A Model of Strain-Dependent Glomerular Basement Membrane Maintenance and Its Potential Ramifications in Health and Disease
A Model of Strain-Dependent Glomerular Basement Membrane Maintenance and Its Potential Ramifications in Health and Disease
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DOI：
10.1115/1.4007098
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发表时间：
2012-08-01
影响因子：
1.7
通讯作者：
Segal, Yoav
中科院分区：
文献类型：
--
作者：
Barocas, Victor H.;Dorfman, Kevin D.;Segal, Yoav
建立并分析了IV型胶原在肾小球基底膜(GBM)中的周转模型，GBM是肾小球毛细血管壁的主要结构元素。该模型在GBM的沉积和去除中都包含了应变相关性，导致了沉积和去除平衡的组织应变。根据拉普拉斯定律，基底膜增厚减少了单位跨毛细血管压降的组织应变，但增加了维持肾小球滤过所需的跨毛细血管压降。模型结果与在Alport综合征和薄基底膜病中观察到的基底膜改变相一致，模型预测的平衡状态下毛细血管半径和厚度之间的线性关系与已发表的不同哺乳动物的数据一致。此外，该模型还根据几何、性质和力学环境预测了GBM中的最小可实现应变；即，无限厚的GBM仍将经历有限应变。尽管模型假设对于极厚的基底膜是无效的，但最小可达到的应变在以局灶性基底膜增厚为特征的疾病中可能是显著的，例如Alport综合征。最后，对模型参数的合理取值的检验表明，肿胀压降--由于大分子导致的血浆和滤液之间的渗透压差--在设定GBM菌株中起着重要作用，因此，蛋白质渗入尿液可能对某些GBM损伤具有保护作用。[DOI：10.1115/1.4007098]
A model is developed and analyzed for type IV collagen turnover in the kidney glomerular basement membrane (GBM), which is the primary structural element in the glomerular capillary wall. The model incorporates strain dependence in both deposition and removal of the GBM, leading to an equilibrium tissue strain at which deposition and removal are balanced. The GBM thickening decreases tissue strain per unit of transcapillary pressure drop according to the law of Laplace, but increases the transcapillary pressure drop required to maintain glomerular filtration. The model results are in agreement with the observed GBM alterations in Alport syndrome and thin basement membrane disease, and the model-predicted linear relation between the inverse capillary radius and inverse capillary thickness at equilibrium is consistent with published data on different mammals. In addition, the model predicts a minimum achievable strain in the GBM based on the geometry, properties, and mechanical environment; that is, an infinitely thick GBM would still experience a finite strain. Although the model assumptions would be invalid for an extremely thick GBM, the minimum achievable strain could be significant in diseases, such as Alport syndrome, characterized by focal GBM thickening. Finally, an examination of reasonable values for the model parameters suggests that the oncotic pressure drop-the osmotic pressure difference between the plasma and the filtrate due to large molecules-plays an important role in setting the GBM strain and, thus, leakage of protein into the urine may be protective against some GBM damage. [DOI: 10.1115/1.4007098]