Hydrodynamic regulation of lymphatic transport and the impact of aging.
Hydrodynamic regulation of lymphatic transport and the impact of aging.
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DOI：
10.1016/j.pathophys.2009.09.002
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发表时间：
2010-09
期刊：
影响因子：
--
通讯作者：
Zawieja DC
中科院分区：
文献类型：
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作者：
Gashev AA;Zawieja DC
为了完成其在体液调节/大分子稳态、免疫功能和脂质吸收中的正常作用;淋巴系统必须将淋巴液从间质空间运输到淋巴管中并通过淋巴管，通过淋巴结的淋巴隔室，回到淋巴结传出淋巴管中，并最终排空到大静脉中。通常的净压力梯度沿着这条路径通常不有利于淋巴的被动运动。因此，淋巴输送需要能量输入到淋巴中，以推动淋巴沿着这条路径移动。为此，淋巴系统使用一系列泵来产生淋巴流。因此，为了调节淋巴转运，必须控制淋巴泵和阻力。这篇综述着重于调节内源性淋巴泵的流体动力学因素，以及这些调节过程是如何随着年龄的增长而改变的。内在淋巴泵通过淋巴肌的快速/阶段性收缩产生，其由局部物理因素（压力/拉伸和流动/剪切）调节。增加的淋巴压力/拉伸通常会激活内在淋巴泵达到一个点，超过该点淋巴泵将开始失效。增加的淋巴液流动/剪切的效果在某种程度上更为复杂，因为它可以激活或抑制内在淋巴泵，这取决于流动的模式和幅度。在正常条件下，淋巴转运的流体动力学调节的模式和强度在淋巴树的各个部分中是不同的，这取决于局部流体动力学条件。此外，各种病理生理过程可影响淋巴转运。我们已经开始评估的影响，在大鼠胸导管淋巴运输特性的老化过程。压力/拉伸依赖性激活的内在泵显着受损，在老年大鼠胸导管（TD）和流量/剪切依赖性调节机制基本上是完全缺乏。淋巴运输的剪切依赖性调制的损失似乎与这些血管中正常eNOS表达的损失和iNOS表达的大幅上升有关。因此，淋巴转运系统的老化显著损害其转运淋巴的能力。我们认为这将改变正常的体液平衡，并对老年动物的免疫功能产生负面影响。需要进一步的研究来详细说明在正常和衰老条件下控制和改变淋巴转运的机制。
To accomplish its normal roles in body fluid regulation/macromolecular homeostasis, immune function, and lipid absorption; the lymphatic system must transport lymph from the interstitial spaces, into and through the lymphatics, through the lymphatic compartment of the nodes, back into the nodal efferent lymphatics and eventually empty into the great veins. The usual net pressure gradients along this path do not normally favor the passive movement of lymph. Thus, lymph transport requires the input of energy to the lymph to propel it along this path. To do this, the lymphatic system uses a series of pumps to generate lymph flow. Thus to regulate lymph transport, both lymphatic pumping and resistance must be controlled. This review focuses on the regulation of the intrinsic lymph pump by hydrodynamic factors and how these regulatory processes are altered with age. Intrinsic lymph pumping is generated via the rapid/phasic contractions of lymphatic muscle, which are modulated by local physical factors (pressure/stretch and flow/shear). Increased lymph pressure/stretch will generally activate the intrinsic lymph pump up to a point, beyond which the lymph pump will begin to fail. The effect of increased lymph flow/shear is somewhat more complex, in that it can either activate or inhibit the intrinsic lymph pump, depending on the pattern and magnitude of the flow. The pattern and strength of the hydrodynamic regulation of the lymph transport is different in various parts of the lymphatic tree under normal conditions, depending upon the local hydrodynamic conditions. In addition, various pathophysiological processes can affect lymph transport. We have begun to evaluate the influence of the aging process on lymphatic transport characteristics in the rat thoracic duct. The pressure/stretch-dependent activation of intrinsic pumping is significantly impaired in aged rat thoracic duct (TD) and the flow/shear-dependent regulatory mechanisms are essentially completely lacking. The loss of shear-dependent modulation of lymphatic transport appears to be related to a loss of normal eNOS expression and a large rise in iNOS expression in these vessels. Therefore, aging of the lymph transport system significantly impairs its ability to transport lymph. We believe this will alter normal fluid balance as well as negatively impact immune function in the aged animals. Further studies are needed to detail the mechanisms that control and alter lymphatic transport during normal and aged conditions.