Járomi Péter, Szabó Andrea, Garab Dénes, Bodnár Dóra, Uhercsák Gabriella, Boros Mihály, Hartmann Petra
Bács-Kiskun Megyei Önkormányzat Kórháza Urológiai Osztály Kecskemét.
Magy Seb. 2012 Aug;65(4):184-90. doi: 10.1556/MaSeb.65.2012.4.3.
The vascular endothelium is a primary target of ischemia/reperfusion (IR) injury of the urinary bladder. In case of interstitial cystitis (painful bladder syndrome) or in cyclophosphamide-induced hemorrhagic cystitis, the injury is initiated at the epithelial/urothelial surface and propagates towards the interstitium, causing secondary involvement of the microvasculature. Hence the aim of our study was to assess and compare the microcirculatory aspects of the non-infectious forms of cystitis with that of IR-caused reactions.
In male Sprague-Dawley rats, interstitial cystitis was induced by intravesical instillation of protamine sulphate (2 mg in 200 μl saline for 30 min; n = 6). In another group, cyclophosphamide (75 mg/kg, ip) was administered 24 hr prior to the experiments (n = 5). In the third group, urinary bladder ischemia was induced by 60-min occlusion of the vessels supplying the bladder (n = 5). The microcirculatory inflammatory reactions were investigated by fluorescence intravital microscopy 60 min after reperfusion and 24 hr after protamine sulphate instillation or cyclophosphamide administration, respectively. In the control group, the bladder was instilled with saline (n = 5).
Rolling of leukocytes increased ~3-fold in the postcapillary vessels in the protamine sulphate-treated group and the increase in this parameter was ~5 and ~6.5-fold in cyclophosphamide and IR groups, respectively. The increase in leukocyte adherence reached similar, approx. 7-fold increase in each of the challenged groups. The red blood cell velocity in the capillaries decreased in the protamine sulphate and IR groups, while the velocity increased moderately in the cyclophosphamide-treated group.
Our results demonstrate that direct endothelial injury (caused by IR), as well as protamine sulphate and cyclophosphamide administrations induce inflammatory microcirculatory changes of the urinary bladder. These observations suggest a causative role for microcirculatory disturbances in the pathogenesis of interstitial cystitis and hemorrhagic cystitis as well.
血管内皮是膀胱缺血/再灌注（IR）损伤的主要靶点。在间质性膀胱炎（疼痛性膀胱综合征）或环磷酰胺诱导的出血性膀胱炎中，损伤始于上皮/尿路上皮表面，并向间质扩散，导致微血管继发性受累。因此，我们研究的目的是评估和比较非感染性膀胱炎形式与IR引起的反应的微循环方面。
在雄性Sprague-Dawley大鼠中，通过膀胱内灌注硫酸鱼精蛋白（2mg溶于200μl生理盐水中，持续30分钟；n = 6）诱导间质性膀胱炎。在另一组中，在实验前24小时给予环磷酰胺（75mg/kg，腹腔注射）（n = 5）。在第三组中，通过阻断供应膀胱的血管60分钟诱导膀胱缺血（n = 5）。分别在再灌注后60分钟以及硫酸鱼精蛋白灌注或环磷酰胺给药后24小时，通过荧光活体显微镜检查研究微循环炎症反应。在对照组中，膀胱灌注生理盐水（n = 5）。
在硫酸鱼精蛋白治疗组中，毛细血管后血管中白细胞滚动增加约3倍，在环磷酰胺组和IR组中该参数的增加分别约为5倍和6.5倍。白细胞黏附的增加在每个受挑战组中达到相似的约7倍增加。硫酸鱼精蛋白组和IR组中毛细血管内红细胞速度降低，而环磷酰胺治疗组中速度适度增加。
我们的结果表明，直接的内皮损伤（由IR引起）以及硫酸鱼精蛋白和环磷酰胺给药均可诱导膀胱的炎症性微循环变化。这些观察结果表明微循环紊乱在间质性膀胱炎和出血性膀胱炎的发病机制中也起因果作用。
