NLRP3的过度激活与ARDS和损伤性机械通气诱导的肺损伤的关系

摘要
图/表
参考文献(25)
相关文章 (15)

全文: PDF (1086 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要目的探讨核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎症小体是否参与急性呼吸窘迫综合征（ARDS）和损伤性机械通气诱导的肺损伤。方法 10只SD大鼠按随机数字表法分为生理盐水组（NS组，n = 5）和油酸组（OA组，n = 5），NS组和OA组分别经颈静脉注射0.1 mL/kg的NS和OA。2 h后通过氧合指数，肺损伤评分，肺湿/干重比（W/D），确定ARDS模型制备成功。另取40只雄性SD大鼠分为对照组（n = 10），OA组（n = 30）。麻醉后2 h后按通气方式不同，OA组分为ARDS组，小潮气量组（Vt = 6 mL/kg）、损伤性通气组（Vt = 20 mL/kg），每组10只。对照组和ARDS组保持自主呼吸，后两组给予机械通气。分别在麻醉后2、3、4、5、6 h采集颈动脉血行血气分析，6 h后测定W/D和肺损伤评分。RT-PCR和Western blot分别用于检测肺组织中NLRP3、半胱氨酸天冬氨酸酶（Caspase）-1、白细胞介素（IL）-1β、IL-18的mRNA及蛋白表达。结果 OA组W/D、肺损伤评分高于NS组，氧合指数低于NS组（P ＜ 0.01）。ARDS组肺损伤评分和W/D低于损伤性通气组，高于小潮气量组和对照组（均P ＜ 0.001）。ARDS组pH和氧合指数低于小潮气量组，高于损伤性通气组（均P ＜ 0.05）。ARDS组动脉血二氧化碳分压（PaCO2）高于损伤性通气组，低于小潮气量组（均P ＜ 0.05）。ARDS组NLRP3、Caspase-1、IL-1β和IL-18蛋白及mRNA表达低于损伤性通气组，高于对照组（均P ＜ 0.01）。ARDS组和小潮气量组的NLRP3、Caspase-1、IL-1β和IL-18的mRNA表达比较，差异无统计学意义（均P ＞ 0.05）。结论 NLRP3炎症小体过度激活参与了ARDS和损伤性机械通气诱导的肺损伤。损伤性机械通气进一步激活NLRP3炎症小体，加重肺损伤。小潮气量通气可避免NLRP3炎症小体的进一步激活。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	刘军石颖王婷婷左祥荣

关键词 ：急性呼吸窘迫综合征, 核苷酸结合寡聚化结构域样受体蛋白3炎症小体, 炎症, 机械通气

Abstract：Objective To investigate whether nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) inflammasome involved in acute respiratory distress syndrome (ARDS) and lung injury induced by invasive mechanical ventilation. Methods Ten SD rats were divided into normal saline group (NS, n = 5) and oleic acid group (OA, n = 5) according to random number table method. NS group and OA group were given 0.1 mL /Kg of NS and OA via jugular vein, respectively. Two hours later, the ARDS model was determined to be successful by oxygenation index, lung injury score and lung wet-to-dry weight ratio (W/D). Another 40 male SD rats were divided into control group (n = 10) and OA group (n = 30). Two hours after anesthesia, according to different ventilation mode, OA group was divided into ARDS group, neap tide volume group (VT = 6 mL/kg) and injury ventilation group (VT = 20 mL/kg), with 10 rats in each group. The control group and ARDS group maintained spontaneous breathing, and the latter two groups were given mechanical ventilation. Carotid blood was collected at 2, 3, 4, 5 h and 6 h after anesthesia for blood gas analysis, W/D and lung injury score 6 h later were measured. RT-PCR and Western blot were used to detect the mRNA and protein expressions of NLRP3, caspase-1, interleukin (IL)-1β and IL-18 in lung tissues, respectively. Results W/D and lung injury scores in OA group were higher than those in NS group, and oxygenation index was lower than that in NS group (P < 0.01). The lung injury score and W/D in ARDS group were lower than those in injury-induced ventilation group, and higher than those in neap tide volume group and control group (all P ＜ 0.01). The pH and oxygenation index of ARDS group were lower than those of neap tide volume group, and higher than those of injury ventilation group (all P ＜ 0.05). Arterial partial pressure of carbon dioxide (PaCO2) in ARDS group was higher than that in injury ventilation group and lower than that in neap tidal volume group (all P ＜ 0.05). The protein and mRNA expressions of NLRP3, caspase-1, IL-1β and IL-18 in ARDS group were lower than those in injury ventilation group and higher than those in control group (all P ＜ 0.01). The mRNA expression of NLRP3, caspase-1, IL-1β and IL-18 in ARDS group and neap tidal volume group had no statistical significance (all P ＞ 0.05). Conclusion Overactivation of NLRP3 inflammasome is involved in ARDS and lung injury induced by invasive mechanical ventilation, intrusive mechanical ventilation further activates NLRP3 inflammasomes and aggravates lung injury, neap tidal ventilation prevents further activation of NLRP3 inflammasomes.

Key words： Acute respiratory distress syndrome Nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome Inflammation Mechanical ventilation

基金资助:江苏省青年医学重点人才项目（QNRC2016557）；
江苏省第五期“333高层次人才培养工程”第三层次培养项目；
江苏省高层次卫生人才“六个一工程”拔尖人才科和全省人事人才管理课题（LGY2019067）。

通讯作者: 左祥荣（1978-），男，博士，主任医师，教授，硕士生导师；研究方向：肺动脉高压与右心衰竭。

作者简介: 刘军（1984-），男，南京医科大学第一临床学院2018级重症医学专业在读硕士研究生；研究方向：右心衰竭的基础研究。

引用本文:

刘军石颖王婷婷左祥荣. NLRP3的过度激活与ARDS和损伤性机械通气诱导的肺损伤的关系[J]. 中国医药导报, 2021, 18(18): 17-21.
LIU Jun SHI Ying WANG Tingting ZUO Xiangrong. Overactivation of nucleotide-binding oligomerization domain-like receptor protein 3 is involved in lung injury induced by acute respiratory distress syndrome and injurious mechanical ventilation. 中国医药导报, 2021, 18(18): 17-21.

链接本文:

https://www.yiyaodaobao.com.cn/CN/ 或 https://www.yiyaodaobao.com.cn/CN/Y2021/V18/I18/17

[1] Bellani G，Laffey JG，Pham T，et al. Epidemiology，patterns of care，and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries [J]. JAMA，2016，315（8）：788-800.
[2] Fan E，Brodie D，Slutsky AS. Acute respiratory distress syndrome：advances in diagnosis and treatment [J]. JAMA，2018，319（7）：698-710.
[3] Marco V，Ranieri，Gordon D，et al. Acute respiratory distress syndrome：the Berlin Definition [J]. JAMA，2012，307（723）：2526-2533.
[4] Szabari MV，Takahashi K，Feng Y，et al. Relation between respiratory mechanics，inflammation，and survival in experimental mechanical ventilation [J]. Am J Respir Cell Mol Biol，2019，60（2）：179-188.
[5] Mauri T，Lazzeri M，Bellani G，et al. Respiratory mechanics to understand ARDS and guide mechanical ventilation [J]. Physiol Meas，2017，38（12）：280-303.
[6] 张维康，潘灵辉.NOD样受体蛋白3炎症小体在呼吸机相关性肺损伤中的作用机制研究[J].中华危重病急救医学，2015（10）：821-825.
[7] Chambers ED，White A，Vang A，et al. Blockade of equilibrative nucleoside transporter 1/2 protects against Pseudomonas aeruginosa-induced acute lung injury and NLRP3 inflammasome activation [J]. FASEB J，2020，34（1）：1516-1531.
[8] Cao F，Tian X，Li Z，et al. Suppression of NLRP3 inflammasome by erythropoietin via the EPOR/JAK2/STAT3 pathway contributes to attenuation of acute lung injury in mice [J]. Front Pharmacol，2020，11：306.
[9] Zhou Y，Zhang CY，Duan J X，et al. Vasoactive intestinal peptide suppresses the NLRP3 infl the NLRP3 inflammasome activation in lipopolysaccharide-induced acute lung injury mice and macrophages [J]. Biomed Pharmacother，2020，121：109596.
[10] Lamkanfi M，Dixit VM. Mechanisms and functions of inflammasomes [J]. Cell，2014，157（5）：1013-1022.
[11] Jo EK，Kim JK，Shin DM，et al. Molecular mechanisms regulating NLRP3 inflammasome activation [J]. Cell Mol Immunol，2016，13（2）：148-159.
[12] 潘徐彪，李向玉，王志鑫，等.NLRP3-（Caspase-1）/IL-1β信号通路的研究进展[J].中国医药导报，2019，16（1）：47-50.
[13] Jorgensen I，Miao EA. Pyroptotic cell death defends against intracellular pathogens [J]. Immunol Rev，2015， 265（1）：130-142.
[14] Boehm O，Rohner M，Ehrentraut H，et al. Low-tidal-volume prevent ventilation induced inflammation in a mouse model of sepsis [J]. Life Sci，2020，240：117081.
[15] Pan L，Yao DC，Yu YZ，et al. Activation of necroptosis in a rat model of acute respiratory distress syndrome induced by oleic acid [J]. Sheng Li Xue Bao，2016，68（5）：661-668.
[16] Yan X，Li Y，Choi YH，et al. Protective effect and mechanism of alprostadil in acute respiratory distress syndrome induced by oleic acid in rats [J]. Med Sci Monit，2018，24：7186-7198.
[17] Matute-Bello G，Downey G，Moore BB，et al. An official American Thoracic Society workshop report：features and measurements of experimental acute lung injury in animals [J]. Am J Respir Cell Mol Biol，2011，44（5）：725-738.
[18] Repessé X，Charron C，Vieillard-Baron A. Acute respiratory distress syndrome：the heart side of the moon [J]. Curr Opin Crit Care，2016，22（1）：38-44.
[19] Swanson KV，Deng M，Ting JP. The NLRP3 inflammasome：molecular activation and regulation to therapeutics [J]. Nat Rev Immunol，2019，19（8）：477-489.
[20] 张本旺，蒋娟，马福国，等.亚甲蓝对大鼠机械通气相关肺损伤中核苷酸结合寡聚化结构域样受体蛋白3炎性小体的影响[J].临床麻醉学杂志，2020，36（8）：793-798.
[21] Kellner M，Noonepalle S，Lu Q，et al. ROS signaling in the pathogenesis of acute lung injury （ALI） and acute respiratory distress syndrome （ARDS）[J]. Adv Exp Med Biol，2017，967：105-137.
[22] 许宝胜，刘洪涛，冶国栋，等.基于Keap1/Nfr2/ARE信号通路研究机械相关性肺损伤分子机制[J].四川大学学报：医学版，2019，50（3）：317-322.
[23] Kelley N，Jeltema D，Duan Y，et al. The NLRP3 inflammasome：an overview of mechanisms of activation and regulation [J]. Int J Mol Sci，2019，20（13）：3328.
[24] Howrylak JA，Nakahira K. Inflammasomes：key mediators of lung immunity [J]. Annu Rev Physiol，2017，79：471-494.
[25] 张志权，孙玲玲.IL-1β与IL-18在急性肺损伤中的表达及临床意义[J].海南医学，2017，28（12）：1954-1956.