三七皂苷对大鼠吗啡依赖戒断症状的抑制作用及对海马神经元内游离钙的影响

 目的 研究三七叶的三七皂苷(Arasaponins of Panax notoginseng leaves,APnL)对大鼠吗啡依赖及纳络酮催促戒断症状的抑制作用,以及对大鼠海马神经元内游离钙离子浓度(Ca2+]i)的影响,进一步探讨APnL抑制吗啡戒断症状的作用机制.方法 应用剂量递增法皮下注射盐酸吗啡建立吗啡躯体依赖模型,腹腔注射纳络酮建立催促戒断模型.在使用吗啡的同时,采用(50、100和200 mg/kg)3种剂量的APnL进行灌胃.第6天上午8:00末次注射吗啡50 mg/kg,观察各组催促戒断症状及体重减轻情况;1 h后急性分离海马神经元,并采用流式细胞技术检测了APnL对吗啡依赖大鼠海马神经元Ca2+]i的浓度.结果 ①剂量递增法慢性吗啡处理5 d后经ip NAL催促戒断后,与吗啡组相比可明显地诱发大鼠体重减轻和跳跃次数的发生(P＜0.01).②3种不同剂量APnL均可抑制大鼠戒断后体重减轻和跳跃的发生.③APnL可以有效地抑制纳络酮催促戒断所引起的大鼠海马神经元Ca2+]i浓度的降低,200 mg/kg剂量组作用最佳(P＜0.01).结论 APnL可以缓解纳络酮催促戒断诱导的吗啡成瘾大鼠戒断症状的发生,同时可以抑制纳络酮催促戒断所引起的大鼠海马神经元Ca2+]i浓度的降低.

Effects of arasaponins Panax notoginseng leaves on inhibiting withdrawal symptoms in morphine dependent rats and on intracellular calciumions in their hippocampal neurons

Objective To study the effects of ara saponins of Panax notoginseng leaves（APnL） on inhibiting naloxone - precipitated morphine withdrawal symptoms in morphine dependent rats, rat,s and on intracellular calciumions in hippecampus of morphine withdrawal rats. Methods The models of morphine physical dependent rats and withdrawal syndrome were developed by subcutaneous injection of morphine in gradually increasing doses and intraperitoneal injection of naloxone, respectively. The rats were treated with APnL given intragastrically in vari- ous doses at the same time when they developed naloxone - precipitated morphine withdrawal symptoms. On day 6,50 mg/kg morphine was in- jected at 8：00, Withdrawal syndrome was precipitated by intraperitoneal injection of naloxone （5 mg/kg）, The withdrawal syndrome and body weight loss were observed.After 1 hour,the hippocampal neurons were prepared from acutely isolated hippocampus The contents of Ca2＋ ]i of different groups were measured by flow cytometry. Results （1）Naloxone was intraperitoneally injected,5 days after chronic treatment with escalating doses of morphine. The body weight loss and number of jumping of morphine withdrawn rats were increased compared with morphine group （ P 〈 0.01）. （2）Three doses of ApnL decreased the body weight loss and number of jumping.
（3） APnL downregulated contents of Ca2＋ ]i in hippocampus in naloxone - precipitated withdrawal rats. 200 mg/kg was the best dose. Conclusion APnL significantly relieve the naloxone - precipitated withdrawal syndrome in morphine dependent rats and inhibit contents of Ca2＋ ]i in hippocampus of naloxone - precipitated withdrawal rats.