雌性素缺乏會惡化高糖高脂飲食所誘發的過動性膀胱-大白鼠動物模式
阮雍順1,2,3,4、 李懿倫4,5、吳文正1,2,3、 張美玉3、 何婉婷1、 劉克明8、 莊淑棉9
高雄醫學大學 泌尿科1，醫學研究所2， 解剖科8， 轉譯醫學中心9；
高雄市立小港醫院 泌尿科3；高雄醫學大學附設中和紀念醫院 泌尿科4；
衛生署立旗山醫院 外科部 泌尿科5；
Ovary hormone deficiency exacerbated high fat and high sugar diet - induced overactive bladder in a rat model
Yung-Shun Juan1,2,3,4, Yi-Lun Lee4,5, Wen-Jeng Wu1,2,3, Mei-Yu Jang3, Wan-Ting Ho1, Keh-Min Liu8*, Shu-Mien Chuang9*
1Department of Urology, 4Graduate Institute of Medical Science, 8Department of Anatomy, College of Medicine, 9Translational Research Center, Cancer Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 2Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;3Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan;5Department of Urology, Chi-Shan Hospital, Department of Health, Executive Yuan, Kaohsiung, Taiwan;
Purpose: The pathophysiology mechanism of menopause in the metabolic syndrome associated bladder dysfunction is still not clear. The major aims of the present study were to examine high-fat-high-sugar diet and surgical menopause - induced metabolic syndrome by elucidating the critical role of oxidative stress mediated by mitochondria and endoplasmic reticulum in overactive bladder.
Materials and Methods: Female Sprague-Dawley rats were feed with high-fat-high-sugar diet with/without ovariectomy surgery to mimic menopause and to induce metabolic syndrome. At six months after high-fat-high-sugar feeding, cystometrogram, physical indicator, urine and serum biochemistry parameters were measured. The terminal deoxynucleotidyl transferase nick-end labeling assay was performed to evaluate the distribution of apoptotic cells. Immunofluorescence studies and Western blots were carried out to examine the expressions of muscarinic and purinergic receptors, fibrosis-associated proteins, mitochondria stress markers, apoptosis-associated proteins and mitochondrial respiratory subunits enzymes.
Results: Bladder hyperactivity was induced accompanied by bladder interstitial fibrosis after 6 months of high-fat-high-sugar feeding, while surgical menopause exacerbated these bladder damages. In addition, surgical menopause enhanced the generation of oxidative stress mediated by mitochondria-dependent pathways, and consequently attributed to bladder apoptosis. Such oxidative stress-enhanced bladder cell apoptosis and urothelial barrier defects were potential factors that might play crucial role in bladder over-activity and interstitial fibrosis. Ovary hormone deficiency with high-fat-high-sugar feeding also induced bladder dysfunction via over-expression of muscarinic and purinergic receptors.
Conclusions: High-fat-high-sugar feeding enhanced the generation of oxidative stress mediated by mitochondria, while ovary hormone deficiency enhanced bladder apoptosis and interstitial fibrosis, exacerbated overactive bladder syndrome.