Department of Urology, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan; Center for Shockwave Medicine and Tissue Engineering, Chang Gung Memorial Hospital at Kaohsiung, Kaohsiung, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Department of Urology, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
Biomed J. 2022 Jun;45(3):482-490. doi: 10.1016/j.bj.2021.06.006. Epub 2021 Jul 2.
We examine the effects of low energy shock wave (LESW) on bladder and mitochondrial function in a rat model of HCl induced cystitis, and the influence of dynamic bladder filling volume on LESW responses. Dysregulation of mitochondria function may impact the urothelial barrier and contribute to bladder dysfunction in patients with Interstitial cystitis/bladder pain syndrome (IC/BPS).
Female Sprague-Dawley rats underwent urethral catheterization and intravesical instillation of 0.2 ml of 0.4 N HCl (N = 32) or 0.2 ml saline (N = 8) kept for 90 s. After HCl instillation, the bladder received LESW treatment while filled with 0 ml, 0.2 ml or 0.4 ml saline or no LESW treatment. Continuous cystometry (CMG) was performed on day 8. The bladder was harvested after CMG for histology and Western blotting.
HCl provoked bladder overactivity, bladder wall inflammation marked by infiltration of mast cells, increased bax/bcl2 ratio consistent with increased TUNEL staining and increased release of mitochondrial-integrity markers (cleaved caspase 3 and Cytochrome c). LESW treatment suppressed HCl provoked bladder overactivity in association with lower inflammatory reaction, mast cells infiltration, and a lower bax/bcl2 ratio also reflected by reduced TUNEL staining and mitochondrial-integrity markers irrespective of the volume of saline in bladder at the time of LESW.
These findings support that antiinflammatory effect of LESW in chemical cystitis is associated with the reversal of the molecular-cellular perturbations in mitochondrial dependent intrinsic apoptotic pathway.
本研究旨在通过盐酸诱导的膀胱炎大鼠模型，观察低能量冲击波（LESW）对膀胱和线粒体功能的影响，以及动态膀胱充盈量对 LESW 反应的影响。线粒体功能失调可能会影响尿路上皮屏障，并导致间质性膀胱炎/膀胱疼痛综合征（IC/BPS）患者的膀胱功能障碍。
雌性 Sprague-Dawley 大鼠接受尿道导管插入术，并向膀胱内灌注 0.2ml 的 0.4N HCl（N=32）或 0.2ml 生理盐水（N=8），保持 90s。盐酸灌注后，在膀胱充盈 0ml、0.2ml 或 0.4ml 生理盐水或不接受 LESW 治疗的情况下，对膀胱进行 LESW 治疗。在第 8 天进行连续膀胱测压（CMG）。CMG 后采集膀胱组织进行组织学和 Western blot 分析。
盐酸灌注引起膀胱过度活动，膀胱壁炎症表现为肥大细胞浸润，bax/bcl2 比值增加，与 TUNEL 染色增加和线粒体完整性标志物（裂解的 caspase 3 和细胞色素 c）释放增加一致。LESW 治疗抑制了盐酸引起的膀胱过度活动，同时伴有炎症反应减轻、肥大细胞浸润减少，bax/bcl2 比值降低，TUNEL 染色和线粒体完整性标志物减少，无论 LESW 时膀胱内生理盐水的体积如何。
这些发现支持 LESW 在化学性膀胱炎中的抗炎作用与逆转线粒体依赖性内在凋亡途径中分子-细胞扰动有关。
