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1、吗啡联合丁丙诺啡治疗大鼠骨癌痛的基础研究周亮董彦鹏孙亮武林鑫张朝宾王稳北京协和医学院中国医学科学院肿瘤医院麻醉科北京100021通信作者:孙莉,医学,北京协和医学院中国医学科学院肿瘤医院麻醉科,麻醉与镇痛专业,主任医师【】目的探讨不同剂量丁丙诺啡联合叼啡治疗大鼠骨癌痛的效果及机制.方法选择成年雌性Wistar大鼠64只,,随机分为8组(n=8),即空白对照组(C组)、吗啡10mg/kg组(M组)、吗啡10mg/kg+丁丙诺啡20ug/kg组(MB1组)、吗啡10mg/kg+丁丙诺啡40ug/kg
2、组(MB2组)、吗啡10mg/kg+T丙诺啡60ug/kg组(MB3组)、丁丙诺啡50ug/kg+丁丙诺啡20ug/kg组(BB1组)、丁丙诺啡50ug/kg+丁丙诺啡40ug/kg组(BB2组)、丁丙诺啡50ug/kg+丁丙诺啡60ug/kg组(BB3组),分别于每日7:00am和7:00pm进行皮下注射,连续8H,每H7:00pm给药后30min进行疼痛行为学测定即甩尾实验,Westen-blot测定中枢神经系统阿片受体的表达情况.结果给药第7、8日,甩尾实验,MB1,MB2组较M组,抗伤害
3、痛阈升高;MB1MB2组较M组,PAG和LC以及腰段脊髓MOR的上调以及LC和腰段脊髓KOR的下调.结论低剂量丁丙诺啡延缓骨癌痛大鼠吗啡耐受,可能通过抑制PAG和LC以及腰段脊髓MOR的下调以及LC和腰段脊髓KOR的上调来实现.【关键词】丁丙诺啡;呵啡耐受;骨癌痛;阿片受体[Abstract]ObjectiveToexplorethetherapeuticeffectsandmechanismofdifferentdosesofbuprenorphinecombinedwithmorphinef
4、orbonecancerpaininrats.MethodsSixty—fouradultfemaleWistarrats,weighing160—200g,wererandomlydividedinto8groups(n=8each):morphine10mg/kggroup(groupM),morGphine10mg/kg+buprenorphine20ug/kggroup(groupMB1),morphine10mg/kg+buprenorphine40ug/kggroup(groupMB
5、2),morphine10mg/kg+buprenorGphine60ug/kggroup(groupMB3),buprenorphine50ug/kg+buprenorphine20ug/kggroup(groupBB1),buprenorphine50ug/kg+buprenorphine40ug/kggroup(groupBB2),buprenorphine50ug/kg+buprenorphine60ug/kggroup(groupBB3)andcontrolgroup(groupC).
6、Morphineand/orbuprenorphineweresubcutaneouslygiventwiceaday(at7:00amand7:00pm,respectively)for8consecutivedays.andallratsunderwentafterAntinociceptionwasdeterminedbytailflicklantency(TFL)tohotwaterat(52±0.5)°C.TFLwasmeasuredat7:30pmforthe8cons
7、ecutivedays.Westen—blotanalysiswasusedtoexaminetheexpressionofopioidreceptors??proteinincentralnervesystem.ResultsTail—flicklatencyofgroupMB1andgroupMB2islongerthanthatofgroupMandgroupC(P<0.001).MORproGteinandDORproteininPGweredown—regulatedwhileMOR?
8、?S,KOR??sandDOR??SproteininLCandlumbosacralspinalcordwereup—regulatedingroupM.TheproteinofMORwasup—regulatedinPAGofbothgroupMB1andgroupMB2.TheproteinofKORwasdown—regulatedinPAGandlumbosarcralspinalcordofgroupMB1comparedwiththoseingroupM(P<0.001).Conc