| Objective To study the protective effect and mechanism of different dosages 6% medium molecular hydroxyethyl starch (HES 200/0.5) on acute lung injury (ALI) in endotoxemia rats; to find the best dosage and to provide a theoretic basis for clinical application of HES to prevent ALI. Methods Fifty healthy sanitary male SD rats weighing 250~300g were randomly divided into 5 groups with 10 animals in each group. The animals were anesthetized with 3% pentobarbital 30mg·kg-1. Lipopolysaccharide (LPS) 5mg·kg-1 was injected to induce ALI through right femoral vein. In group A1-A3 1min after LPS IV, 6% HES 3.75ml·kg-1,7.5ml·kg-1,15ml·kg-1 were continuously intravenous infused through right internal jugular vein at a rate of 0.2ml·ml-1 respectively; group B received LPS and 0.9% NS 7.5ml·kg-1; Group C served as control one by 0.9% normal saline (NS) of the same volume. During the four hours, the mortality of each group was recorded. 1ml blood sample were taken from coeliaca artery to analyze PaO2, PaCO2 and BE value before giving out blood and executing them. Right upper lobe of lung was calculated lung water ratio (LWR). The left lobe of lung were lavaged with 0℃~4℃NS through the left main bronchus to obtain bronchoalveolar lavage fluid (BALF). The total protein content (TPC) of BALF, lung maleic dialdehyde (MDA), nitrice oxide (NO) contents and activity of superoxide dismutase (SOD) was measured by colorimetry. Numbers of white blood cell (WBC) and percent of poly morphonuclear neutrophil (PMN) in BALF were gained in each group. Macroscopical changes were also observed and microstructures were studied further with light and electronic microscope. Rusults Mortalities of group A1and A3 were significantly higher than those of other three groups. PaO2, BE values were significantly lower in group B than those in any other group(P < 0.01). PaCO2 were significantly lower in group A3 than those in group A2, B, and C. LWR, MDA, NO ,TPC, numbers of WBC and percent of PMN in BALF was increased significantly in group A1, A3 and B, however, the activity of lung SOD in group A1, A3, B was decreased significantly. But there was no difference in that of group A2 and C(P>0.05). Pathological damages of lung in group A1-A3 were severe less than that in group B. Especially 6% HES (200/0.5) 7.5 ml·kg-1 had the most significant effects to inhibited damages in acute lung injury. No remarkable damages were observed in group C. Conclusions 6% HES (200/0.5) has significantly protective effect of preventing and treating ALI induced by endotoxin. Different dosages 6% HES (200/0.5) can decrease the blood mucosity and prevent from forming tiny thrombus by diluting blood correspondingly; avoid the injury induced by ischemia/reperfusion (I/R). It also inhibits the activity of nuclear factor Kappa-B (NF-κB) and the activation of endotheliocyte. So it may decrease the expression of soluble adhesion molecule. It can significantly inhibit and prevent WBC from conglutinating and moving, accordingly jam the leak of capillary vessel and decrease the degree of acute lung injury induced by LPS. However, the protective effect of HES 7.5 ml·kg-1 was best .
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