Mathematical Model of Oxygen Transport in Tuberculosis Granulomas.
Mathematical Model of Oxygen Transport in Tuberculosis Granulomas.
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DOI：
10.1007/s10439-015-1415-3
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发表时间：
2016-04
影响因子：
3.8
通讯作者：
Jain RK
中科院分区：
文献类型：
--
作者：
Datta M;Via LE;Chen W;Baish JW;Xu L;Barry CE 3rd;Jain RK
肺肉芽肿是结核分枝杆菌（MTB）感染的标志，是致密的细胞病变，通常以缺氧和坏死区域为特征，部分原因是氧气运输受限。肉芽肿内低氧可损害宿主的免疫反应，而结核分枝杆菌能够适应低氧环境并持续存在。在这里，我们使用了一个基于生理学的氧气扩散和消耗的数学模型来计算肉芽肿内的氧气分布，假设Michaelis-Menten动力学。一个近似的分析解决方案，使用先验和新估计的参数，从实验数据在兔模型的结核病，能够预测缺氧和坏死区域的大小与实验结果一致的动物模型。这种对转运限制的定量理解可以为未来的结核病治疗策略提供信息，这些策略可能包括辅助宿主导向疗法，这些疗法有助于氧气和药物的递送，从而获得更有效的治疗。
Pulmonary granulomas—the hallmark of Mycobacterium tuberculosis (MTB) infection—are dense cellular lesions that often feature regions of hypoxia and necrosis, partially due to limited transport of oxygen. Low oxygen in granulomas can impair the host immune response, while MTB are able to adapt and persist in hypoxic environments. Here, we used a physiologically based mathematical model of oxygen diffusion and consumption to calculate oxygen profiles within the granuloma, assuming Michaelis–Menten kinetics. An approximate analytical solution—using a priori and newly estimated parameters from experimental data in a rabbit model of tuberculosis—was able to predict the size of hypoxic and necrotic regions in agreement with experimental results from the animal model. Such quantitative understanding of transport limitations can inform future tuberculosis therapeutic strategies that may include adjunct host-directed therapies that facilitate oxygen and drug delivery for more effective treatment.