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羟乙基淀粉(HES 130/0.42 和 HES 200/0.5)对激活的肾小管上皮细胞的影响。

The effect of hydroxyethyl starches (HES 130/0.42 and HES 200/0.5) on activated renal tubular epithelial cells.

机构信息

Institute of Anesthesiology, University of Zurich, Zurich, Switzerland.

出版信息

Anesth Analg. 2010 Feb 1;110(2):531-40. doi: 10.1213/ANE.0b013e3181c03c97. Epub 2009 Nov 12.

Abstract

BACKGROUND

Acute renal failure is a frequent complication of sepsis. Hydroxyethyl starch (HES) is widely used in the treatment of such patients. However, the effect of HES on renal function during sepsis remains controversial. We established an in vitro model of tumor necrosis factor-alpha (TNF-alpha)-stimulated human proximal tubular epithelial (HK-2) cells to assess the possible effects of HES 130/0.42 and HES 200/0.5 on these activated cells.

METHODS

HK-2 cells were stimulated with TNF-alpha in the presence or absence of HES 130/0.42 or 200/0.5. After 4, 10, and 18 h of incubation, monocyte chemoattractant protein-1 (MCP-1), a key chemoattractant for neutrophils and macrophages, was measured. In addition, viability and cytotoxicity assays were performed.

RESULTS

MCP-1 expression was doubled upon TNF-alpha exposure. In the presence of 2% and 4% HES 200/0.5 in 98% (96%) medium over a stimulation time period of 10 h and 18 h, the MCP-1 concentration was decreased between 26% and 56% (P < 0.05). TNF-alpha stimulation resulted in a significant decrease of viability by 53%-63%, whereas viability decreased by only 32%-40% in coincubation with HES 130/0.42 (P < 0.005) and remained even less affected by TNF-alpha in the presence of HES 200/0.5 (P < 0.001). The TNF-alpha-induced cell death rate was attenuated in the presence of HES 200/0.5 (P < 0.05).

CONCLUSIONS

This in vitro study shows that both HES products modulate cell injury upon inflammatory stimulation. The effect was more pronounced in the HES 200/0.5 group than for HES 130/0.42, suggesting a possible biological difference between the HES types.

摘要

背景

急性肾衰竭是脓毒症的常见并发症。羟乙基淀粉(HES)被广泛用于此类患者的治疗。然而,HES 对脓毒症患者肾功能的影响仍存在争议。我们建立了肿瘤坏死因子-α(TNF-α)刺激的人近端肾小管上皮(HK-2)细胞的体外模型,以评估 HES 130/0.42 和 HES 200/0.5 对这些激活细胞的可能影响。

方法

在存在或不存在 HES 130/0.42 或 200/0.5 的情况下,用 TNF-α刺激 HK-2 细胞。孵育 4、10 和 18 小时后,测量单核细胞趋化蛋白-1(MCP-1),这是中性粒细胞和巨噬细胞的关键趋化因子。此外,还进行了细胞活力和细胞毒性测定。

结果

TNF-α 暴露使 MCP-1 表达增加一倍。在存在 2%和 4%的 HES 200/0.5 时,在 10 小时和 18 小时的刺激时间内,MCP-1 浓度降低了 26%-56%(P<0.05)。TNF-α 刺激导致细胞活力显著下降 53%-63%,而在与 HES 130/0.42 共孵育时,细胞活力仅下降 32%-40%(P<0.005),在存在 HES 200/0.5 时,细胞活力受 TNF-α的影响更小(P<0.001)。在存在 HES 200/0.5 的情况下,TNF-α 诱导的细胞死亡率降低(P<0.05)。

结论

这项体外研究表明,两种 HES 产品均能调节炎症刺激后的细胞损伤。在 HES 200/0.5 组中的效果更为明显,而在 HES 130/0.42 组中的效果不明显,表明两种 HES 类型之间可能存在生物学差异。

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