平滑肌性质和排列改变对气道壁应力分布影响的数值模拟研究

气道平滑肌肥大、增生、力学性质和排列方向改变发生于许多慢性呼吸系统疾病中,引起气道内应力环境发生变化,成为导致气道狭窄的重要原因之一。本研究基于人体气道解剖结构,构建带有螺旋平滑肌层结构的气道三维有限元模型,并采用数值模拟的方法来研究平滑肌性质和排布变化对于气道在收缩过程中力学行为的影响。结果表明,气道内壁和平滑肌层在气道收缩过程中承受较大的应力;病理条件下平滑肌细胞数量和质量增加都将直接导致平滑肌层受力增大;平滑肌刚度的增加同样会引起该层组织承受更大应力;而在同等条件下,平滑肌细胞排列角度增加则会降低平滑肌层的应力值。     

气道平滑肌生物力学与哮喘病理机制的研究进展

哮喘病是危害人类健康的重要呼吸疾病,但其病理机制至今依然不完全清楚。由于呼吸依赖于各级肺组织在外力作用下的一系列力学过程,其力学因素必定在呼吸功能方面发挥着重要作用。其中,气道平滑肌细胞对物理环境很敏感,异常的力学因素刺激将可能改变气道平滑肌细胞的结构和／或功能,导致气道平滑肌过度收缩等病理变化。近年来,人们对气道平滑肌生物力学及其在哮喘的病理机制中的作用展开了大量研究,获得了许多重要的发现。本文将围绕气道平滑肌与肺中的力学环境介绍有关研究的最新进展,包括气道平滑肌收缩和骨架纤维的组织结构,气道平滑肌功能长度范围以及适应性,力学刺激引起的气道平滑肌细胞结构和功能的变化,气道平滑肌紧张度对应变诱导的响应的调控,细胞骨架软玻态动力学行为等,并探讨气道平滑肌生物力学与哮喘病病理机制的关系。     

镍钛合金网状气道支架置入术的计算机数值模拟分析

气道狭窄已成为一种较为常见的呼吸系统疾病,临床上往往需要进行气道支架置入术以实现气道的快速扩张,缓解患者的呼吸困难。但支架置入后常会出现肉芽组织过度增生的现象,严重的会造成气道的再狭窄。基于"应力-生长"关系的理论,肉芽组织的过度增生可能与局部力学环境的改变相关,特别是支架对气道壁的应力刺激。为此,研究将针对镍钛合金网状气道支架置入术展开计算机数值模拟,以分析支架置入前后局部力学环境的改变。结果显示气道支架置入后,狭窄处壁面的局部应力环境发生了显著的改变,其壁面的扩张应力明显升高且应力集中的现象较为严重。我们认为显著改变的局部应力环境可能是造成气道肉芽组织过度增生的因素之一。     

基于逆向工程的人体气道重建及其流场分析

目的 针对老年人气管萎缩导致整体气道尺寸变小的情况，研究狭窄气道重建及不同呼吸状态下空气流场对气道的影响。方法 运用Mimics建立人体气道的三维模型，利用计算流体动力学方法对气道内的流场进行仿真，分析并比较不同呼吸状态下气管内壁压强及其气流的分布状态。结果 在不同呼吸状态下，气管内壁压强数值在主气管内壁相对均匀，但在支气管狭窄段的气流入口处出现明显下降，在最狭窄的区域附近达到负压。气流速度从气管管道中心向边界层递减，流速在狭窄处达到最大值。气流穿过狭窄区域后产生涡流，且入口流速越大，正压和负压压强越大，狭窄处压降越明显，涡流现象越明显。结论 气道狭窄区域因负压造成继续收缩，会导致病人呼吸困难，而涡流会使气管壁受到气动剪切应力的影响可能损伤气道壁黏膜。因此，了解萎缩狭窄气道内的压强分布及流速分布情况，可为此类病变气道的临床诊治提供参考依据。     

哮喘等慢性气道疾病中气道缩窄的生物力学模型研究最新进展

虽然对于探索哮喘等气道疾病的潜在治疗方法和揭示气道系统中有趣的生物物理现象等意义重大,气道缩窄的生物力学模型研究一直是既吸引人又充满挑战的研究领域。近年来,这方面的研究呈现方兴未艾的形势,新的现象和新的研究思路不断出现。本文简要介绍这方面部分最新的研究进展,重点介绍针对哮喘气道缩窄行为,致力于解释在体气道行为的生物力学模型,尤其是不仅探讨孤立气道力学行为,而且也探讨气道间相互耦合和与周围环境耦合的气道力学模型。这些相互作用涉及气道和缠绕其上的气道平滑肌层,也涉及气道动态相互作用导致的气道—肺实质通气的空间分布形态等新颖的行为和现象。     

端部形状对支架-食管耦合系统力学行为的影响

目的研究食管支架不同端部形状对支架-食管系统力学行为的影响。方法通过有限元仿真,对不同端部形状(直筒形、杯球形和双喇叭形)的编织型食管支架及其与食管腔道构成耦合系统之间力学行为进行分析,并比较3种不同端部形状的裸支架和覆膜支架对食管内壁应力分布和食管狭窄区扩张的影响。结果裸支架使食管狭窄率降低的程度比覆膜支架高,并且裸支架使食管的等效应力和食管内壁的接触应力都远大于覆膜支架植入后的情况;支架不同的端部形状对食管健康区域内的等效应力和接触应力有很大影响,在食管与杯球形支架的杯端中部和双喇叭形支架端部边缘所接触的区域内出现应力集中;3种不同端部的编织型食管支架都具有良好贴壁性能。结论不同的支架端部形状使食管内壁产生不同应力状态。应力越大,食管组织增生的可能性越大,但支架移位的可能性越小。了解支架端部形状对支架性能的影响,可为支架的优化设计和临床选型提供重要的理论依据。     

角膜胶原交联后应力重分布的有限元研究

目的利用有限元的方法,探索角膜胶原交联手术后基质层中应力再分布的规律。方法通过提取正常兔眼角膜OCT图像的轮廓,建立轴对称的分区分层几何模型,赋予几何模型不同分布规律的弹性模量,探究交联后局部力学性质改变对于应力在角膜中再分布规律的影响。结果交联导致的力学性质的改变对于角膜基质层中应力的分布有显著影响,交联模型中央交联区域及交界区域前基质层的应力显著上升,比非交联模型提高20%～40%,后基质层的应力明显下降,比非交联模型降低10%～15%。结论交联术后角膜中央区域力学性质增强会改变基质层内应力分布的规律,使得原有应力沿角膜深度方向和沿角膜中央向边缘方向近似线性递增的规律消失,应力在深度方向的分布更加均匀。     

血管残余应力的两种求解方法及其应用

目的求解血管残余应力,为采用有限元方法研究血管应力的变化提供生物力学基础。方法采用弹性力学半逆解法得到血管的残余应力分布,与通过有限元软件ABAQUS模拟得到血管残余应力的分布进行对比,并在此基础上考虑支架置入的作用,比较残余应力对血管在体应力状态的影响。结果采用这两种方法得到的血管的3个正应力分量应力分布较为一致。残余应力的存在使血管的应力分布发生了变化,血管的最大应力由血管内壁转移到外壁处。结论在假定血管材料均质和各向同性的情况下,经典弹性力学半逆解法与有限元方法得到的残余应力结果有着较好的一致性;考虑残余应力的血管在体的应力分布与不考虑血管残余应力时有较大差异,血管内壁处应力降低明显。考虑血管的残余应力有助于更好地了解置入支架后血管真实的应力状态,从而为支架的优化设计提供参考。     

1,25-二羟维生素D3对哮喘小鼠气道重塑及基质金属蛋白酶-9表达的影响

目的:观察1,25-二羟维生素D3(VD)对哮喘小鼠气道重塑及其肺组织中基质金属蛋白酶-9(MMP-9)表达的影响,探讨VD在哮喘治疗中的作用.方法:BALB/c小鼠随机分为对照组、哮喘组及VD组.卵蛋白致敏和激发建立慢性哮喘小鼠模型;HE染色观察各组气道结构改变情况;采用计算机图像分析系统评价各组气道重塑情况;采用RT-PCR法检测各组的MMP-9mRNA表达水平.结果:①HE染色提示哮喘组与对照组相比出现炎性细胞浸润增多、上皮细胞脱落及平滑肌细胞层增厚等气道重塑改变,而VD组可部分逆转上述病理改变;②VD组的支气管内壁厚度、平滑肌层厚度和平滑肌细胞核数显著低于哮喘组,但仍高于对照组(P<0.05);③VD组肺组织MMP-9mRNA表达水平均明显低于哮喘组,但仍高于对照组(P<0.05).结论:VD干预可明显减轻慢性哮喘气道重塑的病理改变;并可通过部分抑制肺内MMP-9的表达来延缓气道重塑进程.     

Ⅰ型胶原与异丙肾上腺素调控三维培养胶上大鼠气道平滑肌细胞的分枝结构形成

细胞形态学发生与个体发育和组织生物工程相关。本研究初步探索了气道平滑肌细胞在三维matrigel胶上的形态发生,证实三维胶底培养条件和Ⅰ型胶原是细胞群体自发生成分枝结构的必要微环境。临床缓解哮喘症状的气道舒张药物异丙肾上腺素有效抑制了该分枝形态发生,初步提示其需要生物力学因素的参与,同时该实验模型也可能具有检测临床气道舒张药物效果的功能。考虑到气道平滑肌具有收缩和舒张的特性,而在哮喘气道高反应现象中,平滑肌保持收缩状态,导致支气管通气受阻,因此,本研究也为进一步研究气道平滑肌细胞的力学特性提供了一个简便的模型。     

A biomechanical model of agonist-initiated contraction in the asthmatic airway

This paper presents a modelling framework in which the local stress environment of airway smooth muscle (ASM) cells may be predicted and cellular responses to local stress may be investigated. We consider an elastic axisymmetric model of a layer of connective tissue and circumferential ASM fibres embedded in parenchymal tissue and model the active contractile force generated by ASM via a stress acting along the fibres. A constitutive law is proposed that accounts for active and passive material properties as well as the proportion of muscle to connective tissue. The model predicts significantly different contractile responses depending on the proportion of muscle to connective tissue in the remodelled airway. We find that radial and hoop-stress distributions in remodelled muscle layers are highly heterogenous with distinct regions of compression and tension. Such patterns of stress are likely to have important implications, from a mechano-transduction perspective, on contractility, short-term cytoskeletal adaptation and long-term airway remodelling in asthma.     

Cytoskeletal remodeling of the airway smooth muscle cell: a mechanism for adaptation to mechanical forces in the lung

Airway smooth muscle is continuously subjected to mechanical forces caused by changes in lung volume during breathing. These mechanical oscillations have profound effects on airway smooth muscle contractility both in vivo and in vitro. Alterations in airway smooth muscle properties in response to mechanical forces may result from adaptive changes in the organization of the actin cytoskeleton. Recent advances suggest that in airway smooth muscle, two cytosolic signaling proteins that associate with focal adhesion complexes, focal adhesion kinase (FAK) and paxillin, are involved in transducing external mechanical signals. FAK and paxillin regulate changes in the organization of the actin cytoskeleton and the activation of contractile proteins. Actin is in a dynamic state in airway smooth muscle and undergoes polymerization and depolymerization during the contraction-relaxation cycle. The organization of the cytoskeletal proteins, vinculin, talin, and alpha-actinin, which mediate linkages between actin filaments and transmembrane integrins, is also regulated by contractile stimulation in airway smooth muscle. The fluidity of the cytoskeletal structure of the airway smooth muscle cell may be fundamental to its ability to adapt and respond to the mechanical forces imposed on it in the lung during breathing.     

转化生长因子-β在哮喘气道炎症与重塑中的作用

Transforming growth factor-β(TGF-β) was reported to be increased in asthma in some studies. Accumulation of TGF-β in airway promotes smooth muscle cell mitogenesis and hyperplasia, and in-duces fibroblast and myofibroblast and smooth muscle proliferation as well as increase in protein synthesis in connective tissue(such as collagen deposition on the reticular basement membrane). The autocrine induction of collagen expression by smooth muscle may contribute to the thickening of the reticular basement membrane, irre-versible f‘throsis and remodeling seen in the airways in some asthmatics. TGF-β is considered to be a major fi-brogenic cytokine. It can increase smooth muscle mass and lead to severe bronchial obstruction in an asthma at-tack.     

豚鼠哮喘模型气道重建对气道反应性的影响

目的:通过小剂量致敏原反复致敏建立豚鼠慢性哮喘模型,设定不同时点(4、6、8周)观察气道结构及气道反应性的变化,探讨气道重建对气道反应性的影响。方法:采用低剂量卵白蛋白反复致敏、激发豚鼠,制作哮喘动物模型,应用氯化乙酰胆碱静脉注射进行支气管激发实验,进行支气管肺泡灌洗并计数灌洗液的白细胞总数及分类。应用图像分析系统对豚鼠气道进行形态学测量。结果:哮喘8周组以纤维组织增生及平滑肌厚度增加最为显著。气道高反应性以哮喘4周组增高最明显,而随着与致敏原接触时间的延长,气道高反应性逐渐降低,到哮喘8周组与正常对照组相比已无显著差异。结论:长时间卵白蛋白吸入致敏可以引起哮喘豚鼠气道反应性的变化,这种变化与气道重建的发生相关联。     

A Micromechanical Model of Airway-Parenchymal Interdependence

The forces of parenchymal interdependence in the lung are potent inhibitors of airway smooth muscle shortening, as evidenced by the marked dependence of bronchial responsiveness on lung volume. In this study we developed a mathematical-computer model of the effects of parenchymal interdependence on airway smooth muscle shortening. A three-dimensional network of cuboidal alveolar walls was tethered at its boundaries and surrounded a single airway with mechanical properties identical to the alveolar parenchyma. The walls were assigned highly nonlinear properties so that the pressure-volume behavior of the model matched that measured in dogs. Constriction of the airway was achieved by increasing the circumferential tension in the airway wall, and then solving the force-balance equations of the model to calculate the equilibrium configurations of the airway wall and all the interconnecting alveolar walls. The changes in airway resistance predicted by the model at various transpulmonary pressures (P _tp were compared to those obtained by the alveolar capsule oscillator technique in dogs during induced bronchoconstriction at various P _tp (Balassy et al., J. Appl. Physiol. 78:875–880, 1995). The model matched the data reasonably well at P _tp values above about 0.5 kPa, but was too responsive at lower P _tp We were able to make the model match the data at all P _tpby including an additional stiffness term, such as might conceivably arise from the airway wall itself. ©     

Cytoskeletal mechanics in airway smooth muscle cells

Mechanical properties and contractility of airway smooth muscle tissue are largely responsible for airway narrowing and airway hyperresponsiveness in asthma. To explain these pathological phenomena, investigators have studied the mechanical behaviour of airway smooth muscle cells and its relationship to the underlying cellular biophysical and biochemical mechanisms. During the past decade, a growing body of evidence has indicated that a deformable intracellular polymer network, known as the cytoskeleton, plays a major role in transmitting and distributing mechanical forces within the cell and in their conversion into biochemical responses. We review here evidence suggesting that the tensed and crosslinked cytoskeletal lattice, the contractile apparatus, and the cytoskeleton–extracellular matrix interactions are key determinants of mechanical properties and mechanosensing of airway smooth muscle cells, with the mechanical distending stress of the cytoskeleton playing the central role.     

氟伐他汀对哮喘气道重塑的抑制作用及机制研究

目的:探讨氟伐他汀对哮喘气道重塑过程的影响及分子机制。方法:以卵蛋白致敏的豚鼠哮喘模型为对象,观察正常对照组、哮喘组及氟伐他汀+哮喘组之间气道平滑肌肌层厚度的差异。氟伐他汀+哮喘组即每次激发哮喘前30min吸入浓度为05g/L的氟伐他汀2mL。同时采用Dot-blot分子杂交法、免疫组化SABC法检测各组气道ras基因的mRNA和蛋白水平变化。结果:哮喘组气道平滑肌层平均厚度为(7427±330)μm,显著高于正常对照组(3857±337)μm(P<001);氟伐他汀+哮喘组的平滑肌层厚度为(5170±413)μm,明显低于哮喘组(P<005)。哮喘组平滑肌细胞的ras基因表达水平明显高于正常对照组,但氟伐他汀+哮喘组未出现该基因的高表达。结论:氟伐他汀在一定程度上能抑制哮喘气道重塑的病理过程,其发挥效应的机制之一是阻断平滑肌细胞rasp21信号转导途径。     

组胺受体拮抗剂可防治哮喘豚鼠气道重塑和酸碱平衡紊乱

目的:探讨组胺受体拮抗剂对哮喘豚鼠气道重塑和酸碱平衡紊乱的防治作用。方法:将豚鼠分为正常对照组、哮喘模型组、哮喘模型延续组、组胺组、组胺受体拮抗剂组。用高效液相色谱法检测血清组胺浓度；生化分析仪测血清Na+、Cl-浓度；血气分析仪测血pH、PaO2、PaCO2、AB、SB；图像分析系统测定气道黏膜层、平滑肌层厚度。结果:（1）哮喘模型组血清组胺浓度、气道壁黏膜层和平滑肌层厚度均明显高于正常对照组 （P<0.01）；哮喘模型延续组明显高于哮喘模型组（P<0.01）；组胺组明显高于哮喘模型延续组（P<0.01）；而组胺受体拮抗剂组低于哮喘模型延续组（P<0.05，P<0.01）；（2）哮喘模型组的PaO2低于正常对照组（P<0.01）；哮喘模型延续组的PaO2、pH、AB、SB低于、PaCO2高于哮喘模型组（P<0.01）；组胺组PaO2、pH、AB、SB低于、PaCO2高于哮喘模型延续组（P<0.01）；而组胺受体拮抗剂组PaO2、pH、AB、SB高于哮喘模型延续组（P<0.01），PaCO2则低于哮喘模型延续组（P<0.01）。示豚鼠哮喘时存在气道重塑和血清组胺浓度升高以及代谢性酸中毒与呼吸性酸中毒，外源性组胺可加重这些变化，组胺受体拮抗剂可缓解之。结论:组胺在哮喘气道重塑中起介导作用，组胺受体拮抗剂对防治哮喘气道重塑及酸碱平衡紊乱有一定作用。     

Some properties of the smooth muscle of rabbit portal vein

1. The morphology of the smooth muscle of the rabbit portal vein and its innervation were studied with fluorescence and electron microscopy. Two layers of smooth muscle were observed in the tunica media: an inner layer of circularly arranged muscle cells and an outer layer consisting of bundles of smooth muscle cells arranged in a near longitudinal direction. The membranes of neighbouring smooth muscle cells were occasionally fused to form ;tight junctions'.2. Bundles of non-myelinated nerve fibres were observed in the adventitia, and between bundles and layers of smooth muscle cells in the media. Studies on longitudinal sections with fluorescence microscopy revealed a network of varicose noradrenergic axons.3. Electrical and mechanical activity was recorded from longitudinal strips of smooth muscle from the media of the vein with a sucrose-gap apparatus.4. The preparation was spontaneously active under minimal resting tension (less than 150 mg) and at temperatures above 28 degrees C. Slow depolarizations led to a burst of spikes (multi-spike complexes), which corresponded to rhythmic contractions. In 10% of preparations, the interval between multi-spike complexes showed a slower depolarization, suggesting the record was from a pace-maker region.5. The frequency of spontaneous activity (3-27 beats/min) was very sensitive to changes in temperature and tension.6. Noradrenaline in low doses (0.01 mug) caused an increase in frequency of the multi-spike complexes. Higher doses (0.1-0.3 mug) initiated continuous high-frequency spiking, while very high doses (0.6-2.0 mug) caused maintained depolarization.7. Responses to repetitive electrical stimulation of the vein were qualitatively similar to those in response to exogenous noradrenaline. The relation between the mechanical response and the various parameters of stimulation was consistent with the stimulation of sympathetic nerve fibres in the wall of the vein.8. The actions of isoprenaline, phentolamine and propranolol indicated the presence of alpha ;excitatory' and beta ;inhibitory' adrenotrophic receptors on the smooth muscle.