DMSO Improve The Protamine Sulfate Induced Rat Cystitis By Reducing Inflammation And Oxidative Stress

Background and Aims:Bladder pain syndrome/interstitial cystitis(BPS/IC) is a sterile bladder condition manifested as suprapubic and/or bladder pain related to bladder filling, accompanied by urinary frequency and urgency. In United States adult females,BPS/IC symptoms are widespread, distrrubing 3.3–7.9 million women. Besides, quality of life and social interaction in BPS/IC patients suffered a serious impact. At present, the pathogenesis of BPS/IC is stll unclear. Many theories have been suggested to exemplify the pathogenesis of BPS/IC, such as epithelial damage, mast cell infiltration, autoimmunity, infection, and pelvic floor dysfunction. However, inflammation has been confirmed as an irreplaceable role of in both human and animal BPS/IC.At present,the bladder infusion drugs(DMSO, Cystistat) treatment with BPS / IC is more efficient means and methods, but the use of DMSO in China has not yet been. Studies have shown that BPS/IC bladder tissue excess of inflammatory mediators such as IL-6, TNF-a and other expression, suggesting that the inflammatory response involved in the occurrence of the disease. Dimethyl sulfoxide(DMSO) is a colorless organic solvent, having a good permeability. Currently,many study found that DMOS has a strong interference free radical generation, removal of the generated free radicals, reduce inflammatory mediators and cytokines, play a role in anti-inflammatory and oxidative stress response. Accordingly, IC model induced by protamine sulfate(protamine sulfate, PS) which used it to investigate the dimethyl sulfoxide treatment mechanisms fo protamine sulfate-induced rat bladder inflammation.Methods:In the first part, Animal model establishment with protamine sulfate-induced cystitis and HE and toluidine blue staining were applied evaluation the histological score and mast cell count in each protamine sulfate-induced rat cystitis groups. 48 female SD rats weighing 200-230 g were randomized into normal,Protamine sulfate(PS) perfusion group,DMSO perfusion group(group PS+DMSO), saline perfusion group(NS group), 12 rats in each group. In the normal group, a PE-50 transurethral catheter was inserted into the bladder to empty the bladder, and then, 0.5 mL of saline was infused intravesically and remained for 30 min. In the PS group, the bladders were pretreated with 0.5 mL of PS(30 mg/mL, sigma, P3369) by intravesical infusion, the DMSO group,0.5ml 50%DMSO treat with bladder perfusion and keep its 30min; the PS+DMSO group(PS dissolved in 50%DMSO) 0.5ml 30mg/ml treat with bladder perfusion and keep its 30min; After four weeks, HE and toluidine blue staining were applied evaluation the histological score and mast cell count in each groups.In the second part, western blot were used confirmed the expression of SOD2, GSH-Px, IL-6, IL-1B, TNF- αproteins expression in each protamine sulfate-induced rat cystitis groups.In the third part, We investigate the efficacy of DMSO in protamine sulfate-induced rat cystitis using cystometry and muscle strips study.Main result1. Using protamine sulfate protein in rat bladder perfusion success analog a rat model of Bladder pain syndrome/interstitial cystitis2. Rat bladder performance that bladder mucosa and lamina propria showed hemorrhage and edema, a large area of epithelial shedding, a large number of mast cell infiltration, inflammation scores were significantly increased after PS intravesical, but the PS + DMSO treated group showed more complete epithelial tissue, mast cell infiltration reduced, inflammation scores were significantly decreased.The study results suggest that DMSO play a protective role in cystitis rats.3. Compared with NS and PS group, PS+DMSO group rat bladder inflammatory cytokines(IL-6、IL-1B、TNF-α) significantly decreased and antioxidative enzyme is significantly increased. bladder function and muscle contraction frequency is significantly improved.Conclusions:1. We confirmed that inflammation and oxidative stress involved in the pathophysiology of protamine sulfate-induced cystitis.2. MDSO by reducing oxidative stress and inflammation improve protamine sulfate induced cystitis.