肾上腺素能β受体在人膀胱逼尿肌中作用的年龄相关性研究  

Age-dependent changes of beta-adrenoceptor function in human detrusor urinae and possible mechanisms

作　　者：李振华[1] 马智勇[1] 李刚[1] 王平[1] 孔垂泽[1] 

机构地区：[1]中国医科大学附属第一医院泌尿外科,沈阳市110001

出　　处：《中华老年多器官疾病杂志》2004年第3期178-181,共4页Chinese Journal of Multiple Organ Diseases in the Elderly

基　　金：国家自然科学基金资助 (编号 3 0 170 3 5 2 )

摘　　要：目的　研究肾上腺素能 β受体膀胱逼尿肌反应性的年龄相关性改变及其可能机制。方法　采用细胞功能试验来检测 10位老年患者逼尿肌细胞对异丙肾上腺素 (肾上腺素能β受体激动剂 )、BRL37344 (选择性 β3受体激动剂 )、forskolin(腺苷酸环化酶激活剂 )和DBcAMP(二丁基环腺苷酸 )的反应性。同样用非选择性肾上腺素能 β受体配基 [3H]-双氢心得舒来进行放射性配基结合测定。并以青年人的膀胱逼尿肌标本作为对照。结果　对照组和老年组之间KCl诱导的逼尿肌收缩程度无显著性差异 ;与对照组相比 ,老年组对异丙肾上腺素、BRL37344和forskolin的反应性分别下降了 15 .0 %、17.6 %和 12 .6 % (P <0 .0 0 1) ,异丙肾上腺素和BRL37344的pD2 ( lgEC50 )值也显著降低 ;两组间对DBcAMP的反应性并无差别 ;随年龄增加逼尿肌细胞的肾上腺素能 β受体的最大结合部位显著下降 ,但平衡解离常数却无明显差别。结论　老年人膀胱平滑肌存在对肾上腺素能 β受体的反应性下降 ,这可能是造成老年人膀胱顺应性减退的原因。受体密度的降低和腺苷酸环化酶活性的下降导致的cAMP合成减少可能是造成肾上腺素能Objective To study age-depend en t changes of beta-adrenoceptor responsiveness and their possible mechanisms. Methods Responsiveness of detrusor urinae from 10 old patients to the beta-adrenergic agonists isoprenaline, BRL37344, forskolin, and dibutyryl c yclic AMP (DBcAMP) was examined by using a cellular function test. A radioligand binding assay was performed using the non-selective beta-adrenergic receptor ligand [ 3H]-dihydroalprenolol ([ 3H]-DHA). Specimens from 10 yo ung men were used as controls. Results There were no age-depende nt changes in contractile response to KCl. The relaxation responses to isoprenal ine, BRL37344, and forskolin decreased by 15.0%, 17.6%, and 12.6%, respectively (P<0.001) in the aged group. The pD2 values for isoprenaline and BRL37344 al so declined significantly. There was no difference in the responsiveness to DBcA MP between the two groups. The maximum binding site decreased significantly with increasing age, but the equilibrium-dissociation constant did not change. Conclusions There is an age-related decline in beta-adrenergic re sp onsiveness which might be one of the causative factors of reduced bladder comp li ance in the elderly. A decrease in cAMP level caused by reduced receptor density and adenylyl cyclase activity might be the underlying molecular mechanism of th e changes in beta-adrenoceptor responsiveness.

关 键 词：肾上腺素能Β受体 膀胱 逼尿肌 年龄 相关性 分子机制 

分 类 号：R69[医药卫生—泌尿科学]