Identification and suppression of specific genes of urinary incontinence using RNAi

利用 RNAi 识别和抑制尿失禁的特定基因

基本信息

  • 批准号:
    16390461
  • 负责人:
  • 金额:
    $ 8.13万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    2004
  • 资助国家:
    日本
  • 起止时间:
    2004 至 2005
  • 项目状态:
    已结题

项目摘要

Development of bladder overactivity (BO) caused by cerebral infarction (CI) is believed to require RNA transcription in the pontine micturition center (PMC). We previously reported that the expression of cyclooxygenase-2 (COX-2) mRNA was mediated by the activity of an NMDA (N-methyl-D-aspartate) receptor in the PMC and necessary for the development of BO. This study was undertaken to examine whether the expression of prostaglandin (PG) E or D synthase, downstream gene of COX-2, and levels of PGE2 and D were related to BO. To begin with, background mouse (C57-BL/6J) of COX-2 knockout was used to examine whether it has the same response to CI as a rat model. To confirm that the expression of COX-2 is essential for the development of BO, in vivo RNAi in the mice PMC and left middle cerebral artery (MCA) occlusion are thought to be necessary.Methods : Cerebral infarction (CI) was induced by MCA occlusion in female SD rats and C57-BL/6J mice. Awake animals were cystometrically examined. Spe … More cimens were obtained from the dorsal pontine tegmentum (DPT) 0.25, 1, 3, 5, 12, and 24 hours after MCA occlusion or a sham operation (SO). Expressions of PGES and PGDS in the DPT were monitored with real-time PCR. To determine whether PGE2 is essential for the induction of BO, microinjection of PGE2 into the PMC or periaquaeductal gray (PAG) was performed in urethane anesthetized rats. Furthermore, ONO-8711, EP1 receptor antagonist was administered intravenously or intracerebroventriculaly before PGE2 instillation.Results : Bladder capacity of CI rats and mice was significantly reduced 1-24 hours after MCA occlusion. One hour after MCA occlusion, PGES and PGDS mRNA expression had significantly increased, as compared to that in SO animals. PGES expressions remained consistently higher than those in SO rats at least 12 hours after MCA occlusion. Pretreatment with MK-801 inhibited the development of bladder overactivity and significantly reduced the expression of PGES mRNA in the DPT. The level of PGE2 increased 3 to 5 hours after MCA occlusion at the DPT. Microinjection of PGE2 into the cerebral ventricle and dorsal pontine tegmentum increased bladder capacity. PGE2 into the PAG significantly decreased bladder capacity, which was antagonized by the administration of ONO-8711. MCA occlusion produced a significant reduction in bladder capacity and increased expression of COX-2/PGES in the DPT of C57-BL/6J mice.Conclusion : These results indicate that the development of BO following MCA occlusion is mediated by an increase in COX-2 and PGES mRNA expression in the DPT. Increase in PGE2 level in the PAG is believed to play an important role in the development of BO caused by CI. Less
脑梗塞(CI)引起的膀胱过度活动(BO)被认为需要脑桥排尿中心(PMC)的RNA转录。我们先前报道,环氧合酶-2(COX-2)mRNA的表达是由PMC中N-甲基-D-天冬氨酸(NMDA)受体的活性介导的,是BO发生所必需的。本研究旨在探讨前列腺素(PG)E或D合成酶、COX-2下游基因的表达以及PGE2和D水平与BO的关系。首先,用COX-2基因敲除的背景小鼠(C57-BL/6J)检测其对脑缺血的反应是否与大鼠模型相同。为了证实COX-2的表达在BO的发生发展中起重要作用,有必要在小鼠PMC和左侧大脑中动脉(MCA)闭塞的小鼠体内进行RNAi。方法:采用雌性SD大鼠和C57-BL/6J小鼠大脑中动脉闭塞诱导脑梗塞。清醒的动物接受膀胱计量学检查。固相萃取…大脑中动脉阻塞或假手术(SO)后0.25、1、3、5、12、24小时,脑桥背侧被盖(DPT)的胞核数量增多。用实时荧光定量聚合酶链式反应(Real-Time-PCR)检测DPT中PGES和PGDS的表达。在乌拉坦麻醉大鼠的PMC或导水管周围灰质(PAG)内微量注射PGE2,以确定PGE2是否在BO的诱导中起重要作用。结果:脑梗塞大鼠和小鼠在大脑中动脉结扎后1~24小时,膀胱容量明显减少。与假手术组相比,大脑中动脉结扎后1h,PGES和PGDS基因的表达显著增加。在大脑中动脉闭塞后至少12小时,PGES的表达持续高于SO大鼠。MK-801可抑制大鼠膀胱过度活动的形成,并显著降低DPT中PGES基因的表达。在DPT处,大脑中动脉结扎后3~5小时PGE2水平升高。脑室和桥脑背侧被盖内微量注射前列腺素E_2可增加膀胱容量。进入PAG的PGE2显著降低膀胱容量,ONO-8711可拮抗这一作用。C57-BL/6J小鼠大脑中动脉阻塞后,DPT中COX-2/PGES的表达增加,膀胱容量明显减少。结论:C57-BL/6J小鼠DPT中COX-2和PGES的表达增加是导致BO发生的重要机制之一。PAG中PGE2水平的升高在CI所致BO的发生发展中起重要作用。较少

项目成果

期刊论文数量(17)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
蓄尿症状発生のメカニズム-中枢神経系を中心に-
储尿症状的机制 - 关注中枢神经系统 -
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Yokoyama O;Mita E;Akino H;Tanase K;Ishida H;Namiki M;横山 修
  • 通讯作者:
    横山 修
Effects of tolterodine on an overactive bladder depend on suppression of C-fiber bladder afferent activity in rats
  • DOI:
    10.1097/01.ju.0000176793.50410.9e
  • 发表时间:
    2005-11-01
  • 期刊:
  • 影响因子:
    6.6
  • 作者:
    Yokoyama, O;Yusup, A;Akino, H
  • 通讯作者:
    Akino, H
Pathophysiology and treatment of the overactive bladder.
膀胱过度活动症的病理生理学和治疗。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Yotsuyanagi S;Yokoyama O;Komatsu K;Kodama K;Nagasaka Y;Namiki M;Yokoyama O
  • 通讯作者:
    Yokoyama O
Id2 haploinsufficiency in mice leads to congenital hydronephrosis resembling that in humans
  • DOI:
    10.1111/j.1365-2443.2004.00805.x
  • 发表时间:
    2004-12-01
  • 期刊:
  • 影响因子:
    2.1
  • 作者:
    Aoki, Y;Mori, S;Yokota, Y
  • 通讯作者:
    Yokota, Y
Prognostic value of nuclear area index in patients with bladder cancer.
核面积指数对膀胱癌患者的预后价值
  • DOI:
  • 发表时间:
    2004
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Yokoyama O;Mita E;Akino H;Tanase K;Ishida H;Namiki M;Yusup A
  • 通讯作者:
    Yusup A
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YOKOYAMA Osamu其他文献

YOKOYAMA Osamu的其他文献

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{{ truncateString('YOKOYAMA Osamu', 18)}}的其他基金

Interdisciplinary study of neural circuit mechanisms of spatial attention
空间注意神经回路机制的跨学科研究
  • 批准号:
    15K16016
  • 财政年份:
    2015
  • 资助金额:
    $ 8.13万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Roles of prefrontal cortex and basal ganglia in decision making based on preference
前额叶皮层和基底神经节在基于偏好的决策中的作用
  • 批准号:
    23700504
  • 财政年份:
    2011
  • 资助金额:
    $ 8.13万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Does prevention of metabolic syndrome lead to improvement of erectile dysfunction or lower urinary tract symptoms?
预防代谢综合征是否可以改善勃起功能障碍或下尿路症状?
  • 批准号:
    21659370
  • 财政年份:
    2009
  • 资助金额:
    $ 8.13万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Does polymorphism of metabolic syndrome-related genes induce lower urinary tract symptoms?
代谢综合征相关基因多态性是否会诱发下尿路症状?
  • 批准号:
    20390422
  • 财政年份:
    2008
  • 资助金额:
    $ 8.13万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Single nucleotide polymorphism (SNP) in COX-2 promoter gene:roles in the prevention of overactive bladder caused by cerebro-vascular accident or bladder outlet obstruction
COX-2启动子基因单核苷酸多态性(SNP)在预防脑血管意外或膀胱出口梗阻引起的膀胱过度活动症中的作用
  • 批准号:
    18390433
  • 财政年份:
    2006
  • 资助金额:
    $ 8.13万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Functional analysis of specific genes of urinary incontinence in the pontine micturition center
脑桥排尿中枢尿失禁特异性基因的功能分析
  • 批准号:
    14370507
  • 财政年份:
    2002
  • 资助金额:
    $ 8.13万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Signal transdaction and gene expression in the pors associated with the overactive bladder following cerebra-vascular disease
脑血管疾病后膀胱过度活动症相关的信号转导和基因表达
  • 批准号:
    12470331
  • 财政年份:
    2000
  • 资助金额:
    $ 8.13万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Central muscarinic mechanisms of bladder overactivity associated with Alzheimer type senile dementia.
与阿尔茨海默型老年痴呆相关的膀胱过度活动的中枢毒蕈碱机制。
  • 批准号:
    10470334
  • 财政年份:
    1998
  • 资助金额:
    $ 8.13万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)

相似海外基金

Elucidation of endogenous factors of stress urinary incontinence in LOXL1 gene-deficient rats
LOXL1基因缺陷大鼠压力性尿失禁的内源性因素的阐明
  • 批准号:
    20K22769
  • 财政年份:
    2020
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    $ 8.13万
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Regenerative therapy for stress urinary incontinence and pelvic floor disorder
压力性尿失禁和盆底疾病的再生疗法
  • 批准号:
    10370405
  • 财政年份:
    2020
  • 资助金额:
    $ 8.13万
  • 项目类别:
Regenerative therapy for stress urinary incontinence and pelvic floor disorder
压力性尿失禁和盆底疾病的再生疗法
  • 批准号:
    10600104
  • 财政年份:
    2020
  • 资助金额:
    $ 8.13万
  • 项目类别:
Targeted Regenerative Therapy For Urinary Incontinence
尿失禁的靶向再生治疗
  • 批准号:
    10019164
  • 财政年份:
    2019
  • 资助金额:
    $ 8.13万
  • 项目类别:
Phenotrypes and Mechanisms of Urinary Incontinence in Obesity/pre-Type 2 Diabetes
肥胖/2 型糖尿病前期的尿失禁表型和机制
  • 批准号:
    9160437
  • 财政年份:
    2016
  • 资助金额:
    $ 8.13万
  • 项目类别:
Phenotrypes and Mechanisms of Urinary Incontinence in Obesity/pre-Type 2 Diabetes
肥胖/2 型糖尿病前期的尿失禁表型和机制
  • 批准号:
    9754115
  • 财政年份:
    2016
  • 资助金额:
    $ 8.13万
  • 项目类别:
Therapy for Obesity-associated Stress Urinary Incontinence
肥胖相关压力性尿失禁的治疗
  • 批准号:
    9107289
  • 财政年份:
    2016
  • 资助金额:
    $ 8.13万
  • 项目类别:
Stem Cell Therapy Combined with Growth Factors for Stress Urinary Incontinence
干细胞疗法联合生长因子治疗压力性尿失禁
  • 批准号:
    8915847
  • 财政年份:
    2014
  • 资助金额:
    $ 8.13万
  • 项目类别:
Tissue recovery in the pathophysiology of stress urinary incontinence
压力性尿失禁病理生理学中的组织恢复
  • 批准号:
    8586881
  • 财政年份:
    2011
  • 资助金额:
    $ 8.13万
  • 项目类别:
Tissue recovery in the pathophysiology of stress urinary incontinence
压力性尿失禁病理生理学中的组织恢复
  • 批准号:
    8372403
  • 财政年份:
    2011
  • 资助金额:
    $ 8.13万
  • 项目类别:
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