The Effects of Hydroxyethyl Starch on Lung Capillary Permeability in Endotoxic Rats and Possible Mechanisms(九) -|官方,ag8879环亚手机|官网,环亚娱乐ag88|开户


The Effects of Hydroxyethyl Starch on Lung Capillary Permeability in Endotoxic Rats and Possible Mechanisms(九)

时间:2010-08-24 10:02:11??来源:??作者:

Another noteworthy phenomenon in our experiment is that the maximal effect of HES was observed at a dose of 7.5 mL/kg in most cases. This may be because most mediators are regulated by many factors. Besides NF-kB, C/EBP and AP-1 are both important in the expression of cytokines, chemokines, and adhesive molecules. Maybe HES has some reverse effects on these pathways or on other untested mediators, such as selectins, and ICAM. Thus the effects of larger doses may be partially offset by those reverse effects. Further experiments are needed to confirm, in vivo, these and other proinflammatory signaling pathways on which HES might exert an influence. Finally, our experiments suggest the best dose of HES for use in a clinical setting. Because 2.5 mL in rats represents approximately 10% of the blood volume, 7.5 mL/kg is comparable to a human subject weighing 70 kg receiving 500 mL of HES.

In summary, we have shown that HES (200/0.5) at doses of 3.75 and 7.5 mL/kg significantly reduced LPS-induced increases in lung capillary permeability. The proposed mechanism is that HES inhibits LPSinduced NF-kB activation, followed by inhibition of the lung CINC protein level, CD11b expression on the blood neutrophil cell surface, and lung neutrophil accumulation, thus reducing the LPS-induced increase in microvascular endothelial permeability in the lung.



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