Smith Katrina J, Chess-Williams Russ, McDermott Catherine
Faculty of Health Sciences & Medicine, Bond University, Gold Coast, QLD 4229, Australia.
Biomed Res Int. 2014;2014:347616. doi: 10.1155/2014/347616. Epub 2014 May 18.
DMSO is used as a treatment for interstitial cystitis and this study examined the effects of luminal DMSO treatment on bladder function and histology. Porcine bladder was incubated without (controls) or with DMSO (50%) applied to the luminal surface and the release of ATP, acetylcholine, and LDH assessed during incubation and in tissues strips after DMSO incubation. Luminally applied DMSO caused ATP, Ach, and LDH release from the urothelial surface during treatment, with loss of urothelial layers also evident histologically. In strips of urothelium/lamina propria from DMSO pretreated bladders the release of both ATP and Ach was depressed, while contractile responses to carbachol were enhanced. Detrusor muscle contractile responses to carbachol were not affected by DMSO pretreatment, but neurogenic responses to electrical field stimulation were enhanced. The presence of an intact urothelium/lamina propria inhibited detrusor contraction to carbachol by 53% and this inhibition was significantly reduced in DMSO pretreated tissues. Detection of LDH in the treatment medium suggests that DMSO permeabilised urothelial membranes causing leakage of cytosolic contents including ATP and Ach rather than enhancing release of these mediators. The increase in contractile response and high levels of ATP are consistent with initial flare up in IC/PBS symptoms after DMSO treatment.
二甲基亚砜(DMSO)被用作间质性膀胱炎的一种治疗方法,本研究检测了腔内应用DMSO对膀胱功能和组织学的影响。将猪膀胱在无(对照组)或向腔内表面应用DMSO(50%)的情况下进行孵育,并在孵育期间以及DMSO孵育后的组织条中评估三磷酸腺苷(ATP)、乙酰胆碱和乳酸脱氢酶(LDH)的释放情况。腔内应用DMSO在处理过程中导致ATP、乙酰胆碱和LDH从尿路上皮表面释放,组织学上也明显可见尿路上皮层的缺失。在来自经DMSO预处理膀胱的尿路上皮/固有层条中,ATP和乙酰胆碱的释放均受到抑制,而对卡巴胆碱的收缩反应增强。逼尿肌对卡巴胆碱的收缩反应不受DMSO预处理的影响,但对电场刺激的神经源性反应增强。完整的尿路上皮/固有层的存在使逼尿肌对卡巴胆碱的收缩受到53%的抑制,而在经DMSO预处理的组织中这种抑制作用显著降低。在处理培养基中检测到LDH表明,DMSO使尿路上皮细胞膜通透性增加,导致包括ATP和乙酰胆碱在内的胞质内容物泄漏,而不是增强这些介质的释放。收缩反应的增加和高水平的ATP与DMSO治疗后间质性膀胱炎/膀胱疼痛综合征(IC/PBS)症状的最初突然发作一致。