盐酸关附甲素对大鼠血管舒缩功能的影响及其机制  

Effects and machanisms of Guanfu base-A on vasomotion of rats

作　　者：陆家凤[1] 可燕[1] 蒋嘉烨[1] 栗源[1] 李晓军[1] 

机构地区：[1]上海中医药大学教学实验中心,上海201203

出　　处：《中国药理学通报》2012年第7期952-956,共5页Chinese Pharmacological Bulletin

基　　金：国家科技部"十一五"支撑计划(No 2006BA11B08-03);上海高校青年教师培养资助计划(No shzy017)

摘　　要：目的研究盐酸关附甲素(guanfu base-A,GFA)对大鼠离体胸主动脉舒缩功能的影响,并探讨其可能机制。方法将SD大鼠胸主动脉分离并制成血管环,分成内皮完整组和去内皮组,采用离体血管环实验,观察GFA对基础状态,氯化钾(KCl)预收缩及苯肾上腺素(phenylephrine,PE)预收缩的血管舒张功能的影响,并结合不同抑制剂及无钙液处理,探讨其舒张血管的可能机制。结果累积浓度的GFA(10-8～10-4mol·L-1)对基础状态或KCl预收缩的有无内皮的血管环的张力均无明显影响(P>0.05);对PE(10-6mol·L-1)预收缩内皮完整的血管有浓度依赖性舒张作用,而与PE预收缩的去内皮组相比,从10-7mol·L-1开始差异有显著性(P<0.01)。一氧化氮合酶抑制剂L-NAME、鸟苷酸环化酶抑制剂亚甲蓝及环氧合酶抑制剂吲哚美辛孵育后,均能明显抑制GFA的扩血管作用(P<0.01);经无钙液及GFA处理后,胸主动脉对PE的反应性降低(P<0.01)。结论 GFA对大鼠胸主动脉的舒张作用主要通过两种途径:内皮依赖性舒张作用的机制主要与NO-GC-cGMP途径及激活环氧合酶有关;非内皮依赖性舒张机制主要与抑制内钙释放有关,与门控钙通道引起的外钙内流无关。Aim To investigate the vasorelaxation and vasoconstriction effects of GFA on the isolated thoracica aorta and to discuss its possible mechanism.Methods The thoracica aorta removed from the rats were divided into endothelium intacted and endothelium-detached groups in the organ bath system.The effect of GFA on the tension of the aortic rings in the basic state,precontracted with KCl,PE or several inhibitors and Ca2＋ free medium were observed.Results Accu-mulated GFA（10-7~10-4 mol·L-1） had no vasorelaxation effect on aortic rings in basis tension or precontracted with KCl,but it had endothelium-dependent vasorelaxation after being pre-constricted with PE.Vasorelaxation effect was greatly decreased after being pre-incubated by L-NAME,methylene blue or indomethacin.After dealing with Ca2＋ free medium and GFA,the vasoconstriction reaction to PE decreased.Conclusions GFA has vasorelaxation effect on rat endothelium intacted thoracica aorta in a concentration-dependent manner.The endothelium-dependent mechanism may be connected with NO-GC-cGMP pathway and activation of cyclooxygenase.The endothelium-independent relaxation may be induced by inhibiting of intracellular Ca2＋ release,but independent with extra cellular Ca2＋ inflow.

关 键 词：关附甲素 离体血管环 内皮 血管舒张 钙通道 一氧化氮 

分 类 号：R-332[医药卫生] R322.12