肾上腺素能β受体与逼尿肌老化关系的研究  

Age-dependent alterations in β-adrenoceptor function in human detrusor and possible mechanism

作　　者：罗小冬 李刚[2] 王平[3] 

机构地区：[1]解放军第二○二医院泌尿外科,沈阳110003 [2]辽宁省肿瘤医院泌尿外科 [3]中国医科大学附属第四临床医院泌尿外科

出　　处：《中华泌尿外科杂志》2005年第7期455-457,共3页Chinese Journal of Urology

摘　　要：目的研究肾上腺素能β受体与老年人膀胱逼尿肌功能障碍的关系。方法老年组10例,男7例,女3例,年龄63～68岁。对照组7例,均为男性,年龄24～32岁。2组膀胱功能均正常,男性无前列腺病变。膀胱全切术后分离膀胱逼尿肌。采用细胞功能实验,以40mmol/LKCl溶液收缩细胞,检测异丙肾上腺素、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)对2组逼尿肌细胞的松弛效应。采用放射性配基结合实验检测2组逼尿肌细胞β受体的最大结合部位(Bmax)和平衡解离常数(Kd)。结果老年组和对照组KCl诱导逼尿肌细胞缩短17.4%和18.6%,P>0.05。老年组膀胱逼尿肌细胞对异丙肾上腺素、BRL347344和Forskolin的反应性均明显低于对照组(P值均<0.01),但对DBcAMP的反应性与对照组比较差异无统计学意义(P>0.05)。老年组逼尿肌细胞β受体的Bmax与对照组比较差异有统计学意义(26.9和32.4fmol/mg蛋白,P<0.01),但Kd差异无统计学意义(0.17和0.18nmol/L,P>0.05)。结论膀胱逼尿肌对肾上腺素能β受体的反应性下降可能是造成老年人膀胱顺应性减退的原因。β受体密度降低和腺苷酸环化酶活性下降导致的cAMP合成减少可能是造成肾上腺素能β受体反应性下降的分子基础。Objective To study the age-dependent alterations of bladder detrusor muscles in β-adrenergic responsiveness and possible mechanism. Methods Overall,10 elderly people (7 males and 3 females;age range,63-68 years) and 7 young men (controls;age range,24-32 years) were enrolled.Both groups had normal bladder function, and none of the males had prostate diseases.After total cystectomy, the bladder detrusor muscles were separated.The responsiveness to β-adrenergic agonists isoprenaline and BRL37344,forskolin and dibutyryl cyclic AMP (DBcAMP) of detrusor muscles from both groups were exa- mined by cellular functional test.Radioligand binding assay was also performed using non-selective β-adrenergic receptors ligand 3H-dihydroalprenolol ( 3H-DHA) to determine the Bmax and Kd of detrusor muscle cells in both groups. Results By KCl induction,the detrusor muscle cells in elderly group and control group were shortened by 17.4% and 18.6%,respectively (P>0.05).The responsiveness of detrusor muscle cells in elderly group to isoprenaline,BRL37344 and forskolin was significantly lower than that in control group ( P< 0.01);but there was no difference in the responsiveness to DBcAMP between the 2 groups ( P> 0.05 ).The Bmax of β-adrenoceptor was 26.9 fmol/mg and 32.4 fmol/mg in elderly and control groups,respectively,with significant difference between the 2 groups (P<0.01);but there was no significant difference in Kd (0.17 nmol/L vs 0.18 nmol/L) between the 2 groups (P>0.05). Conclusions There is an age-related decline in β-adrenergic responsiveness,which might be one of the causative factors of the reduced bladder compliance of the elderly.The decrease of cAMP level caused by reduced receptor density and adenylyl cyclase activity might be the molecular mechanisms underlying the changes of β-adrenergic responsiveness.

关 键 词：肾上腺素能Β受体 人膀胱逼尿肌功能障碍 Forskolin 逼尿肌细胞 Β3受体激动剂 放射性配基结合 对异丙肾上腺素 mol/L 反应性下降 老化 膀胱全切术后 环化酶激活剂 平衡解离常数 P>0.05 DBCAMP 对照组 前列腺病变 膀胱顺应性 

分 类 号：R694.54[医药卫生—泌尿科学]