摘要
目的验证独立于环磷酸腺苷-蛋白激酶A(cAMP-PKA)信号通路之外的环磷酸腺苷-鸟嘌呤核苷酸交换因子(cAMP-Epac)通路是否参与介导芬太尼致呼吸抑制,同时对该通路是否参与芬太尼的镇痛、镇静效应进行评价。方法通过小鼠肺功能参数检测、热板、翻正反射实验,考察Epac激动剂8-pCPT对芬太尼致小鼠呼吸抑制的肺功能参数变化、镇痛效应、翻正反射消失率及翻正反射诱导时间和制动时间的影响,明确Epac信号通路是否参与了芬太尼致呼吸抑制、镇痛、镇静等生物学效应。结果肺功能参数检测表明,8-pCPT可改善芬太尼导致的呼吸频率、分钟通气量降低,抑制芬太尼导致的吸气时间和呼气时间升高,提示Epac可能参与了芬太尼引起的呼吸抑制效应。热板实验结果表明,给予8-pCPT后各对应组小鼠在15 min时最大可能镇痛百分率无明显差异,提示Epac可能与芬太尼镇痛效应无关。翻正反射实验结果表明,给予Epac激动剂后各对应组小鼠芬太尼翻正反射诱导时间、制动时间、翻正反射消失率均无明显变化,提示Epac可能与芬太尼镇静效应也无关。结论Epac激动剂8-pCPT可改善芬太尼所致呼吸抑制效应,不影响芬太尼的镇痛、镇静效应,提示Epac通路可能单独介导了芬太尼导致的呼吸抑制效应。
Objective To find out whether the cyclic adenosine monophosphate-exchange protein directly activated by cAMP(cAMP-Epac)pathway,which is independent of the cyclic adenosine monophosphate-protein kinase A(cAMPPKA)signaling pathway,is involved in mediating fentanyl-induced respiratory depression,and to evaluate whether the pathway is involved in the analgesic and sedative effects of fentanyl.Methods The effects of Epac agonist 8-pCPT on fentanyl-induced respiratory depression,analgesia,sedation respiratory depression,and righting reflex disappearance were evaluated in mice based on respiratory function parameters,55℃hot plate test and LORR(Loss of righting reflex)test.Results The detection of pulmonary function parameters showed that 8-pCPT could reverse the decrease in the respiratory rate and minute ventilation caused by fentanyl,and inhibit the increase in inspiratory time and expiratory time caused by fentanyl,suggesting that Epac might have been involved in fentanyl-induced respiratory depression.There was no significant difference in the possible maximum percentage of analgesia at 15 min between groups of mice after 8-pCPT administration in the 55℃hot plate test,which suggested that Epac might not be related to the analgesic effect of fentanyl.The results of the LORR test showed that there was no significant change in the percentage of LORR,time to loss of righting reflex or time to recovery of righting reflex in any group of mice after 8-pCPT administration.Epac might not be involved in the sedative effect induced by fentanyl.Conclusion The Epac agonist 8-pCPT can improve the respiratory depression induced by fentanyl,but does not affect the analgesic and sedative effects induced by fentanyl,which indicates that the Epac pathway may only be related to respiratory depression caused by fentanyl.
作者
王泽宇
苏瑞斌
雍政
罗文哲
WANG Ze-yu;SU Rui-bin;YONG Zheng;LUO Wen-zhe(Jiamusi University,Jiamusi,Heilongjiang 154004,China;Department of New Drug Evaluation,State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)
出处
《军事医学》
CAS
2021年第11期852-856,共5页
Military Medical Sciences
