摘要
目的研究以转录因子CREB为靶点的CRE-decoy ODN对大鼠吗啡戒断症状的影响。方法合成全硫代磷酸化ODN。实验分为5组:0.9%氯化钠溶液对照组,侧脑室0.9%氯化钠溶液注射对照组,吗啡依赖组,吗啡戒断组,吗啡戒断CRE-decoy ODN治疗组。制备吗啡身体依赖模型:采用递增剂量皮下注射吗啡建立大鼠吗啡身体依赖模型。0.9%氯化钠溶液对照组和侧脑室0.9%氯化钠溶液注射对照组大鼠注射等体积0.9%氯化钠溶液。对吗啡戒断治疗组大鼠在末次吗啡注射前30h,每只大鼠于左侧侧脑室内注射CRE-decoy ODN 20μg,侧脑室0.9%氯化钠溶液注射对照组、吗啡依赖组和吗啡戒断组每只大鼠则于左侧侧脑室内注射等体积0.9%氯化钠溶液。吗啡戒断大鼠的行为学评定:腹腔注射纳络酮后,由不知情的观测者随即观测大鼠的戒断行为,每15分钟为一时间段,连续观测1h内上述行为的发生频率,最后计算戒断0～60min的总评分。进行体重丢失的戒断评分:体重丢失百分率(ΔW)=纳络酮注射前与注射1h后的体重差/纳络酮注射前体重×100%。结果 CRE-decoy ODN明显抑制吗啡戒断大鼠0～60min戒断症状的总评分,使其从(24.0±0.7)分降至(15.0±0.9)分(P<0.01)。CRE-decoy ODN明显抑制吗啡戒断大鼠0～60min的体重丢失,反映戒断症状综合性指标的体重丢失百分率ΔW从(7.2±1.2)%降至(4.1±0.8)%(P<0.01)。结论 CRE-decoy ODN明显减轻吗啡戒断大鼠的戒断症状。
Objective To investigate the effects of CRE-decoy ODN targeting transcription factor CREB on morphine withdrawal symptoms in rats. Methods Firstly,24-mer phospborothioate ODNs was synthesized. The rats were randomly divided into 5 groups：normal saline （NS） control group, i. c. v. saline-injection control group, morphine physicaldependent group, naloxone-precipitated withdrawal group, CRE-decoy ODN-treated withdrawal group. Then the morphine physical -dependent models were established by subcutaneous injection with morphine hydrochloride 10mg/kg,with increasing the drug dose progressively. The rats in normal saline control group were injected with 0.9% NS and the rats in i. c. v. NS control group were injected with 0.9% NS into lateral ventricles of the rats. The rats in CRE-decoy ODN-treated withdrawal group were injected with CRE-decoy ODN 20μg into lateral ventricles of each rat 30 hours before last morphine injection, and the rats in the other 3 groups were injected with equal - volume 0.9% NS into left lateral ventricles of the rats. The behavior evaluation of morphine withdrawal rats was as follows：after intraperitoneal injection with naloxone, the withdrawal behaviors of the rats were observed by the unwitting researches, with an interval of 15 minutes, and the incidence of the behaviors mentioned above was observed continuously for 1 hour, at last, the total scores between 0 - 60 min were calculated. The withdrawal scores of body weight loss were determined according to the formula： body weight loss percentage （△W） = the difference before naloxone injection and 1 hour after naloxone injection/body weight before naloxone injection × 100%. Results The CRE-decoy ODN decreased obviously the total scores of morphine withdrawal rats between 0 - 60min, from 24.0 ±0.7 to 15.0 ±0.9 （ P 〈0.01 ）. The CRE-decoy ODN inhibited obviously the body weight loss of morphine withdrawal rats between 0 ± 60rain,which showed that body weight loss percentage was decreased from （7.2±1.2）% to（4.1 ±0.8）% （ P 〈0.01）. Conclusion The CRE-decoy ODN can significantly suppress morphine withdrawal symptoms in rats.
出处
《河北医药》
CAS
2011年第18期2732-2734,共3页
Hebei Medical Journal
