Long-term Aspirin Administration Suppresses Inflammation In Diabetic Cystopathy

Objective: Diabetic cystopathy(DCP)is one of the most common and troublesome urinary complications of diabetes mellitus.The etiology and molecular mechanism are still unclear,and there are strong and obvious drug resistance and adverse reactions in various drug treatments.Therefore,defining a therapeutic approach to study the time effects of the inflammatory response and to explore new therapeutic strategies is critical for patients with DCP.Aspirin has shown impressive potential in the treatment of cardiovascular events and other complications of diabetes.This dissertation endeavors to evaluate the interaction between long-term oral aspirin treatment and inflammatory progression and disease duration,and to explore the therapeutic potential of aspirin on DCP using streptozotocin(STZ)-induced type 1diabetes.Methods: In this 12-week study,48 male Sprague-Dawley rats were randomly assigned to four groups: negative control(NC),NC treated with aspirin(NC+Aspirin),DCP,and DCP treated with aspirin(DCP+Aspirin).The animal model of DCP was established by intraperitoneal injection of STZ(65mg/kg).Hematoxylin-eosin(H&E)and Masson staining were performed to observe the histopathological manifestations of the bladder.Pathological changes of bladder ultrastructure observed by transmission electron microscopy(TEM).The expression of nuclear factor kappa B(NF-κB),tumor necrosis factor-alpha(TNF-α),interleukin(IL)-6,and IL-1β in bladder detrusor smooth muscle(DSM)was analyzed using quantitative reverse transcription-polymerase chain reaction(q RT-PCR),Western blot and immunohistochemistry(IHC)analysis.Results: Aspirin ameliorated pathological weight loss and bladder weight increase in diabetic rats,accompanied by an approximately 16.5% decrease in blood glucose concentrations after 10 weeks treatment compared to the DCP group.H&E,Masson,IHC and TEM revealed that a dilated bladder with thickened DSM layer,inflammatory infiltration,fibrosis and ultrastructural damage were observed in diabetic rats,which were partially restored by aspirin.The expression of inflammatory mediators was further determined by q RT-PCR and Western blot after 4,7 and 10 weeks of continued treatment.Thorough investigation revealed inflammation gradually increased as the disease progresses and long-term oral aspirin effectively suppressed the expression of TNF-α(P< 0.01),IL-1β(P < 0.01),IL-6(P < 0.01),and NF-κB(P < 0.01)in DSM tissues compared with untreated diabetic rats.Conclusions: Aspirin could ameliorate the pathological damage of bladder tissue in diabetic cystopathy.Long-term aspirin administration has a therapeutic effect on bladder detrusor smooth muscle(DSM)by down-regulating the expression of inflammatory cytokines.The study provided a revealing insight into the theoretical basis for the longterm medication therapies,indicating that aspirin might serve as a potential strategy for DCP treatment.