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Effect of Captopril on Lectin-Like Oxidized LDL Receptor-1 in Acute Lung Injury

Author: HanPengKai
Tutor: ZhangZuo
School: Chongqing Medical University
Course: Internal Medicine
Keywords: acute lung injury lipopolysaccharide captopril myeloper oxidase tumor necrosis factor-α lectin-like oxidized LDL receptor-1
CLC: R563.8
Type: Master's thesis
Year: 2011
Downloads: 12
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Abstract


PART ONE Protective effect of captopril on LPS-induced acute lung injuryObjective To study the change of myeloperoxidase （MPO） and tumor necrosis factor-α（TNF-α） in acute lung injury and the effect of captopril, and investigate the influence of captopril on inflammation in acute lung injury （ALI）.Methods Sprague-Dawley rats were randomly divided into 3 groups, a saline control group, a lipopolysaccharide （LPS） group （5mg/kg）, and a LPS+captopril group（1.25mg/kg）, each group 10 rats. Rats in LPS group were instilled intratracheally with 5 mg/kg LPS to induce acute lung injury, and rats in LPS+captopril group were ininjected intraperitoneally with captopril （1.25mg/kg） immediately following LPS administration. Six hours after lipopolysaccharide instillation, the rats in each group were killed for samples. The level of PaO2, wet/dry ratio（W/D）, the concentration of protein in bronchoalveolar lavage fluid （BALF） and lung tissue histopathological changes were examined. The activity of MPO in lung, the level of TNF-αin serum and BALF were measured respectively by chromometry, enzyme-linked immunosorbent assay （ELISA）. The datas were analysed by SAS 9.1 software.Results Histological examination showed that extensive lung inflammation were seen in the LPS group, which manifested by accumulation of significant numbers of neutrophils. The level of PaO2 decreased and the level of W/D, concentration of protein in BALF were increased significantly, together the activity of MPO in lung, the level of TNF-αin serum and BALF ascended （P<0.05）. Compared with LPS group these changes were markedly attenuated in captopril group （P<0.05）,together the level of PaO2 and pathological changes of the lung were also ameliorate.Conclusion Captopril have protective effects on acute lung injury induced by LPS. PART TWO Captopril suppresses expression of lectin-like oxidizedLD L receptor-1 in lung tissue of ALI ratObjective To study the expression of lectin-like oxidized LDL receptor-1 （LOX-1） in acute lung injury and the effect of captopril, to investigate the role of LOX-1 in acute lung injury （ALI） and preliminary intervention. Methods Sprague-Dawley rats were randomly divided into 3 groups, a saline control group, a lipopolysaccharide （LPS） groups （5mg/kg）, and a LPS+captopril group（1.25mg/kg）, each group 10 rats. The level of PaO2, wet/dry ratio（W/D）, the concentration of protein in bronchoalveolar lavage fluid （BALF） and lung tissue histopathological changes were examined. The activity of MPO in lung, the level of TNF-αin serum and BALF were measured respectively by chromometry and enzyme-linked immunosorbent assay （ELISA）. LOX-1 mRNA was detected by RT-PCR analysis,and the expression of lectin-like oxidized LDL receptor-1 （LOX-1） protein in lung was measured by western blot. The datas were analysed by SAS 9.1 software.Results Histological examination showed that extensive lung inflammation were seen in the LPS group, which manifested by accumulation of significant numbers of neutrophils. The level of PaO2 in LPS group decreased compared with sham group. The level of W/D, concentration of protein in BALF, the level of TNF-αin serum and BALF, the expression of LOX-1 mRNA and LOX-1 protein in LPS group were increased significantlyc compared with sham group（P<0.05）. Compared with LPS group these changes were markedly attenuated in captopril group （P<0.05）,together the level of PaO2 and pathological changes of the lung were also ameliorate in captopril group.Conclusion LOX-1 protein may be a role in the pathogenesis of acute lung injury; there is protective effect of captopril on ALI, which may result from inhibiting the expression of LOX-1 protein.

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