MICROVASCULAR PERMEABILITY OF NORMAL AND NEOPLASTIC TISSUES
MICROVASCULAR PERMEABILITY OF NORMAL AND NEOPLASTIC TISSUES
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DOI：
10.1016/0026-2862(86)90018-x
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发表时间：
1986-05-01
影响因子：
3.1
通讯作者：
JAIN, RK
中科院分区：
文献类型：
--
作者：
GERLOWSKI, LE;JAIN, RK
一种新的、无创的方法用于测量兔耳腔中生长的非恶性（成熟肉芽）和肿瘤（VX2癌）组织的微血管通透性。采用150000分子量的葡聚糖作为代表性示踪分子，用异硫氰酸荧光素（FITC）标记。采用耳室微血管等离子体层光度法测定体内血浆葡聚糖浓度。正常和肿瘤制剂的血药浓度均迅速上升至稳定状态，时间常数为4.06 +-。0.2秒，并在接下来的2小时内保持相对恒定的水平(消除时间常数= 1.77 .+-。0.9的同学们。105秒)。用同样的光度法测量了大分子从单个微血管外渗到血管外空间的情况。通过对外渗数据拟合一维渗透-扩散模型，确定了间质扩散系数和微血管渗透系数。右旋糖酐在肿瘤间质中的扩散率为2.2 +-。1.4的同学们。10-8 cm2/sec (n = 6)，肉芽组织间质为6.7 +-。4.4的同学们。10-10 cm2/sec （n = 6）。肿瘤微血管通透性为7.26 +-。3.29的同学们。10-8 cm/sec (n = 11)，肉芽组织57.24。39.24的同学们。10-8 cm/sec （n = 10）。肿瘤通透性增加（8倍，P < 0.002）和弥散性增加（33倍，P < 0.001）的结果为大分子量药物在实体瘤检测和治疗中的应用提供了合理依据。
A novel, noninvasive method was developed for microvascular permeability measurements in non-malignant (mature granulation) and neoplastic (VX2 carcinoma) tissues grown in the rabbit ear chamber. Dextran of 150,000 molecular weight, tagged with fluorescein isothiocyanate (FITC), was used as a representative tracer molecule. In vivo plasma concentration of dextran was measured by photometric analysis of the plasma layer of microvessels in the ear chamber. The plasma concentration in both normal and tumor preparations rose rapidly to a steady state with a time constant of 4.06 .+-. 0.2 sec, and remained relatively constant at that level for the next 2 hr (elimination time constant = 1.77 .+-. 0.9 .times. 105 sec). Extravasation of macromolecules from individual microvessels into the extravascular space was measured with the same photometric technique. Interstitial diffusion coefficients and microvascular permeability coefficients were determined by fitting a one-dimensional permeability-diffusion model to the extravasation data. The diffusivity of dextran in tumor interstitium was 2.2 .+-. 1.4 .times. 10-8 cm2/sec (n = 6) and in granulation tissue interstitium was 6.7 .+-. 4.4 .times. 10-10 cm2/sec (n = 6). Microvascular permeability in tumours was 7.26 .+-. 3.29 .times. 10-8 cm/sec (n = 11) and in granulation tissue was 57.24 .+-. 39.24 .times. 10-8 cm/sec (n = 10). These results on increased permeability (8-fold; P < 0.002) and increased diffusivity (33-fold; P < 0.001) in tumors provide a rational basis for the use of large-molecular-weight agents in the detection and treatment of solid tumors.