右美托咪定对内毒素急性肺损伤小鼠炎症反应的影响
陈秋霞, 刘流, 陈贵梅, 陈安基, 段柏情
金宝搏官方188附属长沙市妇幼保健院,长沙 410007
Effect of dexmedetomidine on inflammatory response in mice with acute lung injury induced by endotoxin
CHEN Qiuxia, LIU Liu, CHEN Guimei, CHEN Anji, DUAN Boqing
Changsha Hospital for Maternal and Child Health Care Affiliated to Hunan Normal Uiversity, Changsha 410007, China
摘要 目的: 研究右美托咪定(dexmedetomidine,DEX)对内毒素急性肺损伤小鼠的影响。方法: 32只健康雄性C57BL/6小鼠,随机分为4组(8只/组),假手术组(control组)、内毒素急性肺损伤组(LPS组)、高浓度DEX组(HD组)、低浓度DEX组(LD组)。Control组注射等容量生理盐水;LPS组腹腔注射LPS 3 mg/kg;DEX+LPS组在应用LPS前20分钟腹腔注射DEX(40 μg/kg或20 μg/kg)。病理组织切片检测肺组织炎症变化、测定肺湿重/干重比(W/D);酶联免疫吸附法(ELISA)检测血清IL-6、IL-8和IL-1β含量的变化;qRT-PCR检测肺组织中miR-155、miR-146a的变化。结果: 与control组比较,LPS组和DEX组肺组织炎症明显、肺W/D比值、IL-6、IL-8和IL-1β含量及miR-155表达水平升高、miR-146a表达水平降低;与LPS组比较,DEX组肺组织炎症明显好转、肺W/D比值、IL-6、IL-8和IL-1β含量及miR-155表达水平降低、miR-146a表达水平升高;与LD组比较HD组肺组织炎症明显好转、肺W/D比值、IL-6、IL-8和IL-1β含量及miR-155表达水平降低、miR-146a表达水平升高。结论: 右美托咪定(DEX)可减轻内毒素急性肺损伤小鼠炎症反应,且可能与miR-146a和miR-155有关。
关键词 :
右美托咪定 ,
内毒素急性肺损伤 ,
miR-146a ,
miR-155
Abstract :Objective Effect of dexmedetomidine (DEX) on endotoxin induced acute lung injury in mice. Methods 32 healthy male C57BL/6 mice were randomly divided into 4 groups (8 mice/group), sham operation group (control group), endotoxin acute lung injury group (LPS group), high concentration DEX group (HD group), low concentration DEX group (LD group). Control group was injected with saline of equal volume; LPS group was intraperitoneally injected with LPS 3 mg/kg; In DEX+LPS group, DEX (40 μg/kg or 20 μg/kg). The inflammatory changes of lung tissue and the ratio of wet weight to dry weight (W/D) were measured by pathological sections; Detection of serum IL-6, IL-8 and IL-1β by enzyme-linked immunosorbent assay (ELISA) Change of content; The changes of miR-155 and miR-146a in lung tissue were detected by qRT-PCR. Results Compared with control group, LPS group and DEX group had significant lung inflammation, lung W/D ratio, IL-6, IL-8, and IL-1β the content and expression level of miR-155 increased, while the expression level of miR-146a decreased (* P<0.05); Compared with LPS group, lung inflammation, lung W/D ratio, IL-6, IL-8, and IL-1β in DEX group were significantly improved the content and expression level of miR-155 decreased, while the expression level of miR-146a increased (# P<0.05); Compared with LD group, lung inflammation, lung W/D ratio, IL-6, IL-8, and IL-1β in HD group were significantly improved the content and expression level of miR-155 decreased, while the expression level of miR-146a increased ($ P<0.05). Conclusion Dextrmetomidine (DEX) can reduce the inflammatory reaction in mice with acute lung injury induced by endotoxin, which may be related to miR-146a and miR-155.
Key words :
demetomidine
acute lung injury caused by endotoxin
miR-146a
miR-155
收稿日期: 2023-01-29
基金资助: 湖南省临床医疗技术创新引导项目(2021SK53202),长沙市自然科学基金(kq2208477)
通讯作者:
陈安基,E-mail:7797936@qq.com;段柏情,E-mail:22757199@qq.com
引用本文:
陈秋霞, 刘流, 陈贵梅, 陈安基, 段柏情. 右美托咪定对内毒素急性肺损伤小鼠炎症反应的影响[J]. 金宝搏官方188学报(医学版), 2023, 20(3): 24-27.
CHEN Qiuxia, LIU Liu, CHEN Guimei, CHEN Anji, DUAN Boqing. Effect of dexmedetomidine on inflammatory response in mice with acute lung injury induced by endotoxin. HuNan ShiFan DaXue XueBao(YiXueBan), 2023, 20(3): 24-27.
链接本文:
http://yxb.hunnu.edu.cn/CN/ 或 http://yxb.hunnu.edu.cn/CN/Y2023/V20/I3/24
[1] Nova Z, Skovierova H, Calkovska A.Alveolar-Capillary Membrane-Related Pulmonary Cells as a Target in Endotoxin-Induced Acute Lung Injury[J]. Int J Mol Sci, 2019, 20(4): 831-851. [2] Xiang H, Hu B, Li Z, et al.Dexmedetomidine controls systemic cytokine levels through the cholinergic anti-inflammatory pathway[J]. Inflammation, 2019, 37(5): 1763-1770. [3] Jayachandran J, Srinivasan H, Mani KP.Molecular mechanism involved in epithelial to mesenchymal transition[J]. Arch Biochem Biophys, 2021, 7(10): 1084-1089. [4] Lu Q, Wu R, Zhao M, et al.miRNAs as Therapeutic Targets in Inflammatory Disease[J]. Trends Pharmacol Sci, 2019, 40(11): 853-865. [5] Mann M, Mehta A, Zhao JL, et al.An NF-κB-microRNA regulatory network tunes macrophage inflammatory responses[J]. Nat Commun, 2017, 8(1): 851-864. [6] 姜黎珊, 姚明, 杨茂宪, 等. 不同方式下气管内滴注脂多糖方法制作急性呼吸窘迫综合征大鼠模型[J]. 中华危重症医学杂志 (电子版), 2019, 12(02): 80-84. [7] 郑传明, 纪忠, 徐志鹏, 等. miR-146a通过调节IRAK1影响急性胰腺炎炎症自噬机制的研究[J]. 安徽医科大学学报, 2022, 57(08): 1251-1256. [8] 樊丰夷, 蓝天座, 杨旸, 等. miR-146a对急性痛风性关节炎大鼠炎症反应的影响及其可能机制[J]. 广西医学, 2022, 44(11): 1260-1264. [9] Huang Z, Liu X, Wu X, et al.MiR-146a alleviates lung injury caused by RSV infection in young rats by targeting TRAF-6 and regulating JNK/ERKMAPK signaling pathways[J]. Sci Rep, 2022, 12(1): 3481-3493. [10] Li G, Xu M, Wang H, et al.MicroRNA-146a overexpression alleviates intestinal ischemia/reperfusion-induced acute lung injury in mice[J]. Exp Ther Med, 2021, 22(3): 937-946. [11] Gan L, Sun T, Li B, et al.Serum miR-146a and miR-150 as Potential New Biomarkers for Hip Fracture-Induced Acute Lung Injury[J]. Mediators Inflamm, 2018, 8(10): 1359-1368. [12] 张勇. 右美托咪定调控miR-146a对脓毒症小鼠急性肺损伤的保护作用及机制[D]. 济南: 山东大学, 2019. [13] 黎鸿章, 杨坤, 刘玉文, 等. miR-155干预烧伤急性肺损伤模型大鼠: 核转录因子κB通路的变化[J]. 中国组织工程研究, 2020, 24(02): 204-208. [14] 顾晓丽, 陈芳. miR-155通过靶向SIRT1减轻脓毒症导致的急性肺损伤[J]. 标记免疫分析与临床, 2022, 29(03): 458-463. [15] 陈孝会, 谢冰, 邱丽霞. 血清miR-155水平与脓毒症患者炎症反应、病情严重程度及短期预后的关系[J]. 标记免疫分析与临床, 2022, 29(06): 1000-1006. [16] 郝金香, 许俊旭, 梁勇, 等. 急性肺损伤患者血浆miR-127及miR-155表达水平及对预后的影响[J]. 临床急诊杂志, 2020, 21(08): 654-658. [17] Zhang X, Liu X, Li Y, et al.Downregulation of microRNA-155 ameliorates high glucose-induced endothelial injury by inhibiting NF-κB activation and promoting HO-1 and NO production[J]. Biomedicine & Pharmacotherapy, 2017, 88(Complete): 1227-1234. [18] 席卓娜, 乔亚红, 程方圆. miR-146a和miR-155与慢性阻塞性肺疾病炎症表型的相关性分析[J]. 临床肺科杂志, 2020, 25(01): 78-88. [19] Han Y, Li Y, Jiang Y.The Prognostic Value of Plasma MicroRNA-155 and MicroRNA-146a Level in Severe Sepsis and Sepsis-Induced Acute Lung Injury Patients[J]. Clin Lab, 2016, 62(12): 2355-2360. [20] 何达, 张莉. 右美托咪定对急性肺损伤小鼠NLRP3炎性小体介导炎症反应的作用研究[J]. 广东药科大学学报, 2022, 38(06): 19-24. [21] 符新春, 陶敏, 徐晖, 等. 右美托咪定对高氧诱导急性肺损伤小鼠的保护作用及Nrf2/HO-1通路的影响[J]. 中国药师, 2019, 22(10): 1805-1810. [22] 董丽敏, 周南, 孙莹杰. 右美托咪定改善感染性休克大鼠急性肺损伤及对TLR9/NF-κB通路表达的影响[J]. 解剖科学进展, 2019, 25(06): 626-633. [23] 姜远旭, 詹美俊, 幸志强, 等. 右美托咪定通过α7nAChR介导的TLR4/NF-κB通路减轻脂多糖诱导的急性肺损伤[J]. 解放军医学杂志, 2021, 46(03): 231-237. [24] 陈胜阳, 张永强, 刘俊, 等. 右美托咪定激活PI3K/Akt通路改善LPS诱导的大鼠急性肺损伤实验研究[J]. 现代药物与临床, 2020, 35(11): 2123-2130.
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