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腺苷A2A受体激动剂CGS21680对脂多糖诱导的小鼠急性肺损伤的保护作用
Protective effect of adenosine A2A receptor agonist CGS21680 on mice with lipopolysaccharide induced acute lung injury
【摘要】 目的:探讨腺苷A2A受体激动剂对脂多糖(LPS)诱导的急性肺损伤(ALI)小鼠的作用。方法:采用LPS(10 mg/kg)气管内注射6 h后的ALI小鼠模型。实验动物随机分为生理盐水对照组、ALI组、CGS21680治疗组和CGS21680对照组。测定各组6 h后肺湿重/干重比值(W/D)。比色法测定各组肺组织中髓过氧化物酶(MPO)活性。Western blotting分析各组肺组织中细胞间黏附分子1(ICAM-1)和血管细胞黏附分子1(VCAM-1)的表达。酶联免疫吸附法(ELISA)检测各组小鼠血清中单核细胞趋化蛋白1(MCP-1)的浓度。观察各组肺组织病理改变。结果:ALI组肺W/D、MPO活性、ICAM-1及VCAM-1表达和MCP-1浓度均较对照组显著升高。CGS21680治疗组前述各项指标较ALI组有显著下降。CGS21680组较对照组各项指标无显著差异。肺组织病理显示,ALI组可见肺间质明显充血水肿,大量炎症细胞浸润,部分肺泡腔内可见红细胞。CGS21680治疗组可显著改善肺组织的病理变化。结论:腺苷A2A受体激动剂CGS21680可明显减轻LPS诱导的ALI小鼠肺组织的炎症反应及肺组织水肿,提示腺苷A2A受体激动剂在急性肺损伤中具有保护作用。
【Abstract】 AIM: To investigate the effect of adenosine A2A receptor agonist on mice with acute lung injury(ALI) induced by lipopolysaccharide(LPS).METHODS: The mouse model of ALI was established by intraperitoneal injection of LPS.The mice were randomly divided into saline control group,ALI group,CGS21680 treatment group and CGS21680 control group.Six hours after LPS injection,the mice were sacrificed.The ratio of pulmonary wet weight to dry weight(W/D) was measured to assess the extent of pulmonary edema.Neutrophil infiltration was assayed by determining the myeloperoxidase(MPO) activity in lung tissues.The expression of intercellular adhesion molecule 1(ICAM-1) and vascular cell adhesion molecule 1(VCAM-1) was detected by Western blotting.The level of monocyte chemoattractant protein 1(MCP-1) in the serum was examined by ELISA.The pathological changes of the lung were observed.RESULTS: The lung W/D,MPO activity,the expression of ICAM-1 and VCAM-1 intercellular adhesion molecule 1(ICAM-1) and vascular cell adhesion molecule 1(VCAM-1),and the concentration of MCP-1 in ALI group were significantly higher than those in control group.All indexes reduced significantly in CGS21680 treatment group as compared with ALI group.No statistical difference between CGS21680 group and control groups was observed.Marked pulmonary interstitial hyperemia,edema,and infiltration of a large number of inflammatory cells and red blood cells were observed in some alveolar space in ALI group.Treatment with CGS21680 greatly improved the pathological changes of the lung tissues.CONCLUSION: Adenosine A2A agonist CGS21680 has a protective effect on mice with acute lung injury.
【Key words】 Acute lung injury; Lipopolysaccharides; Receptors,adenosine A2A;
- 【文献出处】 中国病理生理杂志 ,Chinese Journal of Pathophysiology , 编辑部邮箱 ,2013年04期
- 【分类号】R563.8
- 【被引频次】3
- 【下载频次】145