探討戊聚醣多硫酸鈉作為預防泌尿道感染的角色
丁慧恭1、顏敬恆2、褚兆軒3、范綱毅4、程君弘4、蒙恩1,3
1三軍總醫院 外科部 泌尿外科； 2三軍總醫院松山分院 外科部 泌尿外科；3國防醫學院 生物化學研究所；4國防醫學院 生物及解剖學科
The efficacy of pentosan polysulfate sodium therapy for preventing urinary tract infections in rats
Hui-Kung Ting,1 Jing-Heng Yan,2 Chu Chao Hsuan,3 Gang-Yi Fan,1 Juin-Hong Cherng,4 En Meng1,3
1Division of Urology, Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan; 2Division of Urology, Tri-Service General Hospital, Songshan Branch, Taipei, Taiwan; 3Department and Graduate Institute of Biochemistry, National Defense Medical Center, Taipei, Taiwan; 4Department and Graduate Institute of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan
Purpose:
Urinary tract infection (UTI) frequently recur and result in long-term effects damage in the lower urinary tract. Our purpose of the study is to investigate the efficacy of pentosan polysulfate sodium (PPS) in UTIs prevention. We develop a rat model of UTIs and analyze whether PPS can ameliorate the UTI symptoms and infectious status.
Materials and Methods:
Total eighty-six female Sprague-Dawley rats were involved in establishing UTI model. 2x107 uropathogenic E.colli (UPEC) suspension was instilled via catheter into the bladder of the anesthesia rat. For PPS efficacy study, all animals are randomized into 4 groups: healthy control group; the PPS-pretreated group (prevention UTI, gavage with PPS 20 mg/kg/day for 14 days); the PPS-treated group (treatment UTI, gavage with PPS 20 mg/kg/day for 28 days); and the UTI model group (gavage normal saline). The urine, blood samples, and bladder and kidney tissues of UTI rats were collected after sacrifices on day 1, 3, 7, and 14 after UPEC catheterizing. We also analyzed the histology of bladder and inflammatory response in rats.
Results:
The bacteria are particularly abundant in the urine of UTI group, the count was greater than 107~108 CFU/ml of escherichia coli in urine, the UTI rat model has been established successfully. Our histological data show the transitional epithelium and the underlying muscle layer of UTI bladder become impaired due to UPEC damage, indicated that the ability of bladder protection in corrosive damage to urine was deficient. In addition, the PPS prevention group shown the level of bacteriuria in urine and WBC analysis are decrease, indicating that PPS has the potential of preventing UTI occur. According to UPECs have a greater potential to induce IL-1β, we found the higher concentrations of IL-1β in UTI rats were preserved than healthy rats after UPEC infection for 14 days, on the contrary, both of PPS-pretreated and treated group shown decrease of IL-1β production. The results indicated that PPS may attenuate toxicity of UPEC virulence factors. Further studies are required to understand the relationship between underlying mechanisms and the interactions of UPEC pathways.
Conclusion:
The recurrence rate of UTIs is very high, our results highlight the PPS effect in the pathogenesis of UTIs, especially in PPS-pretreated group presented reduce inflammation after UPEC infection. We suggest that the clinical application of PPS still needs to combine with adequate water consumption and good urination habits may prevent UTIs.