Chen Yen-Ta, Yang Chih-Chao, Sung Pei-Hsun, Lin Kun-Chen, Chiang John Y, Huang Chi-Ruei, Huang Kuan-Hui, Chuang Fei-Chi, Chu Yi-Ching, Huang Eng-Yen, Yip Hon-Kan
Division of Urology, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University Kaohsiung, Taiwan.
Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital Kaohsiung, Taiwan.
Am J Transl Res. 2020 Mar 15;12(3):999-1015. eCollection 2020.
This study tested the long-term effect of extracorporeal shock wave (ECSW) therapy on ameliorating radiotherapy-induced chronic cystitis (CC) in rat.
Adult-female SD rats (n = 24) were equally categorized into group 1 (normal control), group 2 (CC induced by radiotherapy with 450 cGy twice with a four-hour interval to the urinary bladder), group 3 [CC with ECSW treatment (0.1 mJ/mm/120 impulses once every 3 days after radiotherapy)]. Bladder specimens were harvested by day 60 after radiotherapy. By day 60, the degree of detrusor contraction was significantly reduced in group 2 than groups 1 and 3, and significantly reduced in group 3 than in group 1 (P < 0.0001). Number of WBC, occulted blood and bacteria were significantly higher in group 2 than in groups 1 and 3 (P < 0.01), but they showed no difference between the latter two groups (P > 0.3). The protein expressions of oxidative stress (NOX-1/NOX-2/oxidized protein), apoptosis (cleaved-caspase-3/cleaved-PARP), DNA-damaged marker (γ-H2AX), fibrosis (TGF-β/Smad3) and inflammatory signaling (TLR-4/MYD88/Mal/TRAF6/p-IκBα/p-NFκB/TNF-α/MMP-9/COX-2) were significantly higher in group 2 than in group 1, and were significantly reduced in group 3 (all P < 0.001). The cellular expressions of inflammatory (CD14+/CD68+/MIF+/MMP-9), immunoreactive (CD4+/CD8+) and cytokeratin (CK17/CK18) biomarkers, and collagen-deposition/fibrotic areas as well as bladder-damaged score/disruption of the bladder mucosa displayed an identical pattern compared to that of oxidative stress among the three groups (all P < 0.0001).
The long-term effect of ECSW treatment was reliable on protecting the urinary bladder from radiation-induced CC.
本研究测试了体外冲击波(ECSW)疗法对改善大鼠放射性慢性膀胱炎(CC)的长期效果。
成年雌性SD大鼠(n = 24)被平均分为1组(正常对照组)、2组(膀胱接受450 cGy放射治疗,分两次,间隔4小时)、3组[CC伴ECSW治疗组(放疗后每3天一次,0.1 mJ/mm/120次脉冲)]。放疗后第60天采集膀胱标本。至第60天,2组逼尿肌收缩程度显著低于1组和3组,3组显著低于1组(P < 0.0001)。2组白细胞、潜血和细菌数量显著高于1组和3组(P < 0.01),但后两组间无差异(P > 0.3)。氧化应激(NOX-1/NOX-2/氧化蛋白)、凋亡(裂解的半胱天冬酶-3/裂解的PARP)、DNA损伤标志物(γ-H2AX)、纤维化(TGF-β/Smad3)和炎症信号(TLR-4/MYD88/Mal/TRAF6/p-IκBα/p-NFκB/TNF-α/MMP-9/COX-2)的蛋白表达在2组显著高于1组,在3组显著降低(均P < 0.001)。炎症(CD14+/CD68+/MIF+/MMP-9)、免疫反应(CD4+/CD8+)和细胞角蛋白(CK17/CK18)生物标志物的细胞表达,以及胶原沉积/纤维化区域和膀胱损伤评分/膀胱黏膜破坏在三组中的表现与氧化应激模式相同(均P < 0.0001)。
ECSW治疗对保护膀胱免受辐射诱导的CC的长期效果可靠。