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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 relationship between adrenergic beta receptors and detrusor dysfunction in the elderly. Methods 10 elderly patients, 7 males and 3 females, aged 63 to 68 years. The control group of 7 patients, both men, aged 24 to 32 years. 2 groups of bladder function were normal, no male prostate disease. Bladder detrusor isolation after total hysterectomy. Cells were contracted with 40 mmol / L KCl solution to detect isoproterenol, BRL37344 (selective β3 receptor agonist), Forskolin (adenylate cyclase activator) and DBcAMP (dibutylcAMP) Relaxation effect on detrusor cells in two groups. Radioligand binding assay was used to detect the maximal binding sites (Bmax) and equilibrium dissociation constants (Kd) of β receptors in detrusor cells. Results KCl-induced detrusor myocytes shortened by 17.4% and 18.6% in the aged group and the control group, P> 0.05. The reactivity of bladder detrusor myocytes to isoproterenol, BRL347344 and Forskolin in the elderly group were significantly lower than those in the control group (all P <0.01), but the reactivity to DBcAMP was not significantly different from that in the control group (P > 0.05). The Bmax of detrusor beta receptor in the elderly group was significantly lower than that in the control group (26.9 and 32.4 fmol / mg protein, P <0.01), but there was no significant difference in Kd between the two groups (0.17 and 0.18 nmol / L, P > 0.05). Conclusion The decreased reactivity of adrenergic beta receptors in the bladder detrusor may be responsible for the decreased bladder compliance in the elderly. A decrease in cAMP synthesis resulting from decreased receptor density and decreased adenylyl cyclase activity may be the molecular basis for the decreased reactivity of adrenergic beta receptors.