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Effect and the Mechanism Study of Doxazosin on Bladder Compliance in Bladder Outlet Obstruction Rabbit

Author: HuangFuXueJun
Tutor: ZhaoYaoRui
School: Tianjin Medical University
Course: Surgery
Keywords: Bladder outlet obstruction Compliance Doxazosin Vascular density
CLC: R965
Type: Master's thesis
Year: 2011
Downloads: 26
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Abstract

Objective: To establish rabbit bladder partial outlet obstruction model approach to induce low compliance bladder observed partial outlet obstruction of the bladder cause bladder weight reduction compliance, detrusor leak point pressure, compliance and bladder wall structure, growth change factor expression study pathophysiological mechanisms of development and change. And investigate doxazosin (doxazosin) to reduce the impact and mechanisms of bladder outlet obstruction bladder compliance, in order to find the appropriate points of intervention relieve bladder outlet obstruction bladder wall fibrosis progression, to protect bladder compliance. Methods: 40 adult male New Zealand white rabbits were randomly divided into four groups: A 10, B group 10 group of 10, C 10, D group. A sham operation control group, group B partial bladder outlet obstruction group and the sham-operated group C bladder partial outlet obstruction after giving oral doxazosin group, D group after giving oral doxazosin group (C and Group D the next day to give the doxazosin 3mg/kh / day orally). Group B and group C were surgical bladder partial outlet obstruction model, in the same way, the main steps: Weighing rabbit plate fixed after anesthesia, lower abdominal skin preparation, from the insertion of the penis into the No. 8Fr catheter, take suprapubic midline incision into the pelvic cavity, locate the bladder, the free bladder neck to the contralateral, free from the bladder neck margin blunt, since the rear with a 2-0 silk around 8Fr catheter the ligation bladder neck, tightness of the catheter within the urethra move a little tight is appropriate; the control group only free, without ligation groups at 14 weeks after surgery urodynamic testing, rabbits and specimens from bladder specimens, bladder weighing were killed after the tests are complete. Conventional HE staining of the bladder wall smooth muscle, fibrous connective tissue changes; IHC Immunohistochemical detection of bladder smooth muscle tissue CD31, bFGF, TGF-β1 expression level of each picture in the positive expression rich region, selected five high power field, get digital Photo Image pro software, measuring the density of blood vessels, bFGF, TGF-β1 in the line of cells positive reaction optical density value (optical density; OD) was measured in order to quantify the positive expression for statistical analysis. The results: bladder weight: bladder partial outlet obstruction group (14.1 ± 2.3) g, bladder after partial outlet obstruction give oral doxazosin group (5.0 ± 2.0) g were significantly higher than the sham control group and the sham given doxazosin group, significant differences (P lt; 0.01); bladder outlet part of the sub-terrier group to give oral doxazosin group was significantly higher than bladder outlet obstruction, there is a significant difference (P lt; 0.01); sham control group (3.2 ± 0.9) g, sham operation give sandy banks of triazine group (2.9 ± 0.5) g There was no statistical significance (P gt; 0.05). Detrusor leak point pressure: bladder outlet partial obstruction group (18.8 ± 6.1) cmH20 higher than the sham control group (10.2 ± 2.5) cmH2O and sham give doxazosin group (11.6 ± 3.6) cmH2O significant difference (P lt; 0.01), and higher than the bladder partial outlet obstruction give oral doxazosin group (13.5 ± 4.7) cmH2O, was statistically significant (P lt; 0.05); sham-operated group, bladder After partial outlet obstruction give oral doxazosin group given doxazosin in the sham-operated group among the three groups without statistical significance (P gt; 0.05). Bladder compliance: bladder outlet partial obstruction group (1.22 ± 0.39) ml/cmH2O with sham-operated group, sham give sandy banks losartan group was significantly decreased, there is a significant difference (P lt; 0.01); bladder give oral doxazosin group (4.25 ± 2.19) after partial outlet obstruction ml/cmH2O higher than after the sham control group and the sham given doxazosin group was statistically significant (P lt; 0.05): false after ml/cmH2O with the sham surgery control group (2.86 ± 0.56) give the doxazosin group (2.90 ± 0.53) ml/cmH2O not statistically significant (P gt; 0.05). Bladder structure and function after 14 weeks of bladder outlet obstruction occurred significant changes in bladder weight significantly increased bladder wall was thickened bladder wall seen trabeculation the occasional yellow stones in the bladder, urine turbid. Bladder capacity increased significantly obstruction after given doxazosin group after 14 weeks, was a water pouch, urinary the color compared obstruction group cleared, and no stone formation, there is one case associated with bladder diverticulum. All animals found no ureteral dilatation and renal accumulation of water. Light microscopy to 14 weeks after bladder outlet obstruction, detrusor hypertrophy, a significant increase in the infiltration of collagen fibers between the muscle bundles. The obstruction given doxazosin group 14 weeks, the most important performance detrusor hypertrophy. The percentage content of the fibrous connective tissue of the percentage content of the fibrous connective tissue: bladder outlet partial obstruction group (25.03 ± 6.91), sham-operated group, sham give the doxazosin group and bladder partial outlet obstruction, and give them more give sandy doxazosin group (18.29 ± 3.16) was significantly increased, and there is a significant difference (P lt; 0.01); given doxazosin group than in the sham control group and the sham and bladder after partial outlet obstruction terazosin group was statistically significant (P lt; 0.05); sham control group (13.82 ± 3.69) given doxazosin group (13.05 ± 3.94) in the sham-operated two groups was not statistically significant (P = 0.703 gt; 0.05). By the expression of CD31-positive, the vascular smooth muscle between measured density: bladder outlet partial obstruction group (25.07 ± 1.75) / mmm2 significantly less than the sham-operated group, sham operation given after giving the doxazosin group and bladder partial outlet obstruction the doxazosin group (32.58 ± 1.35) / mm2, a significant difference (P lt; 0.01); bladder partial outlet obstruction given the doxazosin group of less than the sham-operated group, sham operation given doxazosin group statistically significant (P lt; 0.01); sham control group (37.39 ± 1.31) / mmm2 and the sham-operated give doxazosin group (38.51 ± 3.29) / mm2 two groups was not statistically significant (P = 0.242 gt; 0.05). bFGF cells positive reaction optical density (optical density; OD): bladder partial outlet obstruction group (0.2502 ± 0.0489) was significantly higher than the sham-operated group, sham operation given after giving the doxazosin group and bladder partial outlet obstruction doxazosin group (0.1029 ± 0.026), a significant difference (P lt; 0.01); give the doxazosin group and bladder after partial outlet obstruction with the sham-operated group, sham operation given doxazosin group higher statistical significance (P lt; 0.01); sham control group (0.0118 ± 0.002) and sham operation given doxazosin group (0.0137 0.009), the two groups was not statistically significant (P gt; 0.05). TGF-β1 cells positive optical density (optical density; OD): bladder partial outlet obstruction group (0.1996 ± 0.0377) was significantly higher than the bladder partial outlet obstruction given doxazosin group (0.0784 ± 0.0224), a significant difference ( P lt; 0.01); TGF-β1 in the sham-operated group and the sham given the sandy banks of triazine group no expression failed line of light density measurement. Conclusion: 1 BOO, bladder outlet resistance increase bladder pressure continued to increase, resulting in ischemia of the bladder wall, the growth factor bFGF, increased expression of TGF-β1, resulting in an increase in collagen deposition, increased percentage of fibrous connective tissue, bladder wall tissue remodeling, causing bladder fibrosis, obvious thickening of the bladder wall, bladder weight significantly increased lost normal bladder toughness, normal bladder into a small-capacity, high-pressure, low-compliance bladder. Early application doxazosin bladder outlet obstruction can improve bladder blood flow, lowering of bFGF, TGF-β1 in the expression of growth factors, thereby reducing the degree of bladder fibrosis, delayed the BOO bladder compliance damage, protect the bladder urine storage function reduce detrusor leak point pressure, protect renal function.

Effect and the Mechanism Study of Doxazosin on Bladder Compliance in Bladder Outlet Obstruction Rabbit

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