| Objective:The experiment is intended to build the rabbit animal model of low compliance bladder by the way of obstructing bladder outlet and observe the changing of bladder weight, detrusor leak point pressure, compliance,bladder wall Organizational structure and growth factor expression after obstruction. We intend to study the pathophysiological mechanisms of development. And to explore the effect and the mechanism of Doxazosin on Bladder Compliance in bladder outlet obstruction rabbit.We look forward to finding appropriate intervention point to relief the change of bladder wall fibrosis, protecting the bladder compliance.Methods:A total of 40 New Zealand white male rabbits were randomly divided into 4 groups. Every group has 10 rabbits. Partial bladder outlet obstruction was built in group B and C, while group A and group D underwent same operation but no partial bladder outlet obstruction。The main steps:Male rabbits were weighted,anesthetized and fixed on the operation table with supine position. The bladder was catherized transurethrally with 8Fr Foley catheter from penis. The bladder and vesical neck were expose and prepared through a mid-line incision right above the symphysis pubis. A 2-0 silk ligatured loosely around the vesical neck and the 8Fr Foley catheter. The tie just allowed a tip of Venturi hemostatic clamp put in or catheter moved.The next day of the operation, groups C and D received oral administration doxazosin. After 14 weeks, urodynamic examinations were carried out in all groups. The bladder was weighted after cystometry. HE staining, light microscope observing structure of smooth muscle and fibrous connective tissue change.IHC immunohistochemistry, observing bladder smooth muscle CD31,bFGF,TGF-β1 expression.Selecting five field in each photograph under x400 high power field,measuring vessel density and bFGF,TGF-β1 optical density of positive cells. ResultsBladder weight:The bladder weight of group B(14.1±2.3) g and group C (5.0±2.0) g increased significantly than group A and group D (P<0.01);group B increased significantly than group C (P<0.01);group A (3.2±0.9) g and group D (2.9±0.5) g were no obvious difference (P>0.05).Detrusor leak-point pressure:group B (18.8±6.1 cm H2O) show significantly higher than group A,group D (P<0.01) and group C (P<0.05), there were no obvious difference among group A(10.2±2.5 cm H2O),group C(13.5±4.7 cm H2O) and group D(11.6±3.6 cm H2O)(P>0.05)Bladder Compliance:The bladder compliance was significant decreased in group B (1.22±0.39 ml/cmH20) than group A and group D (P<0.01), The bladder compliance in group C (4.25±2.19 ml/cmH2O) was significantly higher than group A and group D (P<0.05);group A(2.86±0.56 ml/cmH2O) and group D (2.90±0.53 ml/cmH2O) were no obvious difference (P>0.05)After 14 weeks of bladder outlet obstruction, bladder structure and function altered significantly,bladder weight increased significantly, bladder wall obvious accumulation, bladder wall trabeculation were seen, yellow calculus could be seen occasionally in the bladder,urine turbidity;bladder capacity significantly increased in group C, urine clear than the obstruction group, and no calculus formation, one case was found that associated with bladder diverticulum.There were no ureterectasia and uronephrosis in All animals.measured vascular density between the smooth muscle by CD31 expression.It was significant decreased in group B (25.07±1.75)/mm2 than group A,group D and group C(P<0.01); group C (32.58±1.35)/mm2 was significantly decreased than group A and group D (P<0.01);group A and group Dwere no obvious difference (P=0.242>0.05)bFGF positive cell optical density (optical density; OD):group B (0.2502±0.0489) show significantly higher than group A,group Dand group C (P<0.01) group C (0.1029±0.026) show significantly higher than group A,group D (P< 0.01);there were no obvious difference among group A,group D (P>0.05) TGF-β1 positive cell optical density (optical density; OD):group B (0.1996±0.0377) show significantly higher than group C (0.0784±0.0224) (P<0.01) TGF-β1 was no expression in group A and group D, Optical density can not be determined.Conclusions1 After BOO, the bladder outlet resistance increases, the bladder pressure continued to increase, leading to the bladder wall ischemia, growth factors bFGF, TGF-β1 expression was increased, resulting in increased collagen deposition, the percentage of fibrous connective tissue was increased,bladder wall remolding, causing the bladder fibrosis, bladder wall obvious accumulation, bladder weight increased significantly, loss of normal bladder toughness, so that the normal bladder turn into a small volume, high pressure, low compliance bladder.2 Early taking doxazosin after bladder outlet obstruction can be improved bladder blood flow, reducing bFGF, TGF-β1 expression of growth factors, thereby reducing the degree of bladder fibrosis, delayed damage to bladder compliance, protecting bladder storage function. protecting renal function by Reducing the detrusor leak point pressure. |
