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，因为它们与部分性小肠梗阻有关。将阻塞豚鼠与年龄和性别匹配的正常豚鼠进行比较，以分析传入神经信号转导（特定目标3）的可能差异及其与阻塞期间几何（特定目标1）和生物力学重塑（特定目标2）的关系。我们的目标是获得详细的形态和机械数据，包括肌肉收缩特性的正常和阻塞的豚鼠小肠，并将它们与肠梗阻引起的组织重塑。因此，需要使用和进一步发展新的扩张方案、新的理论和方法。上述数据与传入神经信号一起将用于表征机械感受器反应的刺激反应功能。主要假设是部分肠梗阻将导致机械感觉特性的变化，并且可以在几何和生物力学重构与传入神经信号转导的变化之间建立数学关系。虽然以前的研究表明，形态和生物力学重塑，包括肌肉细胞肥大，增加刚度的肠壁和改变运动，从生物工程的角度来看，还有很多有待确定。研究将集中在零应力状态下小肠壁的多维应力-应变特性的确定，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）和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，为了处理肠梗阻的复杂性，需要一个生物工程模型。一个主要目标是证明通过使用多学科方法可以大大增强对GI疾病的理解，所述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、生物学以及医学科学和诊断学。

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.