Expression of Nitric Oxide Synthase and Aquaporin-3 in Cyclophosphamide Treated rat Bladder
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Purpose: The expression of Nitric oxide Synthase (NOS) and aquaporin (AQP) water channels in rat bladder is recently reported. The aim of this study is to evaluate the expression of inducible NOS (iNOS), aquaporin-3 (AQP-3) in cyclophosphamide (CYP) induced rat bladder. Materials and Methods: The 32 Sprague-Dawley rats were divided into cystitis group (n=20) and control group (n=12). In cystitis group, 100mg/kg CYP was injected every second day for 1 week whereas in control group, normal saline was injected. After extracting of the bladder and dividing dome, body and trigone of the bladder, independently H&E staining and immunohistochemical staining for iNOS and AQP-3 were performed. Expressions of iNOS and AQP-3 were analyzed with a confocal laser scanning microscope and an image analyzer. Results: The expression of iNOS significantly increased in the mucosa, submucosa layer of dome in cystitis group (p<0.05).The expression of AQP-3 significantly increased in the mucosa, submucosa, vessel layer of dome in cystitis group (p<0.05). Conclusions: These results suggest that inflammatory change activates NOS and AQP-3 expression in the bladder tissue of rats. These may imply that NOS and AQP-3 have a pathophyiological role in the cyclophophamide induced interstitial cystitis. Further study on the NOS and AQP-3 in bladder is needed for clinical application.
Abstract
Purpose: The expression of Nitric oxide Synthase (NOS) and aquaporin (AQP) water channels in rat bladder is recently reported. The aim of this study is to evaluate the expression of inducible NOS (iNOS), aquaporin-3 (AQP-3) in cyclophosphamide (CYP) induced rat bladder. Materials and Methods: The 32 Sprague-Dawley rats were divided into cystitis group (n=20) and control group (n=12). In cystitis group, 100mg/kg CYP was injected every second day for 1 week whereas in control group, normal saline was injected. After extracting of the bladder and dividing dome, body and trigone of the bladder, independently H&E staining and immunohistochemical staining for iNOS and AQP-3 were performed. Expressions of iNOS and AQP-3 were analyzed with a confocal laser scanning microscope and an image analyzer. Results: The expression of iNOS significantly increased in the mucosa, submucosa layer of dome in cystitis group (p<0.05).The expression of AQP-3 significantly increased in the mucosa, submucosa, vessel layer of dome in cystitis group (p<0.05). Conclusions: These results suggest that inflammatory change activates NOS and AQP-3 expression in the bladder tissue of rats. These may imply that NOS and AQP-3 have a pathophyiological role in the cyclophophamide induced interstitial cystitis. Further study on the NOS and AQP-3 in bladder is needed for clinical application.
참고문헌 (32)
- Moutzouris DA, "Interstitial cystitis: an unsolved enigma", Clin J Am Soc Nephrol, 4, pp.1844~1857 (2009)
- Mcmahon SB, "A model for the study of visceral pain states: chronic inflammation of the chronic decerebrate rat urinary bladder by irritant chemicals", Pain, 28, pp.109~127 (1987)
- Berkley KJ, "Behavioral responses to uterine or vaginal distension in the rat", Pain, 61, pp.121~131 (1995)
- Lanteri-Minet M, "Cyclophophamide cystitis as a model of visceral pain in rats: model elaboration and spinal structures involved as revealed by the expression of c-Fos and Krox-24 proteins", Exp Brain Res, 105, pp.220~232 (1995)
- Fraiser LH, "Cyclophosphamide toxicity. Characterising and avoiding the problem", Drugs, 42, pp.781~795 (1991)
- Ho MH, "Physiologic role of nitric oxide and nitric oxide synthase in female lower urinary tract", Curr Opin Obstet Gynecol, 16, pp.423~429 (2004)
- Bennett BC, "Neural control of urethral outlet activity in vivo: role of nitric oxide", J Urol, 153, pp.2004~2009 (1995)
- Hallen K, "Nerve-induced release of nitric oxide from the rabbit corpus cavernosum is modulated by cyclic guanosin 3’,5’-monophosphate", Neuroscience, 133, pp.169~174 (2005)
- Krane CM, "Comparative functional analysis of aquaporins", glyceroporins in mammals and anurans, 2007, pp.18, 452~462
- Spector DA, "Expression, localization, and regulation of aquaporin-1 to-3 in rat urothelia", Am J Physiol Renal Physiol, 282, pp.1034~1042 (2002)
- Sant GR, "The mast cell in interstitial cystitis: Role in pathophysiology and pathogenesis", Urology, 69, pp.34~40 (2007)
- Bon K, "Characterization of cyclophosphamide cystitis, a model of visceral and referred pain, in the mouse:species and strain differences", J Urol, 170, pp.1008~1012 (2003)
- Grinberg-Funes DJ, "The use of prostaglandin F2 alpha for the prophylaxis of cyclophosphamide induced cystitis in rats", J Urol, 144, pp.1500~1504 (1990)
- Ahluwalia A, "Characterization of the capsaicin- sensitive component of cyclophosphamide-induced inflammation in the rat urinary bladder", Br J Pharmacol, 111, pp.1017~1022 (1994)
- Alfieri AB, "Nitric oxide synthases and cyclophosphamide-induced cystitis in rats", Naunyn Schmiedebergs Arch Pharmacol, 363, pp.353~357 (2001)
- Helliwell RJ, "Capsaicin sensitivity is associated with the expression of the vanilloid(capsaicin) receptor (VR1) mRNA in adult rat sensory ganglia", Neurosci Lett, 250, pp.177~180 (1998)
- Vizzard MA, "Up-regulation of pituitary adenylate cyclase-activating polypeptide in urinary bladder pathways after chronic cystitis", J Comp Neurol, 420, pp.355~348 (2000)
- Bouscher M, "Cyclophosphamide-induced cystitis in freely-moving conscious rats: behavioral approach to a new model of visceral pain", J Urol, 164, pp.203~208 (2000)
- Furchgott RF, "The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine", Nature, 288, pp.373~376 (1980)
- Forstermann U, "Isoforms of nitric-oxide synthase: purification and regulation", Methods Enzymol, 233, pp.258~264 (1994)
- Huang A, "The role of nitric oxide in obstructive nephropathy", J Urol, 163, pp.1276~1281 (2000)
- Whittle BJ, "Nitric oxide in physiology and pathology", Histochem J, 27, pp.727~737 (1995)
- Moncada S, "Nitric oxide:physiology, pathophysiology, and pharmacology", Pharmacol Rev, 43, pp.109~142 (1991)
- Smet PJ, "Distribution of nitric oxide synthase-immunoreactive nerves and identification of the cellular targets of nitric oxide in guinea-pig and human urinary bladder by cGMP immunohistochemistry", Neuroscience, 71, pp.337~348 (1996)
- Austin PF, "Lipopolysaccharide and inflammatory cytokines cause an inducible nitric oxide synthase-dependent bladder smooth muscle fibrotic response", J Urol, 170, pp.645~648 (2003)
- Jezernik K, "Immunohistochemical detection of apoptosis, proliferation and inducible nitric oxide synthase in rat urothelium damaged by cyclophosphamide treatment", Cell Biol Int, 27, pp.863~869 (2003)
- Logadottir YR, "Intravesical nitric oxide production discriminates between classic and nonulcer interstitial cystitis", J Urol, 171, pp.1148~1150 (2004)
- Hosseini A, "Nitric oxide as an objective marker for evaluation of treatment response in patients with classic interstitial cystitis", J Urol, 172, pp.2261~2265 (2004)
- Denker BM, "Identification, purification and partial characterization of a novel Mr 28,000 integral membrane protein from erythrocytes and renal tubules", J Biol Chem, 263, pp.15634~15642 (1988)
- 김선옥, "Changes in Aquaporin 1 Expression in Rat Urinary Bladder after Partial Bladder Outlet Obstruction: Preliminary Report", Korean Journal of Urology, 51(4), pp.281~286 (2010), 대한비뇨기과학회
- Rubenwolf PC, "Expression and Localisation of Aquaporin Water Channels in Human Urothelium In Situ and In Vitro", Eur Urol, 56, pp.1013~1024 (2009)
- Fu D, "The structural basis of water permeation and proton exclusion in aquaporins", Mol Membr Biol, 24, pp.366~374 (2007)