李懿倫^1,2、陳建升¹、吳炳男^2,3、莊淑棉⁴、吳文正^2,5,7、阮雍順^2,6,7

¹衛生福利部新營醫院泌尿科；²高雄醫學大學醫學院 醫學研究所，³藥學部，⁴醫學研究部癌症中心轉譯研究中心；⁵高雄市立大同醫院泌尿科；⁶高雄市立小港醫院泌尿科；         ⁷高雄醫學大學附設醫院泌尿科

Wheather GREEN TEA CATECHINS COULD HAVE A PROTECTIVE EFFECT IN OVERACTIVE BLADDER RATS INDUCED BY HIGH-SUGAR HIGH-FAT DIET AND OVARIECTOMY？

Yi-Lun LEE^1,2, Wen-Chi Chen¹, Bin-Nan Wu^2,3, Shu-Mien Chuang⁴, Wen-Jeng Wu^2,5,7 , Yung-Shun Juan^2,6,7

Department of Urology, Sinying Hospital, Ministry of Health and Welfare, Tainan, Taiwan¹；The Graduate Institute of Medical Science² and Department of Pharmaology³ ,College of Medicine, and Translational Research Center⁴, Cancer Center, Department of Medical Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Urology, Kaohsiung Municipal Ta-Tung Hospital⁵；Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital⁶；Department of Urology, Kaohsiung Medical University Hospital⁷, Kaohsiung, Taiwan

 

Purpose: To evaluate whether green tea catechins, epigallocatechin gallate (EGCG) could prevent bladder from the stress and injury of hypercholesterolmic and hyperglycemic diet in a ovariectomized rat model. Moreover, to elucidate that high-sugar and high-fat diet with ovariectomy could result in any influences and cell damages of bladder tissues.

Materials and Methods: Sixty female Sprague-Dawley rats were divided randomly into five groups. The first groups served as the normal diet control, the second groups were fed with high-sugar high-fat diet(HFHS),the third groups were received ovariectomy and fed with high-sugar high-fat diet(OVX+HFHS),the fourth groups were fed with high-sugar high-fat diet and injected with EGCG 10 μM/kg/day intraperitoneally(HFHS+EGCG), and the fifth groups were received ovariectomy, fed with high-sugar high-fat diet and injected with EGCG 10 μM/kg/day intraperitoneally(OVX+HFHS+EGCG). All rats were sacrificed after 6mons diet feeding and drug administration. Cystometrograms were performed for the measure of bladder over-activities. Masson’s trichrome stain was used to observe the histological change of bladder tissues. Western immunoblots and RT-PCR were performed to determine the expressions of inflammatory markers, fibrotic markers, antioxidants and caspases cascade reaction proteins.

Results: After 6 months, high-sugar high-fat feeding could induce the overactive bladder symptoms, such as frequent urination, reduced voiding volume and decreased compliance in rats. In ovariectomized rats with high-sugar high-fat diet, their overactive bladder symptoms will be more severely accompanied by the presentation of involuntary voiding contractions. High-sugar high-fat diet would induce significantly overexpression of TGF-β, fibronectin and type I collagen. In terms of catechin EGCG treatment will significantly reduce TGF-β, fibronectin, and typeI collagen performance. High-sugar high-fat diet also enhanced overexpression of MnSOD mRNA, while EGCG treatment alleviated the increase of MnSOD. In addition, high-sugar high-fat diet might elicit caspase cascade reaction in bladder ttissues of rats, leading to release of cytochrome c from mitochondria, increasing the caspase 9 activation, and making the overexpression of caspase 3 and PARP. However, EGCG treatment can reduce the expressions of caspases induced by high-sugar high-fat diet and alleviate the phenomenon of apoptotic reaction in bladder tissue.

Conclusions: High-fat high-sugar diet and ovariectomy both could induce frequent urination and reduce compliance of bladder and then elicit the overexpressions of fibrotic markers and caspase cascade reaction proteins. EGCG could restore high-sugar high-fat and ovariectomy induced bladder dysfunction through anti-inflammatory, and anti-apoptotic pathways.