肿瘤细胞靶器官特异性捕获和黏附行为的研究进展

肿瘤转移是恶性肿瘤的主要生物学特征,是引起癌症患者死亡的重要原因。肿瘤转移的发生是一个复杂的动态过程,涉及到血管、淋巴道和转移器官微环境等诸多因素调控。在其血管途径的转移过程中,微血管内肿瘤细胞的靶器官特异性捕获和黏附是肿瘤在特定器官内转移形成的关键性步骤。为更好地了解和认识肿瘤细胞捕获和黏附行为及肿瘤转移形成的机制,本文就微血管内肿瘤细胞捕获和黏附研究中的理论假说、研究方法及其生物力学、内皮细胞和趋化因子等调控因素的研究进展进行了简要的综述,并归纳了该领域内若干可供探索的途径和新方向。     

Three-Dimensional Computational Fluid Dynamics Modeling of Alterations in Coronary Wall Shear Stress Produced by Stent Implantation

Rates of coronary restenosis after stent implantation vary with stent design. Recent evidence suggests that alterations in wall shear stress associated with different stent types and changes in local vessel geometry after implantation may account for this disparity. We tested the hypothesis that wall shear stress is altered in a three-dimensional computational fluid dynamics (CFD) model after coronary implantation of a 16 mm slotted-tube stent during simulations of resting blood flow and maximal vasodilation. Canine left anterior descending coronary artery blood flow velocity and interior diameter were used to construct CFD models and evaluate wall shear stress proximal and distal to and within the stented region. Channeling of adjacent blood layers due to stent geometry had a profound affect on wall shear stress. Stagnation zones were localized around stent struts. Minimum wall shear stress decreased by 77% in stented compared to unstented vessels. Regions of low wall shear stress were extended at the stent outlet and localized to regions where adjacent axial strut spacing was minimized and the circumferential distance between struts was greatest within the stent. The present results depict alterations in wall shear stress caused by a slotted-tube stent and support the hypothesis that stent geometry may be a risk factor for restenosis by affecting local wall shear stress distributions. © 2003 Biomedical Engineering Society. PAC2003: 8719Rr, 8710+e, 8780Rb, 8719Uv     

Effects of Periodic Body Acceleration on the <Emphasis Type="Italic">In Vivo</Emphasis> Vasoactive Response to N-<Emphasis Type="Italic">w</Emphasis>-nitro–L-arginine and the <Emphasis Type="Italic">In Vitro</Emphasis> Nitric Oxide Production

Periodic acceleration (pGz), a novel method of ventilatory support, is achieved using a platform that moves cyclically in the headward–footward direction. PGz has been shown to increase vascular shear stress and regional blood flows, as well as decrease pulmonary and systemic vascular resistances. PGz also increases nitric oxide (NO) production. This study was undertaken to determine the effects of pGz on the NO inhibiting effects of N-w-nitro–L-arginine (L-NAME) in vivo, and to determine if increased NO production due to pGz could be reproduced in vitro with isolated arteries. Pigs were assigned to conventional ventilation (CV), or pGz, with no additional breathing assistance. L-NAME was infused in cumulative doses of 1, 3, 10, 30, and 100 mg/kg. Cardiac output decreased in both groups by 50%. There was also a dose-dependent increase in blood pressure, pulmonary artery pressure, and vascular resistances. However, pGz attenuated the vascular response of L-NAME. Isolated porcine aortas exposed to nonpulsatile, pulsatile, and pulsatile flow plus pGz exhibited an increase in nitrites with the addition of pulsatile flow (300%, relative to steady flow), and a further increase with pGz (1000%, relative to steady flow). It has been determined that pGz, a novel method of increasing shear stress on the vascular endothelium, attenuates the vasoactive response to L-NAME. The in vitro experiments demonstrated that increases in NO production in vivo could be reproduced in vitro, which provides the opportunity to investigate the mechanisms of cardiovascular pGz effects. © 2003 Biomedical Engineering Society. PAC2003: 8719Uv, 8719Rr, 8780-y     

Hemodynamic modulation of monocytic cell adherence to vascular endothelium

Hemodynamic shear stress is hypothesized to contribute to the localization of atherosclerotic plaques to certain arterial sites. Monocyte recruitment to these sites is an early event in atherogenesis. To determine the possible mechanisms by which shear stress modulates monocyte adhesionin vivo, studies of human monocytic cell adherence to endothelium were conducted under different shear conditions in a parallel-plate flow chamber. The number of monocytes capable of developing firm adhesive contacts with endothelium decreased as shear stress-induced drag forces increased over the range of 0.5 to 30 dynes/cm². The number of adherent monocytic cells at a given shear stress was highly dependent on the activation state of the endothelium. To test the direct effect of shear stress on endothelial cell adhesivity, endothelial cells were presheared for 2 to 6 hr at 2, 10, or 30 dynes/cm², and monocytic cell adherence was quantified at 1 dyne/cm². Adherence increased 330% or 370% when endothelial cells were presheared for 2 hr at 2 or 10 dynes/cm², respectively, as compared to unsheared endothelium. In contrast, when endothelial cells were presheared at 30 dynes/cm², monocytic cell adherence at 1 dyne/cm² was not significantly different from unsheared controls. Increased monocytic cell adherence to presheared endothelium was via a vasuclar cell adhesion molecule 1 (VCAM-1)α₄β₁ mechanism, and enzyme-linked immunosorbent assay studies showed that preshearing at 2 dynes/cm² for 2 hr increased endothelial VCAM-1 expression by 38%. These data demonstrated that low levels of shear stress induce enthelial VCAM-1 expression and increase monocytic cell adherence via a VCAM-1/α₄β₁ mechanism. Thus, shear stress can modulate monocyte adherence to vascular endothelium through drag forces that affect the establishment and maintenance of adhesive bonds and by directly modulating the expression of endothelial VCAM-1. This dual effect of shear stress produces the most favorable conditions for adhesion at low-shear regions, where drag forces are low and induction of VCAM-1 is likely. The preferential adherence of monocytes to these regions may contribute to the localization of atherosclerotic plaques to low-shear regions of the arterial circulationin vivo.     

Strength training effects on physical performance and serum hormones in young soccer players

To determine the effects of simultaneous explosive strength and soccer training in young men, 8 experimental (S) and 11 control (C) players, aged 17.2 (0.6) years, were tested before and after an 11-week training period with respect to the load-vertical jumping curve [loads of 0–70 kg (counter-movement jump CMJ0–70)], 5- and 15-m sprint performances, submaximal running endurance and basal serum concentrations of testosterone, free testosterone and cortisol. In the S group, the 11-week training resulted in significant increases in the low-force portion of the load-vertical jumping curve (5–14% in CMJ0–30, P<0.01) and in resting serum total testosterone concentrations (7.5%, P<0.05), whereas no changes were observed in sprint running performance, blood lactate during submaximal running, resting serum cortisol and resting serum free testosterone concentrations. In the C group, no changes were observed during the experimental period. In the S group, the changes in CMJ0 correlated (P<0.05–0.01) with the changes in the 5-m (r=0.86) and 15-m (r=0.92) sprints, whereas the changes in CMJ40 correlated negatively with the changes in the testosterone:cortisol ratio (r=–0.84, –0.92, respectively, P<0.05). These data indicate that young trained soccer players with low initial strength levels can increase explosive strength by adding low-frequency, low-intensity explosive-type strength training. The inverse correlations observed between changes in CMJ40 and changes in the testosterone:cortisol ratio suggest that a transient drop in this ratio below 45% cannot always be interpreted as a sign of overstrain or neuroendocrine dysfunction.An erratum to this article can be found at     

低切应力对体外培养动脉形态学重建的影响

目的 研究低切应力对血管的生物学作用,探讨切应力与血管形态学重建的关系。方法 采用血管体外应力培养系统,培养猪颈总动脉,通过组织学、免疫组织化学和图像分析等方法,探讨低切应力作用下动脉重建的形态学改变。结果 切应力减小时,动脉发生显著的结构重建,其特征为管径缩小,壁面积减小,管壁增厚,壁厚／内径比增加;低切应力作用使动脉部分中膜VSMC由收缩型转变为合成型,表现为α-肌动蛋白含量下降,细胞核朝向改变,发生扭曲,变大变圆,核仁明显。结论 低切应力和血压改变所致的血管重建在形态学方面有很大不同,提示：切应力和血压改变对血管重建的作用机制不同;中膜VSMC的表型转换是低切应力引起血管重建的基础。     

剪切力对血管内皮细胞表达IL-8的影响

本文利用改进的流室装置, 通过精密蠕动泵提供剪切力, 选择5dyne/cm2、10dyne/cm2、15dyne/cm2三种剪切力, 施加于体外培养的血管内皮细胞, 作用不同时间, 用RIA的方法检测流体动力学对血管内皮细胞表达IL-8的影响.结果表示, 不同剪切力作用内皮细胞后, IL-8的表达量与剪切力大小及作用时间有关, 为时间依赖性增长, 在5dyne/cm2组和10dyne/cm2组中, IL-8表达量明显高于空白对照组, 而15dyne/cm2组与对照组相比有下降趋势, 提示高剪切力有可能抑制IL-8的分泌.通过观察不同大小剪切力对血管内皮细胞表达IL-8的影响, 为探讨剪切力对动脉粥样硬化的影响提供一些数据.     

结合RGD肽的聚酯材料表面粘附内皮细胞的抗剪切力研究

精氨酸-甘氨酸-天门冬氨酸(RGD)是许多粘附蛋白的高度保守氨基酸序列.生物材料表面结合RGD肽有助于内皮细胞在材料上的粘附、迁移和增殖.本研究在体外流动条件下观察结合RGD肽或纤维粘连蛋白的聚酯材料表面粘附内皮细胞的抗剪切能力,并通过观察肌动蛋白和踝蛋白的表达初步探讨影响细胞粘附稳定性的机制.结果显示材料表面结合RGD或纤维粘连蛋白可以增加细胞的粘附强度,提高抗剪切能力;而RGD和纤维粘连蛋白导致的细胞抗剪切能力增加可能与细胞内肌动蛋白和踝蛋白的表达增加有关.     

温度对单个人红细胞膜力学特性的即时作用

目的：探讨温度对单个红细胞膜力学性质的即时影响。 方法： 利用静态显微图像分析技术和动态显微图像分析技术，在无损、实时、在位的情况下，观察和测量不同温度下单个人红细胞的形态、大小、膜弯曲弹性模量和剪切弹性模量的变化。 结果： 红细胞的接触面积和直径随温度的升高而减小，胞膜的弯曲弹性模量和剪切弹性模量都在生理温度37 ℃时最小，而温度低于或高于37 ℃时红细胞膜的弯曲弹性模量和剪切弹性模量都增大。 结论： 红细胞在生理温度37 ℃时有最好的形态和力学变形性，便于发挥其生理功能。     

基于Zener模型的生物组织剪切模量测量

目的克服基于Voigt模型的超声振动检测方法的不足,使用Zener模型更加准确地测量生物组织剪切模量,为组织定征提供有效的手段。方法利用基于力学模型本构关系的剪切波传播速度公式,在获得剪切波在多个频率上速度的前提下,通过数学方法估计出介质的剪切模量。实验对象为不同浓度的凝胶模型和不同程度热力学损伤的猪肝脏,通过超声辐射力振动产生剪切波,获取剪切波在不同实验介质中的传播速度。结果分别用Voigt模型和Zener模型对速度值进行拟合,结果均显示Zener模型描述的准确性更高,并且所估计出的剪切模量能够很好地区分不同浓度的凝胶模型或不同损伤程度的猪肝。结论本方法为无创测量生物组织剪切模量提供了潜在的手段,对医学上的组织定征和疾病诊断有着重要的意义。