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低强度体外冲击波疗法改善链脲佐菌素诱导的糖尿病大鼠的糖尿病低活动膀胱。

Low-intensity extracorporeal shockwave therapy ameliorates diabetic underactive bladder in streptozotocin-induced diabetic rats.

机构信息

Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA.

Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

出版信息

BJU Int. 2018 Sep;122(3):490-500. doi: 10.1111/bju.14216. Epub 2018 Apr 20.

Abstract

OBJECTIVES

To evaluate the therapeutic effect of once-weekly low-intensity extracorporeal shock wave therapy (Li-ESWT) on underactive bladder (UAB) in the streptozotocin (STZ)-induced diabetic rat model.

MATERIALS AND METHODS

In all, 36 female Sprague-Dawley rats were divided into three groups: normal control (NC), diabetes mellitus control (DMC), and DM with Li-ESWT (DM Li-ESWT). The two DM groups received an intraperitoneal 60 mg/kg STZ injection to induce DM. The Li-ESWT was applied toward the pelvis of the rats starting 4 weeks after STZ administration and lasting for 4 weeks. The Li-ESWT was given once weekly, with an energy flux density of 0.02 mJ/mm at 3 Hz for 400 pulses. All rats underwent conscious cystometry, leak-point pressure (LPP) assessment, ex vivo organ-bath study, histology, immunofluorescence, and Western Blot analysis.

RESULTS

Conscious cystometry revealed voiding dysfunction in the DMC group, whereas the DM Li-ESWT group showed significantly improved voiding function, reflected in a reduced post-void residual urine volume and increased LPP compared to the DMC group. Ex vivo organ-bath studies showed that Li-ESWT enhanced muscle contractile activity of the bladder and urethra during electrical-field stimulation and drug stimulation. Histologically, Li-ESWT significantly restored bladder morphology, reflected by a reduction in the intravesical lumen area and increased muscle proportion of the bladder wall. Western Blot analysis showed higher smooth muscle actin expression in the bladder wall in the DM Li-ESWT group compared to the DMC group. Immunofluorescence showed decreased nerve-ending distribution, and destroyed and shortened nerve fibres in the DMC group, and recovery of neuronal integrity and innervation in the DM Li-ESWT group.

CONCLUSIONS

In conclusion, Li-ESWT ameliorated UAB and urinary incontinence in the diabetic UAB rat model. The improvement appears to be the result of restoration of bladder and urethral structure and function by Li-ESWT. Li-ESWT is non-invasive and may become a better alternative therapy for UAB. Further investigations are warranted.

摘要

目的

评估每周一次低强度体外冲击波治疗(Li-ESWT)对链脲佐菌素(STZ)诱导的糖尿病大鼠模型下尿路功能障碍(UAB)的治疗效果。

材料和方法

共 36 只雌性 Sprague-Dawley 大鼠分为三组:正常对照组(NC)、糖尿病对照组(DMC)和 Li-ESWT 糖尿病组(DM Li-ESWT)。两组糖尿病大鼠腹腔注射 60mg/kg STZ 诱导糖尿病。Li-ESWT 在 STZ 给药后 4 周开始应用于大鼠骨盆,持续 4 周。Li-ESWT 每周进行一次,能量通量密度为 0.02mJ/mm,3Hz 时进行 400 个脉冲。所有大鼠均进行清醒膀胱测压、漏点压(LPP)评估、离体器官浴研究、组织学、免疫荧光和 Western Blot 分析。

结果

清醒膀胱测压显示 DMC 组存在排尿功能障碍,而 DM Li-ESWT 组表现出明显改善的排尿功能,表现为残余尿量减少,LPP 增加,与 DMC 组相比差异有统计学意义。离体器官浴研究显示,Li-ESWT 增强了膀胱和尿道在电场刺激和药物刺激下的肌肉收缩活性。组织学上,Li-ESWT 显著恢复了膀胱形态,表现为膀胱内腔面积减小,膀胱壁肌肉比例增加。Western Blot 分析显示,DM Li-ESWT 组膀胱壁平滑肌肌动蛋白表达高于 DMC 组。免疫荧光显示,DMC 组神经末梢分布减少,神经纤维受损和缩短,DM Li-ESWT 组神经完整性和神经支配恢复。

结论

总之,Li-ESWT 改善了糖尿病 UAB 大鼠模型的 UAB 和尿失禁。改善似乎是 Li-ESWT 恢复膀胱和尿道结构和功能的结果。Li-ESWT 是一种非侵入性治疗方法,可能成为 UAB 的更好替代治疗方法。需要进一步研究。

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