三七总皂甙对吗啡戒断大鼠海马磷酸化CREB蛋白表达及CREB/DNA结合活性的影响

Effects of Panax Notoginseng on phosphorylated CREB protein expression and CREB/DNA binding activity in hippocampus of morphine withdrawal rats

目的:研究三七总皂甙(PNS)对吗啡依赖及纳络酮催促戒断大鼠海马组织CREB,pCREB蛋白表达及CREB/DNA结合活性的影响,探讨PNS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,采用腹腔注射纳络酮建立催促戒断模型,大鼠在给予吗啡的同时,采用4种不同剂量PNS进行灌胃.采用Westernblot和电泳迁移率改变分析法(EMSA)分别观察PNS对吗啡依赖及戒断大鼠海马组织总CREB,pCREB蛋白表达及CREB/DNA结合活性的影响.结果:①不同剂量PNS组、吗啡成瘾(MOR)组及纳络酮催促戒断(NAL)组大鼠海马组织总CREB蛋白表达与对照组相比无显著性差异(P>0.05);②MOR组pCREB蛋白表达及CREB/DNA结合活性数值略高于对照组(P>0.05),NAL组pCREB蛋白表达及CREB/DNA结合活性数值明显高于对照组和MOR组(P<0.01);③PNS可以剂量依赖性的抑制纳络酮催促戒断所引起的pCREB蛋白表达增高和CREB/DNA结合活性的增强.结论:PNS可以剂量依赖的抑制吗啡成瘾及纳络酮催促戒断诱导的大鼠海马组织CREB磷酸化和CREB/DNA结合活性的增强.

AIM： To investigate the effects of Panax Notoginseng （PNS） on the expressions of CREB, phosphorylated CREB （pCREB） and CREB/DNA binding activity in hippocampus of the morphine dependent rats and the naloxone-precipitated withdrawal syndrome rats, and to explore the mechanism by which PNS inhibits the morphine withdrawal symptom in rats. METHODS： The models of morphine physical dependent rats and withdrawal syndrome were established by subcutaneous injection of morphine in gradually increasing doses and abdominal cavity injection of naloxone respectively. The rats were treated with PNS by intragastric administration at various doses simultaneously when administrated with morphine. The effects of morphine on the expressions of CREB, pCREB, CREB/DNA binding activity in hippocampus were detected by Western blot and electrophoresis mobility shift assay （EMSA）. RESULTS ：① The CREB protein expression in hippocampus was not significantly statistically different in morphine physical dependent group （MOR）, naloxone precipitated withdrawal group （NAL） and PNS groups compared with control group （ P 〉 O. 05 ） ; ② The pCREB protein expression and CREB/DNA binding activity in hippocampus were not significantly increased in MOR compared with control group and were significantly increased in NAL compared with MOB and control groups; ③PNS could dose-dependently downregulate the increased expression of pCREB and CREB/DNA binding activity in hippocampus induced by naloxone-precipitated withdrawal. CONCLUSION： PNS could inhibit the expression of pCREB and CREB/DNA binding activity in hippocampus in a dose-dependent manner.