Wang Hung-Jen, Lee Wei-Chia, Tyagi Pradeep, Huang Chao-Cheng, Chuang Yao-Chi
Department of Urology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
The Center of Excellence in Shockwave Medicine and Tissue Regeneration, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Neurourol Urodyn. 2017 Aug;36(6):1440-1447. doi: 10.1002/nau.23141. Epub 2016 Dec 30.
Low energy shock wave (LESW) is known to facilitate tissue regeneration with analgesic and anti-inflammatory effects. We examined the effects of LESW on the expression of inflammatory molecules, pain behavior, and bladder function in a rat cystitis model.
Control and experimental animals were injected with saline or cyclophosphamide (CYP; 75 mg/kg intraperitoneally) on day 1 and 4. After lower midline incision, the bladders were exposed to LESW (300 pulses, 0.12 mJ/mm ) or sham operation on day 2. In study 1 (N = 12, 4 for each group), the nociceptive effects of CYP were evaluated for 30 min by behavioral assessment on day 4 one hour after CYP injection. In study 2 (N = 21, 7 for each group), continuous cystometry (CMG) was performed on day 8. The bladder was harvested after behavioral assessment or CMG for histology and Western blotting.
CYP-induced upregulation of COX2 and IL6 expression, caused pain behavior (eye closing and hypolocomotion), and bladder inflammation was noted on days 4 and 8 along with bladder hyperactivity. LESW treatment reduced pain behavior and downregulated the NGF expression (33.3%, P < 0.05) on day 4 and IL6 (40.9%, P < 0.05). LESW treatment suppressed bladder overactivity (intercontraction interval 77.8% increase, P < 0.05) by decreasing inflammation and COX2 (38.6%, P < 0.05) expression and NGF expression (25.2%, P = 0.0812).
CYP-induced bladder pain, inflammation, and overactivity involves activation of IL6, NGF, and COX2 expression. These changes are suppressed by LESW, indicating it as a potential candidate for relieving bladder inflammatory conditions and overactivity.
已知低能量冲击波(LESW)具有促进组织再生、镇痛和抗炎作用。我们在大鼠膀胱炎模型中研究了LESW对炎症分子表达、疼痛行为和膀胱功能的影响。
在第1天和第4天,对照组和实验组动物分别注射生理盐水或环磷酰胺(CYP;75mg/kg腹腔注射)。在腹正中线下部切口后,于第2天将膀胱暴露于LESW(300脉冲,0.12mJ/mm²)或进行假手术。在研究1(N = 12,每组4只)中,于CYP注射后1小时,在第4天通过行为评估对CYP的伤害性作用进行30分钟的评估。在研究2(N = 21,每组7只)中,于第8天进行连续膀胱测压(CMG)。在行为评估或CMG后收集膀胱用于组织学检查和蛋白质免疫印迹分析。
CYP诱导COX2和IL6表达上调,导致疼痛行为(闭眼和活动减少),并且在第4天和第8天观察到膀胱炎症以及膀胱活动亢进。LESW治疗在第4天减轻了疼痛行为,并下调了NGF表达(降低33.3%,P < 0.05)和IL6表达(降低40.9%,P < 0.05)。LESW治疗通过减轻炎症以及COX2表达(降低38.6%,P < 0.05)和NGF表达(降低25.2%,P = 0.0812)抑制了膀胱活动亢进(收缩间期增加77.8%,P < 0.05)。
CYP诱导的膀胱疼痛、炎症和活动亢进涉及IL6、NGF和COX2表达的激活。这些变化被LESW抑制,表明LESW是缓解膀胱炎症状态和活动亢进的潜在候选方法。