Ultrastructural Alterations of Mitochondria and Mitochondrial DNA Mutations of the Human etrusor After Partial Bladder Outlet Obstruction

• Main Authors: Shing-Hwa Lu, 盧星華
• Other Authors: Yau-Huei Wei
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/88709820237912787777

博士 === 國立陽明大學 === 臨床醫學研究所 === 88 === This study was designed to investigate the ultrastructural changes of mitochondria and mitochondrial DNA (mtDNA) mutations in human detrusor after partial bladder outlet obstruction (BOO). The correlation of these data with the results of urodynamic analysis was also studied. Fifty-two and sixty-two male patients with or without BOO were respectively enrolled in the ultrastructural study of mitochondria and the subsequent study of mtDNA mutations in the detrusor. The patients were assessed by international prostate symptom score (IPSS), quality of life assessment index (QoL) and sonography. The severity of partial BOO was determined by the urodynamic analysis with pressure-flow study and the pressure-flow data were plotted on the ICS-nomogram (international continence society-nomogram) and linPURR (linear passive urethral resistance relation) nomogram. In the first part of study, random detrusor biopsies obtained cystoscopically were fixed immediately and processed for transmission electron microscopic observation. Random areas were photographed for further morphological and morphometric analyses using mitochondrial damage score and stereological principles. Finally, We compared the ultrastructural data with urodynamic results statistically. In the second part of study, random detrusor biopsies obtained cystoscopically were analyzed by polymerase chain reaction (PCR) techniques to detect possible mtDNA deletions. Primer-shift PCR and DNA sequencing were then performed to characterize specific mtDNA deletion. A semi-quantitative PCR method was used to determine the proportion of the deleted mtDNA in detrusor. At last, the mtDNA deletion and the urodynamic results were compared statistically. In the first part of study, mitochondrial damage score and the mean volume of the mitochondria were found to correlate strongly with the urodynamic severity of partial BOO. Volume density of the mitochondria, surface density of the mitochondrial outer membrane and mitochondrial number per unit area of cytoplasm were not significantly correlated with the severity of partial BOO. In the second part of study, a 4,977 bp mtDNA deletion in the human detrusor was identified. Both the incidence and proportion of mtDNA with the 4,977 bp deletion were increased after partial BOO (P = 0.005 and P = 0.012, respectively). The incidences of the mtDNA deletion were 4.2% (1 of 24) in the non-obstructive group, 27.8% (5 of 18) in the equivocal group, and 40% (8 of 20) in the obstructive group. The mean proportions of the 4,977 bp deleted mtDNA were 23.7 and 12.7 times higher for the patients in the obstructive and equivocal groups, respectively, compared with that of the patients in the unobstructive group. We conclude that the swelling and structural destruction of the detrusor mitochondria were parallel to the severity of partial BOO. In addition, we first disclosed mtDNA with the 4,977 bp deletion in human detrusor and an increase of this mtDNA deletion after partial BOO. These changes might be associated with an impaired mitochondrial function and oxidative metabolism after partial BOO. The damage to the detrusor mitochondria and the increase of mtDNA deletion might account for the voiding dysfunction after partial BOO.