«上一篇/Previous Article|本期目录/Table of Contents|下一篇/Next Article»

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

28卷

期数:

2022年01期

页码:

65

栏目:

基础研究

出版日期:

2022-01-20

文章信息/Info

Title:

Inhibitory effect of dexmedetomidine on serum matrix metalloproteinase 7 in mice with septic acute lung injury

文章编号:

1006-8147（2022）01-0065-05

作者:

齐颖; 陈兵

（天津医科大学第二医院ICU，天津 300211）

Author(s):

QI Ying; CHEN Bing

（Department of Critical Care Medicine，The Second Hospital，Tianjin Medical University，Tianjin 300211，China）

关键词:

右美托咪定; 基质金属蛋白酶; 脓毒症; 急性肺损伤

Keywords:

dexmedetomidine; matrix metalloproteinases; sepsis; acute lung injury

分类号:

R781.4

DOI:

-

文献标志码:

A

摘要:

目的：探讨右美托咪定对脓毒症急性肺损伤（ALI）小鼠基质金属蛋白酶7（MMP7）的抑制作用。方法：制备脓毒症致ALI模型，将昆明小鼠随机分为对照组和ALI组及治疗组，每组32只；损伤组及治疗组腹腔注射大肠杆菌脂多糖10 mg /kg ，治疗组在注射脂多糖后给予腹腔注射右美托咪定25 μg/kg，对照组仅注射等剂量生理盐水，并按损伤时间点分为1、3、5、8 h。到达相应时间点后，待小鼠麻醉完全后从内龇取血，低温离心留取血清备用，待测定血MMP7浓度的变化，留取右肺下叶行苏木素伊红染色，取下的肺组织放置在10%福尔马林溶液中。右肺中叶和上叶组织进行肺组织匀浆提取蛋白，左肺组织浸泡在2.5%戊二醛中待行染色。结果：治疗组炎性细胞渗出减少，ALI组肺结构破坏严重，炎性细胞渗出增多；电镜下观察肺血管内皮细胞损伤程度，治疗组血管内皮细胞损伤程度较ALI组减轻；治疗组MMP7血清浓度较ALI组降低，对照组及治疗组血清MMP7浓度均低于ALI组，各组间差异有统计学意义（P ＜0.01）；Western结果显示，在损伤3 h时，ALI组MMP7表达较高，治疗组较ALI 组相比MMP7表达下降，差异具有统计学意义（P＜0.01）。结论：右美托咪定在一定程度上能抑制脓毒症ALI小鼠血清MMP7的产生。

Abstract:

Objective：To evaluate the inhibitory effect of dexmedetomidine on matrix metalloproteinase 7（MMP7） in mice with septic acute lung injury. Methods： The sepsis-induced acute lung injury animal model was established，and KM mice were randomly divided into control group，acute lung injury（ALI） group，and treatment group，with 32 mice in each group. The mice in injury group and treatment group were injected E.coli lipopolysaccharide（LPS） 10 mg/kg through intraperitoneal administration，the treatment group was given intraperitoneal injection of dexmedetomidine 25 μg/kg after lipopolysaccharide injection，and the control group was injected with the same dose of normal saline，and each group were divided into 4 subgroups according to different injury time points：1 h，3 h，5 h，8 h. After reaching the corresponding time point，when the mice were completely anesthetized，blood was taken from the inner canthus，and the serum was centrifuged at low temperature for reserve，the changes of MMP7 was measured. The lower lobe of the right lung was left for hematoxylin and eosin（HE） staining，and the lung tissue was removed and placed in 10% formalin solution. The middle and upper lobe tissues of the right lung were homogenized to extract protein，and the left lung tissue was immersed in 2.5% glutaraldehyde for electron staining. Results：In the treatment group，inflammatory cell exudation decreased，while in the ALI group，lung structure was severely damaged and inflammatory cell exudation increased. The injury of pulmonary vascular endothelial cells was observed by electron microscopy，and the injury degree of vascular endothelial cells in the treatment group was less than that in the ALI group. The serum concentration of MMP7 in the treatment group was lower than that in the ALI group. The concentration of serum MMP7 in control group and treatment group was lower than that in ALI group. There was statistically significant difference among each group（P<0.01）. Western blotting showed that the expression of MMP7 was higher in ALI group at 3 h after injury. The expression of MMP7 in the treatment group was lower than that in the ALI group（P<0.01）. Conclusion：Dexmedetomidine can suppress the expression of serum MMP7 in mouse model of ALI caused by sepsis to a certain extent.

参考文献/References:

[1] CABRAL-PACHECO G A，GARZA-VELOZ I，CASTRUITA-DE LA ROSA C，et al. The roles of matrix metalloproteinases and their inhibitors in human diseases[J]. Int J Mol Sci，2020，21（24）：9739.
[2] GHEIBI S，ALA S，HEYDARI F，et al. Evaluating the effect of dexmedetomidine on hemodynamic status of patients with septic shock admitted to intensive care unit：a single-blind randomized controlled trial[J]. Iran J Pharm Res，2020，19（4）：255-263.
[3] KUMAR P，SIRIPINI S，SREEDHAR A S. The matrix metalloproteinase 7（MMP7） links Hsp90 chaperone with acquired drug resistance and tumor metastasis[J]. Cancer Rep（Hoboken），2020，6：e1261.
[4] 罗红敏. 右美托咪定对需机械通气的脓毒症患者病死率及无机械通气天数的影响：一项随机对照试验 [J]. 中华危重病急救医学，2017，29（7）：632.
[5] ZHENG D，ZHANG J，ZHANG Z，et al. Endothelial microvesicles induce pulmonary vascular leakage and lung injury during sepsis [J]. Front Cell Dev Biol，2020，8：643.
[6] LI L C，TIAN Y，XIAO J，et al. Dexmedetomidine promotes inflammation resolving through TGF-beta1 secreted by F4/80（+）Ly6G（+） macrophage [J]. Int Immunopharmacol，2021，95：107480.
[7] MEI B，LI J，ZUO Z. Dexmedetomidine attenuates sepsis-associated inflammation and encephalopathy via central alpha2A adrenoceptor[J]. Brain Behav Immun，2021，91：296-314.
[8] 陈显峰，胡军涛，张驰，等.右美托咪定镇静对脓毒症并发ARDS患者肺保护作用的研究[J]. 中华危重病急救医学，2018，30（2）：151-155.
[9] SERRA R. Matrix metalloproteinases in health and disease[J]. Biomolecules，2020，10（8）：1138.
[10] MAATTA M，LAURILA H P，HOLOPAINEN S，et al. Matrix metalloproteinase-2，-7，and -9 activities in dogs with idiopathic pulmonary fibrosis compared to healthy dogs and dogs with other respiratory diseases [J]. J Vet Intern Med，2021，35（1）：462-471.
[11] 张延卓，何绪雄，叶茂英，等. 右美托咪定神经保护作用机制的综述[J]. 中国继续医学教育，2021，13（9）：195-198.
[12] YANG T，FENG X，ZHAO Y，et al. Dexmedetomidine enhances autophagy via α2-AR/AMPK/mTOR pathway to inhibit the activation of NLRP3 inflammasome and subsequently alleviates lipopolysaccharide-induced acute kidney injury[J]. Front Pharmacol，2020，11：790.
[13] YADAV P K，GUPTA S K，KUMAR S，et al. MMP-7 derived peptides with MHC class-Ⅰ binding motifs from canine mammary tumor tissue elicit strong antigen-specific T-cell responses in BALB/c mice[J]. Mol Cell Biochem，2021，476（1）：311-320.
[14] SOLUN B，SHOENFELD Y. Inhibition of metalloproteinases in therapy for severe lung injury due to COVID-19[J]. Med Drug Discov，2020，7：100052.
[15] ZHANG P，PENG J，REN Y Q，et al. Dexmedetomidine protects against endothelial injury in septic rats induced by cecal ligation and puncture by decreasing angiopoietin 2 and increasing vascular endothelial cadherin levels[J]. Exp Ther Med，2021，21（2）：111.

相似文献/References:

[1]刘文东,李英娴,娄婷婷,等.青蒿琥酯对肝纤维化大鼠肝组织基质金属蛋白酶表达的影响[J].天津医科大学学报,2013,19(05):362.
[2]田原,马跃美,刘艳荣,等.炎症因子IL-23对黑色素瘤B16F10细胞增殖和侵袭能力的影响[J].天津医科大学学报,2014,20(01):8.
　TIAN Yuan,MA Yue-mei,LIU Yan-rong,et al.Effects of IL-23 on proliferation and invasion of B16 melanoma cells[J].Journal of Tianjin Medical University,2014,20(01):8.
[3]王 鹏.右美托咪定预处理对止血带性心肌损伤的保护作用[J].天津医科大学学报,2016,22(01):64.
[4]王 鹏,李庆丰,林 红,等.右美托咪定联合罗哌卡因局部浸润对鼻内镜手术后镇痛的影响[J].天津医科大学学报,2016,22(05):457.
[5]张婷婷,张广华.右美托咪定持续输注对结肠癌手术麻醉的影响[J].天津医科大学学报,2017,23(01):62.
[6]贾智,周 游 综 述,赵梦明 审校.口腔复合树脂粘接剂的研究进展[J].天津医科大学学报,2017,23(02):182.
[7]陈 鹏,王 鹏.超声引导胸椎旁神经阻滞用于非体外循环冠脉旁路移植术患者超前镇痛的效果[J].天津医科大学学报,2017,23(05):453.
[8]黄庆先,王鹏.右美托咪定对行肿瘤细胞减灭术联合术中腹腔热灌注化疗老年患者术后认知功能的影响[J].天津医科大学学报,2018,24(02):174.
[9]李萌,房怿,刘洪霞,等.心率变异性分析对右美托咪定术前抗焦虑作用评价[J].天津医科大学学报,2022,28(01):77.
　LI Meng,FANG Yi,LIU Hong-Xia,et al.Analysis of heart rate variability evaluate dexmedetomidine for preoperative anxiety[J].Journal of Tianjin Medical University,2022,28(01):77.
[10]于乐昌,杨立恒,张蔷.右美托咪定对老年脓毒症机械通气患者炎症和预后的影响[J].天津医科大学学报,2022,28(04):409.
　YU Le-chang,YANG Li-heng,ZHANG Qiang.Effect of dexmedetomidine on inflammation and prognosis in elderly patients with sepsis requiring mechanical ventilation[J].Journal of Tianjin Medical University,2022,28(01):409.

备注/Memo

备注/Memo:

作者简介 齐颖（1985-），女，医师，硕士，研究方向：脓毒症急性肺损伤；通信作者：陈兵，Email：tisheng2008@163.com。

常用功能

更新日期/Last Update: 2022-01-20