血管紧张素Ⅱ-2型受体激动剂对脂多糖诱导的急性肺损伤大鼠的影响  

Effect of angiotensinⅡtype 2 receptor agonist on rats with lipopolysaccharide-induced acute lung injury

作　　者：岳佳 臧思皓 曾庆繁 YUE Jia;ZANG Sihao;ZENG Qingfan(Department of Anesthesiology,Baiyun Hospital Affiliated to Guizhou Medical University,Guiyang 550014,Guizhou,China;School of Anesthesiology,Guizhou Medical University,Guiyang 550004,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550004

出　　处：《贵州医科大学学报》2025年第2期226-231,246,共7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);贵阳市科学技术基金项目(筑科合同2022-4-14-1)。

摘　　要：目的探讨血管紧张素Ⅱ-2型受体激动剂(AT2R agonists,C21)对脂多糖(lipopolysaccharide,LPS)诱导的急性肺损伤(acute lung injury,ALI)大鼠的影响。方法40只SD大鼠随机均分为对照组(等量生理盐水)、模型组(LPS 10 mg/kg)、治疗组(LPS 10mg/kg联合C211mg/kg)和抑制剂组[LPS 10mg/kg联合一氧化氮合酶抑制剂(nitric oxide synthase inhibitor,L-NAME)30mg/kg];造模8 h后开胸取大鼠新鲜右上肺组织测定湿/干比(W/D),采用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)测定肺组织中白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子(tumor necrosis factor,TNF-α)、IL-10、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)、血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)、血管紧张素Ⅱ-1型受体(angiotensinⅡ-1 receptor,AT1R)、血管紧张素Ⅱ-2型受体(angiotensinⅡ-2 receptor,AT2R)及一氧化氮(nitric oxide,NO)的含量;采用苏木精-伊红(hematoxylin eosin,HE)染色在光镜下观察肺组织病理学变化。结果与对照组比较,模型组W/D显著增加(P<0.05),IL-6、TNF-α、iNOS、AT1R、NO显著升高(P<0.05);肺泡细胞损伤增生呈复层结构,局部可见肺泡腔扩张,肺内动脉损伤,肺泡出血水肿,局部平滑肌缺失,间质可见结缔组织增生并伴有大量炎性细胞浸润,部分可见透明膜形成;与模型组比较,治疗组及抑制剂组W/D显著降低(P<0.05),IL-6、TNF-α、iNOS、AT1R、NO显著降低(P<0.05),IL-10、AT2R显著降低(P<0.05);镜下炎性细胞浸润明显减轻,肺泡和间质内的水肿和出血相对于模型组损伤明显减轻,水肿液吸收。结论C21可以减轻LPS诱导的ALI大鼠的炎症反应,其机制可能与减少iNOS、NO含量有关。Objective To explore the effect of angiotensinⅡ-2 receptor agonist(C21)on rats with lipopolysaccharide(LPS)-induced acute lung injury(ALI).Methods Forty SD rats were randomly divided into control group(equal amount of physiological saline),model group(LPS 10 mg/kg),treatment group(LPS 10 mg/kg combined with C211 mg/kg)and inhibitor group(LPS 10 mg/kg combined with nitric oxide synthase inhibitor(L-NAME)30mg/kg).After 8 hours of modeling,fresh right upper lung tissue from rats was taken by thoracotomy to determine the wet/dry ratio(W/D).Enzyme linked immunosorbent assay(ELISA)was applied to examine the contents of interleukin-6(IL-6),tumor necrosis factor(TNF-α),IL-10,inducible nitric oxide synthase(iNOS),angiotensinⅡ(AngⅡ),Ang II type 1 receptor(AT1R),AngⅡtype 2 receptor(AT2R),and nitric oxide(NO)in lung tissues.Hematoxylin and eosin(HE)staining was used to observe pathological changes in lung tissues.Results When compared to control group,model group had increased W/D ratio(P<0.05),remarkably elevated IL-6,TNF-α,iNOS,AT1R,and NO(P<0.05),and damaged alveolar cells proliferated and presented a multi-layered structure,with local alveolar cavity dilation,pulmonary artery injury,alveolar hemorrhage and edema,local smooth muscle loss,interstitial connective tissue proliferation accompanied by a large number of inflammatory cell infiltration and partial formation of transparent membranes.When compared to model group,treatment and inhibitor groups had significantly decreased W/D ratios(P<0.05),remarkably decreased IL-6,TNF-α,iNOS,AT1R,and NO(P<0.05),significantly decreased IL-10 and AT2R(P<0.05).Under microscope,the infiltration of inflammatory cells was seen to be significantly reduced,and the edema and bleeding in the alveoli and interstitia were significantly reduced when compared to model group.Edema fluid was absorbed.Conclusion C21 may alleviate the inflammatory response of LPS-induced ALI,and its mechanism may be related to reducing iNOS and NO contents.

关 键 词：急性肺损伤 血管紧张素Ⅱ-2型受体激动剂 诱导型一氧化氮合酶 一氧化氮合酶抑制剂 

分 类 号：R563.9[医药卫生—呼吸系统]