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缓慢循环的Rho激酶依赖性肌动球蛋白横桥“滑动”解释了逼尿肌平滑肌固有的高顺应性。

Slowly cycling Rho kinase-dependent actomyosin cross-bridge "slippage" explains intrinsic high compliance of detrusor smooth muscle.

作者信息

Neal Christopher J, Lin Jia B, Hurley Tanner, Miner Amy S, Speich John E, Klausner Adam P, Ratz Paul H

机构信息

Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia; and.

Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia.

出版信息

Am J Physiol Renal Physiol. 2017 Jul 1;313(1):F126-F134. doi: 10.1152/ajprenal.00633.2016. Epub 2017 Mar 29.

Abstract

Biological soft tissues are viscoelastic because they display time-independent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared with the large increase produced when the viscosity was absent and only pseudoelasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca-containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, with the plasticity resulting from motor protein activation. This model explains the mechanism of intrinsic bladder compliance as "slipping" cross bridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin cross-bridge activity, and identifies a novel molecular target for compliance regulation, both physiologically and therapeutically.

摘要

生物软组织具有粘弹性,因为它们表现出与时间无关的伪弹性和与时间相关的粘性。然而,有证据表明膀胱也可能表现出可塑性,可塑性被定义为应变增加,这种应变是不可恢复的,除非肌肉做功。在本研究中,使用电子杠杆诱导应力和应变的可控变化,以确定兔逼尿肌平滑肌(rDSM)最好被描述为粘弹性还是粘弹性塑性。通过连续的斜坡加载和卸载循环,应力-应变和刚度-应力分析表明,rDSM表现出可逆的粘弹性,并且粘性成分负责在低应力下建立高刚度,与不存在粘性且仅伪弹性控制组织行为时应力增加导致的大幅增加相比,随着应力增加,该刚度仅适度增加。该研究还表明,rDSM经历了与塑性变形和蠕变相关的软化,当组织在含钙溶液中孵育时,这种软化会缓慢逆转。总之,数据支持将DSM作为一种粘弹性塑性材料的模型,其可塑性源于运动蛋白的激活。该模型解释了膀胱固有顺应性的机制为“滑动”横桥,预测壁张力不仅取决于囊泡压力和半径,还取决于肌动球蛋白横桥活性,并确定了一个在生理和治疗方面调节顺应性的新分子靶点。

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