Global analysis of gene expression profiles in bladder with persistent detrusor overactivity in a modified bladder outlet obstruction and deligation rat model using cDNA microarrays

초록

Introduction & Objectives The pathophysiological role of persistent detrusor overactivity (PDO) after de-obstructed surgery in patients with benign prostatic hyperplasia remains poorly understood. Recently, we developed a modified method of partial bladder outlet obstruction (mBOO) to be able to deligate without abdominal opening and observe under the similar physiologic condition to obstructed one. In this study, we investigated the alterations of gene expression profiles in mBOO and deligated rat models by microarray. Material & Methods To observe the DO objectively, awake cystometry was performed on the fifty female Sprague-Dawley rats with simultaneous registration of intravesical and intra-abdominal pressure: sham operation (n=10, two weeks), BOO (n=10, two weeks), PDO+ deligated 1 week after BOO during 2 weeks (n=12), PDO- (n=18). The bladders from BOO (n=6), PDO+ (n=6), PDO- (n=6) groups were compared with that from sham group using cDNA microarrays consisting of 14,522 rat genes. Results The ratio of bladder weight (mg) to body weight (g) were significantly higher in the other four groups compared to the sham group (p<0.0001). Deligated bladders showed no decreased bladder weight, comparing to obstructed bladder. DO was found in 90% of BOO group and 40 % of deligated groups (PDO+), and not in the other groups. The bladders from PDO+ showed significantly increased bladder weight, comparing to those from PDO- (p<0.01). Through the clustering analysis of gene expression profiles, marked changes in gene expression in the bladders from mBOO (3,809 genes), PDO + (217 genes), PDO- (7,497 genes) groups were observed for 11,523 genes (two fold up-regulated- 4,515, two fold down-regulated- 7,008), comparing to sham group (Table 1). Table 1. Total gene numbers of 2-fold changed expression levels Groups 2-fold over 2-fold down Total BDO + 145 72 217 BOO 898 2,911 3,809 BDO - 3,472 4,025 7,497