AKINO Hironobu 福井大学, 医学部, 准教授 (90159335)
AOKI Yoshitaka 福井大学, 医学部, 助教 (30273006)
YOKOTA Yoshifumi 福井大学, 医学部, 教授 (50222386)
KUSUKAWA Naoya 福井大学, 医学部, 医員 (80372499)
伊藤 秀明 福井大学, 医学部, 助教 (00345620)
棚瀬 和弥 福井大学, 医学部附属病院, 助教 (00359720)
|Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2010: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2008: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
We investigated the relationship between polymorphism of metabolic syndrome-related gene and occurrence of lower urinary tract symptoms, using human blood samples and animal pathological models.
Organ ischemia is thought to be caused by matrix digestion by metalloproteinases (MMPs) leading to rupture of atherosclerotic plaques. Production of macrophage MMP-2 and MMP-9 is induced by cycloxygenase-2 (COX-2) and prostaglandin E2 (PGE2) synthesis. The-765G->C polymorphism of the COX-2 gene has been reported to associate with a decrease risk of myocardial infarction and stroke. Detection of this genotype may be useful to predicting genetic risk of bladder storage dysfunction because bladder ischemia is known as one of the important risks for lower urinary tract symptoms (CUTS). Using blood samples of patients with overactive bladder (OAB), the-765G->Cvariant was genotyped. As the prevalence of the variant was low in these patients, the significant relationship was not found. Next, to investi
gate the association between the urinary levels of PGE2, PGF2α, nerve growth factor (NGF) and substance P, and OAB symptoms, urine samples from 114 patients in the chronic phase of a brain disease and 27 healthy controls were analyzed by enzyme-linked immunosorbent assay. As a result, the urinary PGE2 level was putatively elevated in patients with suprapontine brain diseases and associated with the presence of OAB. We collected data on 28,238 individuals (9,286 males and 18,952 females) who participated in a multiphasic health screening in Fukui, Japan. The overall prevalence of nocturia (defined as two or more voids/night) was 5.8%. In the multivariate analysis, a significant association was found between nocturia and the followings:age, male gender, BMI<18.5, BMI>27.0, high blood pressure and impaired glucose tolerance. The number of components of MetS was correlated with nocturia.
Using rat animal models with cerebral infarction (CI), we investigated the underlying mechanism of increase in the urinary PGE2 level in patients with suprapontine brain diseases. The ATP amount in the bladder of CI rats was 2.24 times larger than that of sham operated(SO) rats 6 hours after CI. Compared with SO rats, the mRNA expression of P2X3, ASIC2, TRPV1, M2 and M3 in the bladder wall increased after CI, meaning upregulation of C fiber afferent nerves of the bladder. These changes were not found in rats pretreated with resiniferatoxin.
As an animal model of metabolic syndrome, rats were fed with fructose-rich diet for 11 months. Rats revealed hypertension, glucose intolerance, and frequent voiding. The expression of COX-2 in the bladder wall was found to increase in these rats. Less