神经源性膀胱A型肉毒毒素膀胱壁注射后逼尿肌超微结构观察

Ultrastructure of detrusor of neurogenic bladder following botulinum toxin type A injection in bladder wall

目的观察脊髓损伤(SCI)导致逼尿肌过度活动的神经源性膀胱患者膀胱壁A型肉毒毒素(BTX-A)注射后逼尿肌超微结构的变化。方法以15例逼尿肌过度活动的SCI患者作为研究对象。其中2例未接受BTX-A注射;7例首次接受膀胱壁BTX-A注射;5例接受第2次膀胱壁BTX-A注射;1例接受第3次膀胱壁BTX-A注射。在注射BTX-A后即刻用膀胱镜活检钳留取逼尿肌组织,48 h内制作成标本,透射电镜观察超微结构变化。结果透射电镜下,未接受膀胱壁BTX-A注射逼尿肌的肌细胞形状多样、排列紊乱;肌细胞核增大、不规则;线粒体肿胀、内质网扩张;肌细胞间中间连接减少、胞膜形成广泛的锯齿状胞突连接、质膜下胞饮小泡或胞膜凹陷减少;细胞间隙增宽,间质中可见排列紊乱的胶原纤维和少许弹性纤维。首次接受膀胱壁BTX-A注射者与未注射者的逼尿肌超微结构特征基本相同。接受第2次注射和第3次注射者的逼尿肌超微结构与首次注射和未注射者比较无明显差异,只是改变程度稍有加重。结论逼尿肌过度活动的SCI患者膀胱壁BTX-A单次或重复注射后,未观察到膀胱逼尿肌超微结构出现特异性的不可逆改变。提示膀胱壁BTX-A注射治疗神经源性膀胱是一种安全、可逆、可重复的微创治疗方法。

Objective To observe the changes in ultrastructure of detrusor following botulinum toxin type A （BTX-A） injection in bladder wall in neurogenic bladder patients with detrusor overactivity caused by spinal cord injury （SCI）. Methods Fifteen SCI patients with detrusor overactivity were enrolled. Two patients did not receive BTX-A injection, 7 received first BTX-A injection in bladder wall, 5 received second BTX-A injection in bladder wall, and 1 received third BTX-A injection in bladder wall. The detrusor tissues were obtained immediately after BTX-A injection with cystoscopic biopsy forceps and specimens were processed within 48 h. Transmission electron microscopy was employed to observe the changes in ultrastructure. Results For the patients without BTX-A injection, detrusor muscle cells were multiform and disorderly arranged, and nucleolus were augmented and irregular. The mitochondrial swelling, dilatation of endoplasmic reticula, reduction of intermediate between muscle cell junctions, and more gaps and protrusion junctions between membranes were observed. Besides, the intercellular spaces were dilated obviously, with abundant collagen fibers and less elastic fibers. For those with first BTX-A injection, the characteristics of detrusor uhrastructure resembled those without BTX-A injection. For those with second or third BTX-A injection, only small degree of increase in changes of detrusor ultrastructure was found when compared with those with first BTX-A injection or without BTX-A injection, and no significant difference was observed. Conclusion No specific and irreversible changes in ultrastructure of detrusor of bladder were observed after single or repeated BTX-A injection in bladder wall in SCI patients with detrusor overactivity. BTX-A injection in bladder wall is a safe, reversible, repeatable and minimally-invasive procedure in the treatment of neurogenic bladder.