MOLECULAR MECHANISM FEMALE STRESS URINARY INCONTINENCE

描述（改编自申请人的摘要）：在过去的1和 1/2年，由赠款1 R55 DK 51374支持，我们已经修改和测试 建立可重复的雌性大鼠模型的可行性 压力性尿失禁我们研究了怀孕的影响， 递送的超微结构和功能的调节机制。 我们还通过使用妊娠大鼠修改了我们的模型，并将 牵引下的阴道内气囊将力引导至提肌 和会阴来模拟人类的情况我们掌握的信息 得到了强烈支持，我们认为， 老鼠的行为与人类相似。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）， 衰老影响几种生长因子的基因和蛋白表达 (IGF系统，FGF，NGF，TGF，PDGF）和受体（肾上腺素能，毒蕈碱 和雌激素），这反过来又改变了组织的结构和功能。 机械装置。将通过填写 具体目标如下： 1.研究并比较了两种组织的功能、超微结构、细胞形态和 分子的变化，a）。在怀孕期间和 自发分娩后，B）催产素诱导分娩后和c） 在剖腹产分娩后。 2.检查功能，超微结构，细胞和分子 反复产伤后胎心机制的变化。 3.检查功能，超微结构，细胞和分子 模拟产伤后胎心机制的变化， 双侧卵巢切除术 4.确定功能、超微结构、细胞和分子 联合模拟分娩后胎心机制的变化 创伤卵巢切除术和衰老

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.