氯沙坦抑制急性肺损伤大鼠肺组织LOX-1表达  

Losartan suppresses expression of lectin-like oxidized LDL receptor-1 in lung tissue of ALI rat

作　　者：韩鹏凯[1] 张婷[1] 王导新[1] 

机构地区：[1]重庆医科大学第二附属医院呼吸内科,重庆400010

出　　处：《基础医学与临床》2011年第3期281-285,共5页Basic and Clinical Medicine

基　　金：重庆市卫生局医学科研项目计划(2008-2-224)

摘　　要：目的研究氯沙坦干预大鼠急性肺损伤模型肺组织血凝素样氧化低密度血浆脂蛋白受体-1(LOX-1)表达的变化,探讨LOX-1在急性肺损伤中的表现及氯沙坦的干预机制。方法将大鼠随机分成:对照组、脂多糖(LPS)组(5 mg/kg)及氯沙坦治疗组(8 mg/kg),每组10只。检测动脉血氧分压(PaO2)、肺湿/干质量值(W/D)、支气管肺泡灌洗液(BALF)蛋白含量、血浆和BALF中TNF-α水平及肺组织病理变化,比色法测定肺组织髓过氧化物酶(MPO)活性,用RT-PCR法检测肺组织LOX-1mRNA水平,Western blot法检测肺组织中LOX-1、ICAM-1、Cleavedcaspase-3蛋白的表达。结果脂多糖处理后大鼠肺部炎性反应显著,PaO2较对照组下降,而肺W/D值、BALF蛋白含量及TNF-α水平、血浆TNF-α水平、MPO活性升高(P<0.05);LOX-1mRNA和LOX-1、ICAM-1及Cleavedcaspase-3蛋白表达升高(P<0.05)。氯沙坦显著缓解上述变化(P<0.05)。结论氯沙坦可能通过抑制LOX-1介导的炎性反应及细胞凋亡减轻急性肺损伤。Objective To study the effect of losartan on the expression of lectin-like oxidized LDL receptor-1（LOX-1） protein in acute lung injury（ALI） and to investigate its mechanism.Methods Rats were randomly divided into control group,lipopolysaccharide（LPS） group（5 mg/kg）,and LPS＋Losartan group.Rats in LPS＋Losartan group were given an intraperitoneal injection of losartann（8 mg/kg） after LPS administration.The level of PaO_2,wet/dry ratio（W/D）,the concentration of protein and TNF-α in bronchoalveolar lavage fluid（BALF）,TNF-α concentration in plasma,lung MPO（myeloperoxidase） activity and lung tissue histopathological changes were examined,LOX-1 mRNA was detected by RT-PCR analysis,the expression of LOX-1,ICAM-1,cleaved caspase-3 protein in lung was measured by Western blot.Results Histological examination showed extensive lung inflammation in the LPS group.The level of PaO_2 in LPS group decreased as compared with taht in sham group（P0.05）.The level of W/D,concentration of protein in BALF,TNF-α in BALF and plasma,lung MPO activity,the expression of LOX-1 mRNA,LOX-1,ICAM-1 and cleaved caspase-3 protein in LPS group significantlyincreased.Conclusion There is protective effect of losartan on ALI,which may result from inhibiting the inflammation and apoptosis induced by LOX-1.

关 键 词：急性肺损伤 氯沙坦 血凝素样氧化低密度血浆脂蛋白受体-1 

分 类 号：R965[医药卫生—药理学]