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金纳米粒子的大小和给药期对大鼠血浆流变学参数在较宽剪切率范围内的影响:体内。

The effects of size and period of administration of gold nanoparticles on rheological parameters of blood plasma of rats over a wide range of shear rates: in vivo.

机构信息

Physics and Astronomy, King Saud University, College of Science, Riyadh-11451, P.O. 2455, Saudi Arabia.

出版信息

Lipids Health Dis. 2011 Oct 27;10:191. doi: 10.1186/1476-511X-10-191.

DOI:10.1186/1476-511X-10-191
PMID:22032228
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3305902/
Abstract

BACKGROUND

Blood viscosity appears to be independent predictor of stroke, carotid intima-media thickening, atherosclerosis and most cardiovascular diseases. In an attempt to understand the toxicity and the potential threat of GNPs therapeutic and diagnostic use, an array of rheological parameters were performed to quantify the blood plasma response to different sizes and administration periods of GNPs over a wide range of shear rates.

METHODS

Healthy, thirty male Wistar-Kyoto rats, 8-12 weeks old (approximately 250 g body weight) were divided into control group (NG: n = 10), group 1 (G1A: intraperitoneal infusion of 10 nm GNPs for 3 days, n = 5 and G1B: intraperitoneal infusion of 10 nm GNPs for 7 days, n = 5), group 2 (G2A: intraperitoneal infusion of 50 nm GNPs for 3 days, n = 5 and G2B: intraperitoneal infusion of 50 nm GNPs for 7 days, n = 5). Dose of 100 μl of GNPs was administered to the animals via intraperitoneal injection. Blood samples of nearly 1 ml were obtained from each rat. Various rheological parameters such as torque, shear stress, shear rate, viscosity, plastic velocity, yield stress, consistency index (k) and flow index (n) were measured in the blood plasma of rats after the intraperitoneal administration of 10 and 50 nm GNP for 3 and 7 days using Brookfield LVDV-III Programmable rheometer.

RESULTS

The relationship between shear stress and shear rate for control, G1A, G1B, G2A and G2B was linearly related. The plastic viscosity and the yield stress values for G1A, G1B, G2A and G2B significantly (p < 0.05) decreased compared with the control. The n and k values calculated from equation (1). The k values for G1A, G1B and G2B decreased compared with the control; however the means were not significantly different. While G2A indicates no significant change compared with the control. The values of the flow behaviour index (n) were equal ≤ 1 for all the different GNPs sizes. The viscosity values measured for 10 and 50 nm GNPs (G1A, G1B, G2A and G2B) decreased compared with the control; however the means were not significantly different. The decrease in blood plasma viscosity values observed with all GNPs is particle size and administration period independent.

CONCLUSIONS

At these particular shear rates, the estimated rheological parameters are not influenced by GNPs size and shape, number of NPs, surface area and administration period of GNPs. This study demonstrates that the highly decrease in blood plasma viscosity was accompanied with the smaller 10 nm GNPs compared with the 50 nm GNPs. The decrease in blood plasma viscosity induced with 10 and 50 nm GNPs may be attributed to decrease in hematocrit and haemoglobin concentration in addition to erythrocyte deformability. This study suggests that histomorphologcal, histochemical and ultrastrucural investigations are needed to evaluate the inflammations and tissue injuries, in relation to the application of GNPs as a therapeutic and diagnostic tool.

摘要

背景

血液粘度似乎是中风、颈动脉内膜中层增厚、动脉粥样硬化和大多数心血管疾病的独立预测因子。为了了解 GNPs 治疗和诊断用途的毒性和潜在威胁,我们进行了一系列流变学参数研究,以在广泛的剪切率范围内量化不同大小和给药时间的 GNPs 对血浆的反应。

方法

将 30 只雄性 Wistar-Kyoto 大鼠(8-12 周龄,约 250g 体重)分为对照组(NG:n=10)、第 1 组(G1A:腹腔内输注 10nmGNPs3 天,n=5 和 G1B:腹腔内输注 10nmGNPs7 天,n=5)、第 2 组(G2A:腹腔内输注 50nmGNPs3 天,n=5 和 G2B:腹腔内输注 50nmGNPs7 天,n=5)。通过腹腔注射将 100μl 的 GNPs 剂量给予动物。从每只大鼠中获得近 1ml 的血液样本。使用 Brookfield LVDV-III 程控流变仪,在腹腔内给予 10nm 和 50nmGNP3 和 7 天后,测量大鼠血浆中的各种流变学参数,如扭矩、剪切应力、剪切率、粘度、塑性速度、屈服应力、稠度指数(k)和流动指数(n)。

结果

对照组、G1A、G1B、G2A 和 G2B 的剪切应力与剪切率之间呈线性关系。与对照组相比,G1A、G1B、G2A 和 G2B 的塑性粘度和屈服应力值显著(p<0.05)降低。根据方程(1)计算的 n 和 k 值。G1A、G1B 和 G2B 的 k 值与对照组相比有所降低;然而,平均值没有显著差异。而 G2A 与对照组相比没有显著变化。所有不同 GNPs 大小的流动行为指数(n)值均等于≤1。与对照组相比,测量的 10nm 和 50nmGNPs(G1A、G1B、G2A 和 G2B)的粘度值降低;然而,平均值没有显著差异。所有 GNPs 观察到的血浆粘度降低与颗粒大小和给药时间无关。

结论

在这些特定的剪切率下,估计的流变学参数不受 GNPs 大小和形状、纳米颗粒数量、表面积和 GNPs 给药时间的影响。本研究表明,与 50nmGNPs 相比,较小的 10nmGNPs 导致血浆粘度显著降低。与 10nm 和 50nmGNPs 诱导的血浆粘度降低可能归因于红细胞变形能力除了血细胞比容和血红蛋白浓度降低。本研究表明,需要进行组织形态学、组织化学和超微结构研究,以评估与 GNPs 作为治疗和诊断工具的应用相关的炎症和组织损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dac/3305902/b75ee406bf56/1476-511X-10-191-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dac/3305902/067ddc820e96/1476-511X-10-191-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dac/3305902/e6f2e7ed51cd/1476-511X-10-191-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dac/3305902/b75ee406bf56/1476-511X-10-191-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dac/3305902/067ddc820e96/1476-511X-10-191-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dac/3305902/e6f2e7ed51cd/1476-511X-10-191-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dac/3305902/b75ee406bf56/1476-511X-10-191-3.jpg

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