MOLECULAR MECHANISM FEMALE STRESS URINARY INCONTINENCE

描述(改编自申请人的摘要)：过去1和 一年半以来，在授予1 R55DK51374的支持下，我们已经修改和测试了 建立可复制的雌性大鼠动物模型的可行性 压力性尿失禁。我们已经研究了怀孕的影响和 可控机制的超微结构和功能的传递。 我们还通过使用怀孕的大鼠来修改我们的模型，并在 牵引下的阴道内气囊将力引向提升器 和会阴来模拟人类的情况。我们掌握的信息 得到了我们的观点的强烈支持，那就是 老鼠与人类相似。因此，我们建议研究 女性应激发病的分子机制 尿失禁。 我们假设出生创伤、激素缺乏(更年期)和 衰老对几种生长因子基因和蛋白表达的影响 (胰岛素样生长因子系统、成纤维细胞生长因子、神经生长因子、转化生长因子、血小板衍生生长因子)和受体(肾上腺素能、毒扁豆碱 和雌激素)，这反过来又改变了 可控机制。该假设将通过完成 以下是具体目标： 1.研究和比较功能、超微结构、细胞和 可控机制的分子变化a)。在怀孕期间和 在自然分娩之后，b)在催产素诱导分娩之后，以及c) 剖腹产后分娩。 2.功能、超微结构、细胞和分子检测 反复产伤后排尿机制的变化。 3.功能、超微结构、细胞和分子检测 模拟产伤后排尿机制的变化及意义 双侧卵巢切除术。 4.功能、超微结构、细胞和分子的测定 联合模拟分娩后排便机制的变化 创伤、卵巢切除和衰老。

DESCRIPTION (Adapted from the Applicant's Abstract): In the past 1 and 1/2 years, supported by grant 1 R55DK51374, we have modified and tested the feasibility of developing a reproducible rat model to study female stress urinary incontinence. We have studied the effect of pregnancy and delivery on the ultrastructure and function of the continence mechanism. We also modified our model by using pregnant rats and placed a intravaginal balloon under traction to direct the force to the levators and perineum to simulate the human situation. The information we have gained strongly support our opinion that the continence mechanism in the rats is similar to that of humans. We therefore propose to study the molecular mechanism involved in the pathogenesis of female stress urinary incontinence. We hypothesize that birth trauma, hormonal deficiency (menopause) and old age affect the gene and protein expression of several growth factors (IGF system, FGF, NGF, TGF, PDGF) and receptors (adrenergic, muscarinic and estrogen) which in turn change the structure and function of the continence mechanism. The hypothesis will be tested by completing the following specific aims: 1. To study and compare the functional, ultrastructural, cellular and molecular changes of the continence mechanism a). during pregnancy and after spontaneous delivery, b) after oxytocin-induced delivery and c) after delivery by cesarean section. 2. To examine the functional, ultrastructural, cellular and molecular changes of the continence mechanism after repeated birth trauma. 3. To examine the functional, ultrastructural, cellular and molecular changes of the continence mechanism after simulated birth trauma and bilateral ovariectomy. 4. To determine the functional, ultrastructural, cellular and molecular changes of the continence mechanism after combined simulated birth trauma, ovariectomy and aging.