AT2R激动剂C21联合ACE2抑制剂对脓毒症大鼠炎症反应的影响  

Effects of AT2R agonist C21 combined with ACE2 inhibitor on inflammatory response in septic rats

作　　者：臧思皓 岳佳 曾庆繁 ZANG Sihao;YUE Jia;ZENG Qingfan(Department of Anesthesiology,Baiyun Hospital Affiliated to Guizhou Medical University,Guiyang 550014,Guizhou,China;School of Anesthesiology,Guizhou Medical University,Guiyang 550001,Guizhou,China)

机构地区：[1]贵州医科大学附属白云医院麻醉科,贵州贵阳550014 [2]贵州医科大学麻醉学院,贵州贵阳550001

出　　处：《贵州医科大学学报》2024年第9期1293-1298,共6页Journal of Guizhou Medical University

基　　金：贵州省科技计划项目(黔科合支撑〔2021〕一般098)。

摘　　要：目的探讨血管紧张素Ⅱ-2受体(AT2R)激动剂C21和血管紧张素转换酶2(ACE2)抑制剂联合作用对脂多糖(LPS)诱导的脓毒症大鼠全身炎症反应的影响。方法50只SD大鼠均分为对照组、实验组、治疗组、ACE2抑制组及联合组,除对照组外其余各组大鼠采用腹腔注射LPS构建脓毒症模型,其中治疗组、ACE2抑制组、联合组在注射LPS前分别注射C21、ACE2抑制剂(MLN-4760)及二者联合进行干预;干预结束8 h后,麻醉各组大鼠、取腹主动脉血,采用酶联免疫分析(ELISA)检测血清中肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)、IL-10、血管紧张素1受体(AT1R)、AT2R、血管紧张素Ⅱ(AngⅡ)及一氧化氮(NO)水平;取血后处死各组大鼠,取心脏和肾脏样本制作切片,采用HE染色观察心脏和肾脏组织学特征。结果与对照组比较,各组大鼠血清IL-6、IL-10、TNF-α、AngⅡ、AT1R及AT2R升高,实验组、ACE2抑制组、联合组NO升高(P<0.05);与实验组比较,治疗组、ACE2抑制组及联合组大鼠血清中IL-6、TNF-α、AT1R及AngⅡ降低、IL-10升高(P<0.05),治疗组、联合组联合组大鼠血清AT2R升高(P<0.05);与实验组比较,治疗组大鼠血清NO降低(P<0.05),ACE2抑制组NO升高(P<0.05);与治疗组比较,ACE2抑制组及联合组大鼠血清中IL-6、TNF-α、AT1R及NO升高(P<0.05),IL-10、AT2R降低(P<0.05);与ACE2抑制组比较,联合组大鼠血清中IL-6、TNF-α、AngⅡ及NO降低(P<0.05),IL-10、AT2R升高(P<0.05);与对照组比较,治疗组、实验组、ACE2抑制组及联合组大鼠心肌、肾脏细胞中可见炎症细胞浸润明显,但治疗组炎症细胞浸润较少,肾小管空泡变性、炎症细胞浸润较轻。结论AT2R激动剂C21联合ACE2抑制剂可减轻大鼠因高AT1R引起的炎症细胞浸润,其机制可能与血清AT1R、AT2R及AngⅡ影响炎症因子释放有关。Objective To investigate the effects of angiotensin 2 receptor(AT2R)agonist C21 and angiotensin-converting enzyme 2(ACE2)inhibitor on the systemic inflammatory response induced by lipopolysaccharide(LPS)in septic rats.Methods Fifty SD rats were equally divided into control group,experimental group,treatment group,ACE2 inhibition group,and combined group.Except for the control group,the other groups were injected intraperitoneally with LPS to induce a sepsis model.The treatment group,ACE2 inhibition group,and combined group were respectively injected with C21,ACE2 inhibitor(MLN-4760),and both agents before LPS injection.After 8 hours of intervention,the rats were anesthetized,and blood was collected from the abdominal aorta.Serum levels of tumor necrosis factor alpha(TNF-α),interleukin-6(IL-6),IL-10,angiotensin 1 receptor(AT1R),AT2R,angiotensinⅡ(AngⅡ),and nitric oxide(NO)were measured by enzyme-linked immunosorbent assay(ELISA).After blood collection,the rats were euthanized,and heart and kidney samples were taken for histological examination using HE staining to observe the histological characteristics.Results Compared with the control group,serum levels of IL-6,IL-10,TNF-α,AngⅡ,AT1R,and AT2R were significantly increased in all groups(P<0.05).The levels of NO were higher in the experimental group,ACE2 inhibition group,and combined group(P<0.05).Compared with the experimental group,serum levels of IL-6,TNF-α,AT1R,and AngⅡwere significantly lower,and IL-10 levels were higher in the treatment group,ACE2 inhibition group,and combined group(P<0.05).Serum AT2R levels were higher in the treatment and combined groups(P<0.05).NO levels were lower in the treatment group(P<0.05)and higher in the ACE2 inhibition group(P<0.05).Compared with the treatment group,serum levels of IL-6,TNF-α,AT1R,and NO were higher,and IL-10 and AT2R were lower in the ACE2 inhibition group and combined group(P<0.05).Compared with the ACE2 inhibition group,serum levels of IL-6,TNF-α,AngⅡ,and NO were lower,and IL-10 and AT2R were high

关 键 词：脓毒症 肾素-血管紧张素系统 血管紧张素Ⅱ 血管紧张素1受体 血管紧张素2受体 炎症因子 

分 类 号：R631.3[医药卫生—外科学]