低能量體外震波用於治療由代謝症候群及荷爾蒙缺乏引發之膀胱過動: 大鼠模式研究

邱泰樺¹、呂建和²、阮泰叡³、闕光瞬^4,5,6、莊淑棉⁶、沈美珍⁶、孫婷瑋⁶、阮雍順^1,4,6

¹高雄醫學大學附設中和紀念醫院 泌尿部; ²國立屏東科技大學 工學院 環境工程與科學系 新興污染物研究中心; ³國防醫學院, 醫學系; ⁴高雄醫學大學 醫學院 臨床醫學研究所; ⁵高雄市立大同醫院 泌尿科; ⁶高雄醫學大學 醫學院 泌尿學科

Low-Intensity Shock Wave Therapy in Treating Bladder Overactivity Induced by Metabolic Syndrome and Hormonal Deficiency: A Rat Model Study

Tai-Hua Chiu¹, Jian-He Lu², Tai-Jui Juan³, Kuang-Shun Chueh^4,5,6, Shu-Mien Chuang⁶, Mei-Chen Shen⁶, Ting-Wei Sun⁶, Yung-Shun Juan^1,4,6

¹Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;

²Emerging Compounds Research Center, Department of Environmental Science and Engineering, College of Engineering, National Pingtung University of Science and Technology, Taiwan;

³Department of Medicine, National Defense Medical College, Taipei, Taiwan;

⁴Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;

⁵Department of Urology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan;

⁶Department of Urology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 

Purpose: Metabolic Syndrome (MetS) and ovarian hormone deficiency (OHD) are linked to bladder overactivity and lower urinary tract symptoms. Individuals with MetS are at a two to three-fold higher risk of developing overactive bladder (OAB), which impairs bladder storage function. Low-intensity extracorporeal shock wave therapy (LiESWT) is clinically utilized to reduce inflammation, enhance angiogenesis, stimulate cell proliferation, and expedite wound healing. This study aimed to explore the efficacy of LiESWT in increasing angiogenesis and regulating signaling molecules to control detrusor muscle hyperactivity in a rat model with metabolic syndrome and ovarian hormone deficiency.

Materials and Methods: Female Sprague-Dawley rats were categorized into five groups: (1) Control group with a normal rat chow diet, (2) MetS group induced by a high-fat, high-sugar (HFHS) diet, (3) MetS + LiESWT group, induced with the HFHS diet and treated with LiESWT (4 weeks, twice a week, 0.12 mJ/mm^2, 300 impulses at 3Hz), (4) MetS + OVX group, induced by the HFHS diet plus bilateral ovary removal (OVX), (5) MetS + OVX + LiESWT group, induced by the HFHS diet and bilateral OVX, followed by LiESWT treatment. Cystometrogram studies and tracing analyses of voiding behavior were conducted, alongside Masson’s trichrome staining, to investigate pathological changes in the bladder post-treatment. The expressions of various markers were thoroughly analyzed. These included inflammatory and fibrosis markers, urothelial differentiation markers, adhesion proteins, proliferation markers, tight junction proteins, proteins related to interstitial cells, angiogenesis-related proteins, and cell signaling proteins. The analysis employed Western blotting and real-time quantitative PCR (RT-qPCR) techniques.

Results: The findings indicated that both the MetS and MetS + OVX groups exhibited significant bladder capacity reduction and increased bladder overactivity. Conversely, LiESWT treatment mitigated bladder hyperactivity, improved pathological changes, and influenced bladder angiogenic remodeling and interstitial cell generation. LiESWT treatment augmented the expression of endoplasmic reticulum (ER) stress proteins and modulated ER-related Ca2+ channels/receptors to regulate detrusor muscle contractility. Additionally, LiESWT enhanced angiogenesis protein expression and increased the protein phosphorylation of ErK1/2, P38, and Akt.