血管紧张素Ⅱ1型受体拮抗剂用于脓毒症大鼠的实验研究  

Anti-inflammatory effect of losartan on LPS-induced sepsis in rats

作　　者：廖丽君[1] 郭建荣[1] 贾东林[2] 喻君[3] 沈华春[1] 

机构地区：[1]宁波大学医学院附属李惠利医院麻醉科,浙江宁波315040 [2]北京大学第三医院麻醉科,北京100083 [3]皖南医学院附属弋矶山医院麻醉科,安徽芜湖241001

出　　处：《中国药理学通报》2011年第10期1448-1451,共4页Chinese Pharmacological Bulletin

基　　金：宁波市医学科技基金资助项目(No200504)

摘　　要：目的观察血管紧张素Ⅱ1型受体拮抗剂氯沙坦对内毒素诱导的脓毒症大鼠的干预效果。方法 SD大鼠30只随机分成生理盐水对照组(Control组,n=10)、脓毒症组(LPS组,LPS 12 mg·kg-1,iv,n=10)和氯沙坦组(LOS组,氯沙坦50 mg·kg-1 ip,30 min后LPS 12 mg·kg-1 iv,n=10)。LPS注射6 h后抽血检测一氧化氮(NO)、丙二醛(MDA)及IL-1β、TNF-α血浆浓度,随即处死大鼠,分离胸主动脉,测定各组胸主动脉核因子κB抑制蛋白(inhibitor ofNF-κB,IκB)mRNA和蛋白的表达。结果 LPS组NO、MDA、IL-1β及TNF-α血浆浓度较对照组明显升高(P<0.01),经LOS干预后上述指标明显降低(P<0.01);大鼠胸主动脉IκB mRNA和蛋白在LPS组中的表达较对照组均明显降低(P<0.01),而LOS组中IκB的mRNA和蛋白表达较LPS组明显回升(P<0.01)。结论血管紧张素Ⅱ1型受体拮抗剂氯沙坦对内毒素诱导的脓毒症大鼠有抗炎作用。Aim The purpose of this study was to investigate role of angiotensin Ⅱ 1 receptor（AT1R） antagonist on LPS-induced sepsis in rats.Methods Thirty male SD rats were randomly divided into 3 groups（n=10 each）,rats were injected with 9 mg·ml-1 NaCl solution（Control group）,or received LPS 12 mg·kg-1 intravenously（LPS group）,or accepted infusion of an AT1 receptor antagonist,losartan 50 mg·kg-1 intraperitoneally 30 min before LPS 12 mg·kg-1 was intravenously administered（LOS group）.The plasma concentrations of nitric oxide（NO）,malondialdehyde（MDA）,IL-1β and TNF-α were measured in all rats 6 h after LPS administration,then all the rats were killed immediately before the aortas were removed and the inhibitor of NF-κB（IκB） mRNA and protein expressions in aortas were determined.Results The plasma concentrations of NO,MDA,IL-1β and TNF-α were all significantly elevated in LPS group compared with the control group（P0.01）,which were markedly reduced in LOS group（P0.01）.Both of the IκB mRNA and protein expressions in aortas were down-regulated after injection of LPS compared with the control group（P0.01）.However,in the LOS group,IκB mRNA and protein expressions in aortas were obviously higher than the LPS group（P0.01）.Conclusion AT1 receptor antagonist losartan exerts anti-inflammatory effects on sepsis rats.

关 键 词：脓毒症 血管紧张素Ⅱ1型受体 拮抗剂 内毒素 氯沙坦 IΚB 

分 类 号：R-332[医药卫生] R392.11