血管紧张素Ⅱ1型受体拮抗剂用于脓毒症大鼠的实验研究

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。

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

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(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.