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 of NF-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 ( ATIR ) antagonist on LPS-induced sepsis in rats.Methods Thirty male SD rats were randomly divided into 3groups ( 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 ( IKB ) 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 ( P＜ 0.01 ), which were markedly reduced in LOS group ( P ＜ 0.01 ).Both of the IκB mRNA and protein expressions in aortas were down-regulated after injection of LPS compared with the control group( P ＜ 0.01 ).However, in the LOS group,IκB mRNA and protein expressions in aortas were obviously higher than the LPS group( P ＜ 0.01 ).Conclusion AT1 receptor antagonist losartan exerts anti-inflammatory effects on sepsis rats.
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