantly higher （P ＜0.05,P ＜0.01）.Conclusion：Coptidis Rhizoma-Asini Corii Colla,Coptidis RhizomaCinnamomi Cortex and Pin

关 键 词：地西泮 安神药对 耐受性 Γ-氨基丁酸 

分 类 号：R285.5[医药卫生—中药学]