Mechanosensory properties in the partially obstructed guinea pig small intestine

描述(由申请人提供)：本提案的总体目标是了解与部分小肠梗阻相关的小肠的生物力学和机械感觉特性。将豚鼠与年龄和性别匹配的正常豚鼠进行比较，以分析在传入神经信号转导(特异性目标3)方面的可能差异，以及它与梗阻过程中的几何(特异性目标1)和生物力学重构(特异性目标2)的关系。目的是获得详细的形态计量学和力学数据，包括正常和梗阻豚鼠小肠的肌肉收缩特性，并将其与肠梗阻引起的组织重塑联系起来。因此，需要使用和进一步发展新的膨胀方案、新的理论和方法。上述数据将与传入神经信号一起用于表征机械感受器反应的刺激-反应功能。主要的假设是部分肠梗阻会导致机械感觉特性的改变，几何和生物力学重塑与传入神经信号转导的变化之间可以建立数学关系。尽管先前的研究已经显示了包括肌细胞肥大、肠壁僵硬和运动改变在内的形态和生物力学重建，但从生物工程学的角度来看，仍有许多问题有待确定。这些研究将集中于在零应力状态下确定小肠壁的多维应力-应变特性，以及被动力学特性、肌肉收缩特性和传入神经信号的整合。这些研究将阐明机械刺激(应力和应变)与传入神经反应之间的关系，即将获得关于机械感受器行为的信息。其基本原理是，需要一种生物工程模型来处理复杂的肠梗阻。一个主要目标是证明，通过使用包括材料和数学科学、成像分析、细胞和组织生物工程、生物学以及医学和诊断学在内的多学科方法，可以极大地提高对G1疾病的理解。

DESCRIPTION (provided by applicant): The general objective of this proposal is to understand the biomechanical and mechanosensory properties of the small intestine as they relate to partial small intestinal obstruction. Guinea pigs with obstruction will be compared to age- and sex-matched normal guinea pigs to analyze possible differences in afferent nerve signal transduction (Specific Aim 3) and how it relates to the geometric (Specific Aim 1) and biomechanical remodeling (Specific Aim 2) during obstruction. The goals are to obtain detailed morphometric and mechanical data including muscle contraction characteristics on the normal and obstructed guinea-pig small intestine and to relate them to the tissue remodeling elicited by the intestinal obstruction. Hence, new distention protocols, new theory and methods need to be used and further developed. The abovementioned data together with afferent nerve signals will be used to characterize the stimulus-response function for mechanoreceptor responses. The main hypothesis is that partial intestinal obstruction will lead to changes in the mechanosensory properties and that a mathematical relationship can be established between the geometric and biomechanical remodeling and the changes in afferent nerve signal transduction. Although previous studies have shown morphological and biomechanical remodeling including muscle cell hypertrophy, increased stiffness of the intestinal wall and altered motility, much remains to be determined from a bioengineering point of view. The studies will focus on determination of multidimensional stress-strain properties of the small intestinal wall with the zero-stress state taking into account, and on the integration of the passive mechanical properties, the muscle contractile properties, and afferent nerve signals. The studies will shed light on the relation between the mechanical stimulus (stress and strain) and the afferent nerve response, i.e. information on mechanoreceptor behavior will be obtained. The rationale is that a bioengineering model is needed in order to deal with the complexity of intestinal obstruction. A major goal is to demonstrate that the understanding of Gl diseases can be greatly enhanced by using a multidisciplinary approach including material and mathematical sciences, imaging analysis, cell and tissue bioengineering, biology, and medical science and diagnostics.