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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.
Objective: To study the effect of Panax notoginseng saponins (PNS) on the expression of CREB, pCREB protein and CREB/DNA binding activity in hippocampus of morphine-dependent and naloxone-induced withdrawal rats, and to explore the mechanism of action of PNS in inhibiting morphine withdrawal symptoms. :Morphine hydrochloride was injected subcutaneously into the morphine somatotropy model by subcutaneous injection of morphine using a dose escalation method. The naloxone withdrawal model was established by intraperitoneal injection of naloxone. Rats were given intragastric administration with 4 different doses of PNS at the same time as morphine. Western blot and electrophoretic migration were used. The rate change assay (EMSA) was used to observe the effects of PNS on total CREB, pCREB protein expression and CREB/DNA binding activity in hippocampus of morphine-dependent and withdrawal rats. Results: 1 Different doses of PNS group and morphine addiction (MOR) group There was no significant difference in total CREB protein expression in hippocampus between naloxone-advance withdrawal (NAL) group and control group (P>0.05). The expression of CREB protein and CREB/DNA binding activity in MOR group was slightly higher than that in control group. In group (P>0.05), pCREB protein expression and CREB/DNA binding activity in NAL group were significantly higher than those in control group and MOR group (P<0.01); 3PNS dose-dependently inhibited naloxone-induced pCREB-induced withdrawal Increased protein expression CREB / DNA binding enhancing activity Conclusion:. PNS dose dependent inhibition of morphine and naloxone addiction withdrawal in rat hippocampal tissue induced phosphorylation of CREB and CREB / DNA binding enhancing activity.