糖尿病大鼠膀胱肾上腺素能α_1受体表达改变

Change of bladder α1-adrenoceptor expression at diabetic rat

目的研究糖尿病大鼠膀胱结构功能的改变及其肾上腺素能α1受体及其亚型的表达改变,并探讨其意义。方法采用1%链脲佐菌素(STZ)建立糖尿病大鼠的模型,实验分为正常对照组和糖尿病组。分别于2周、4周、6周进行在体充盈性膀胱测压评估膀胱功能,处死动物后取膀胱组织标本常规HE染色观察膀胱逼尿肌病理组织学变化,并采用Western blot与免疫荧光检测α1受体亚型(α1A受体与α1D受体)的表达改变。结果糖尿病大鼠体重减轻,尿量和膀胱湿重增加;充盈性膀胱测压检查结果显示糖尿病大鼠膀胱容量、顺应性、逼尿肌压力上升,残余尿量明显增加,排尿效率明显降低;常规HE染色光镜下观察可见糖尿病大鼠膀胱逼尿肌肌束进行性结构松散、紊乱,甚至出现肌束断裂。Western blott结果显示α1A受体及α1D受体的表达在逼尿肌中表达量随病程进行性下降,糖尿病组与正常对照组间对比差异有统计学意义。免疫荧光结果显示糖尿病膀胱实验组α1A受体和α1D受体灰度值均较相应对照组减少,且随病程进行性减少。结论糖尿病大鼠早期即可出现膀胱逼尿肌形态学和功能的改变,糖尿病膀胱中的α1-AR表达存在负相关关系,提示糖尿病可引起膀胱部位α1-AR表达减少。α1-AR表达减少可能是引起糖尿病膀胱顺应性增加,残余尿量增加的影响因素之一。

Objective To study changes of bladder＇s structure and functions, changes of distribution and expression of α1- adrenoceptor subtypes, and pathological changes of diabetes mellitus cystipathy in SD rats with diabetes mellitus （DM）. Methods Animal models of DM were made in SD rats by injecting 1% streptozotocin into abdomen. The rats were divided into normal control groups and DM groups in 2, 4 and 6 weeks by random allocation. Successively after 2, 4 and 6 weeks＇ time, rats underwent filling cystometry to estimate the bladder function, Western blot and immunofluorescence of bladder tissue sample were conducted to ob- serve pathological and histological changes in detrusor of bladder, and expression changes of Alpha receptor subtype （α1-AR and α1-AR）. Results Urine volume and bladder wet weight of DM rats increased with weight decreased compared with control groups. The results of filling cystometry in DM rats showed that bladder capacity, compliance, peak detrusor pressure and residual urine all increased distinctly, with decreased micturition efficiency. The routine HE staining under light microscopy showed there were progres- sively loose and disorder muscle bundles, even fracture ones in detrusor of DM rats. Western blot results showed α1A-AR and α1D-AR expressed decreasingly in detrnsor in DM rats. Immunofluorescence results showed the grey value of α1A-AR and α1D-AR positive cells in DM groups progressively reduced and were less than that of control groups. Conclusion Morphologieal and functional changes of detrusor of bladder occurred in early stage of DM rats. There was negative correlation between expression of α11-AR and DM disease, indicating DM may decrease expression of α1-AR in bladder, of which the decreased expression may be one of factors to cause in- creased bladder compliance and residual urine in DM disease.