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小肠的生物力学和机械感觉特性，因为它们与部分小肠梗阻有关。将梗阻豚鼠与年龄和性别匹配的正常豚鼠进行比较，分析梗阻期间传入神经信号转导（Specific Aim 3）可能存在的差异，以及它与几何（Specific Aim 1）和生物力学重构（Specific Aim 2）的关系。目的是获得正常和梗阻豚鼠小肠的详细形态学和力学数据，包括肌肉收缩特征，并将其与肠梗阻引起的组织重塑联系起来。因此，新的扩张方案、新的理论和方法需要应用和进一步发展。上述数据与传入神经信号将用于表征机械受体反应的刺激-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改变之间可以建立数学关系。虽然先前的研究表明形态学和生物力学重塑包括肌肉细胞肥大，肠壁硬度增加和运动性改变，但从生物工程的角度来看，还有很多有待确定的。研究将侧重于确定考虑零应力状态下小肠壁的多维应力-应变特性，以及对被动力学特性、肌肉收缩特性和传入神经信号的整合。这些研究将揭示机械刺激（应力和应变）与传入神经反应之间的关系，即获得机械感受器行为的信息。其基本原理是需要一个生物工程模型来处理肠梗阻的复杂性。主要目标是证明通过使用多学科方法，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、医学科学和诊断学，可以大大提高对Gl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.