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电针通过NLRP3/caspase-1通路介导的细胞焦亡途径减轻脓毒症大鼠急性肺损伤

  • 张昊

    机 构：

    天津医科大学南开临床学院（天津市南开医院）麻醉与重症医学科（天津 300100 ）

    ×
  • ，苏乾

    机 构：

    天津医科大学南开临床学院（天津市南开医院）麻醉与重症医学科（天津 300100 ）

    ×
  • ，史佳

    机 构：

    天津医科大学南开临床学院（天津市南开医院）麻醉与重症医学科（天津 300100 ）

    ×
  • ，宫丽荣

    机 构：

    天津医科大学南开临床学院（天津市南开医院）麻醉与重症医学科（天津 300100 ）

    ×

天津医科大学南开临床学院（天津市南开医院）麻醉与重症医学科（天津 300100 ）；

Electroacupuncture attenuates acute lung injury induced by sepsis via NLRP3/caspase-1 pathway mediated pyrocytosis pathway

  • Zhang Hao

    Affiliation：

    Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin( 300100 ),China

    ×
  • ，Su Qian

    Affiliation：

    Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin( 300100 ),China

    ×
  • ，Shi Jia

    Affiliation：

    Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin( 300100 ),China

    ×
  • ，Gong Li-rong

    Affiliation：

    Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin( 300100 ),China

    ×

Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin( 300100 ),China；

通讯作者:

宫丽荣，E-mail：soundglr@163.com

中图分类号:R655.3；R245.31

文献标识码:A

DOI:10.3969/j.issn.1007-6948.2023.06.017

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Li H,Qiu D,Yang H,et al.Therapeutic efficacy of excretory-secretory products of Trichinella spiralis adult worms on Sepsis-induced acute lung injury in a mouse model[J].Front Cell Infect Microbiol,2021,11:653843.
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参考文献 9
Zheng X,Wan J,Tan G.The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in diabetic retinopathy[J].Front Immunol,2023,14:1151185.
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参考文献 10
Guo J,Luo Y,Zuo J,et al.Echinacea polyphenols inhibit NLRP3-dependent pyroptosis,apoptosis,and necroptosis via suppressing NO production during lipopolysaccharide-induced acute lung injury[J].J Agric Food Chem,2023,71(19):7289-7298.
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参考文献 11
Han Z,Ma J,Han Y,et al.Irisin attenuates acute lung injury by suppressing the pyroptosis of alveolar macrophages[J].Int J Mol Med,2023,51(4):32.
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参考文献 12
Liu Y,Zhou J,Luo Y,et al.Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo[J].Chin Med,2021,16(1):127.
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参考文献 13
Zeng YJ,Qin QW,Li KY,et al.PKR suppress NLRP3-pyroptosis pathway in lipopolysaccharide-induced acute lung injury model of mice[J].Biochem Biophys Res Commun,2019,519(1):8-14.
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参考文献 14
Jiang HC,Shang Z,You LP,et al.Electroacupuncture pretreatment at Zusanli(ST36)ameliorates hepatic ischemia/reperfusion injury in mice by reducing oxidative stress via activating vagus nerve-dependent Nrf2 pathway[J].J Inflamm Res,2023,16:1595-1610.
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参考文献 15
Dong SA,Gong LR,Yu JB,et al.The role of melatonin in electroacupuncture alleviating lung injury induced by limb ischemia-reperfusion in rabbits[J].Med Sci Monit,2020,26:e922525.
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参考文献 16
Gong LR,Kan YX,Lian Y,et al.Electroacupuncture attenuates limb ischemia-reperfusion-induced lung injury via p38 mitogen-activated protein kinase-nuclear factor erythroid-2-related factor-2/heme oxygenase pathway[J].J Surg Res,2020,246:170-181.
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参考文献 17
宫丽荣,董树安,阚永星,等.α7烟碱型乙酰胆碱受体在电针减轻肢体缺血再灌注兔肺损伤中的作用[J].中国中西医结合外科杂志,2019,25(4):443-447.
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目录contents

    摘要

    目的：观察电针足三里穴和肺俞穴是否通过NLRP3/caspase-1通路介导的细胞焦亡途径减轻脓毒症诱导的大鼠急性肺损伤。方法：成年健康雄性SD大鼠30只，采用随机数字表法分为5组：对照组、模型组、电针组、电针+NLRP3激活剂组、非经非穴电针组，每组6只。采用盲肠结扎穿孔法建立脓毒症模型。电针组选取双侧足三里穴和肺俞穴给予疏密波电针刺激（模型制备前5 d每天进行1次，模型制备过程中每6 h进行1次，30 min/次）；非经非穴电针组以相同的参数电针刺激足三里穴和肺俞穴旁开5 mm非经非穴处。于模型制备前30 min电针+NLRP3激活剂组腹腔注射100 mg/kg尼日利亚菌素钠盐。建模后24 h时处死大鼠取肺组织，计算肺湿重/干重(W/D)比值，观察病理学结果并行肺损伤评分；采用ELISA法测定肺组织白细胞介素（IL）-1β、IL-18含量；采用Western blot法检测肺组织核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）、凋亡相关斑点样蛋白（ASC）、裂解的半胱氨酰天冬氨酸特异性蛋白酶-1（cleaved-Caspase-1)、N端消皮素-D（gasdermin D，GSDMD-N）蛋白的表达水平。结果：与对照组比较，模型组、电针组、电针+NLRP3激活剂组和非经非穴电针组肺损伤评分、W/D比值、IL-1β含量及IL-18含量均升高，肺组织NLRP3、ASC、cleaved-Caspase-1及GSDMD-N蛋白表达均上调，差异有统计学意义（P＜0.05）；与模型组比较，电针组肺损伤评分、W/D比值、IL-1β含量及IL-18含量均降低，肺组织NLRP3、ASC、cleaved-Caspase-1及GSDMD-N蛋白表达均下调，差异有统计学意义（P＜0.05）；与电针组比较，电针+NLRP3激活剂组肺损伤评分、W/D比值、IL-1β含量及IL-18含量均升高，肺组织NLRP3、ASC、cleaved-Caspase-1及GSDMD-N蛋白表达均上调，差异有统计学意义（P＜0.05）。结论：电针刺激足三里穴和肺俞穴减轻大鼠脓毒症急性肺损伤的机制可能与抑制NLRP3/caspase-1通路介导的经典细胞焦亡途径有关。

    Abstract

    Objective To observe whether electroacupuncture at Zusanli (ST36) and Feishu (BL13) acupoints reduces sepsis induced acute lung injury in rats through the pyroptosis pathway mediated by NLRP3/caspase-1 pathway. Methods Thirty adult healthy male SD rats were randomly divided into five groups: control group, model group, electroacupuncture group,electroacupuncture plus NLRP3 activator group, and non-acupoint electroacupuncture group, with six rats in each group. The sepsis model was established by cecal ligation and puncture. In the electroacupuncture group, bilateral ST36 and BL13 acupoints were stimulated with dense and sparse wave electroacupuncture (once daily for 5 days before model preparation, once every 6 hours during model preparation, 30 minutes each time). In the non-acupoint electroacupuncture group, the same parameters of electroacupuncture were applied at non-acupoints located 5mm away from ST36 and BL13. The electroacupuncture plus NLRP3 activator group received intraperitoneal injection of 100mg/kg nigericin sodium salt 30 minutes before model preparation. After modeling, the rats were sacrificed at 24 hours, and lung tissues were collected to calculate the wet-to-dry weight ratio (W/D ratio), observe pathological changes, and evaluate lung injury scores. The levels of IL-1β, IL-18 in lung tissues were measured by ELISA, and the expression levels of NLRP3, ASC, cleaved caspase-1, and GSDMD-N proteins in lung tissues were detected by Western blot. Results Compared with the control group, the lung injury scores, W/D ratio, IL-1β and IL-18 levels in the model group, electroacupuncture group, electroacupuncture plus NLRP3 activator group, and non-acupoint electroacupuncture group were increased. The expressions of NLRP3, ASC, cleaved caspase-1, and GSDMD-N proteins in lung tissues were upregulated, and the differences were statistically significant (P<0.05). Compared with the model group, the lung injury scores, W/D ratio, IL-1β and IL-18 levels in the electroacupuncture group were decreased. The expressions of NLRP3, ASC, cleaved caspase-1, and GSDMD-N proteins in lung tissues were downregulated, and the differences were statistically significant (P<0.05). Compared with the electroacupuncture group, the lung injury scores, W/D ratio, IL-1β and IL-18 levels in the electroacupuncture plus NLRP3 activator group were increased. The expressions of NLRP3, ASC, cleaved caspase-1, and GSDMD-N proteins in lung tissues were upregulated, and the differences were statistically significant (P<0.05). Conclusion Electroacupuncture stimulation at ST36 and BL13 acupoints may alleviate acute lung injury in rats with sepsis through inhibiting the classical cell pyroptosis pathway mediated by NLRP3/caspase-1 pathway.

  • 脓毒症急性肺损伤（acutelunginjury，ALI）是临床常见的急危重症，发病机制复杂且尚未完全阐明，尽管有关脓毒症急性肺损伤的研究及治疗措施已取得一定进展，但目前仍缺乏有效的特异性防治策略，其病死率仍高达40%[1-2]。本课题组前期研究发现，电针刺对脓毒症导致的急性肺损伤有保护作用，但具体作用机制尚不明确[3]。研究表明，核苷酸结合寡聚化结构域样受体蛋白3（nucleotide-binding oligomerization domain-like receptor protein 3，NLRP3）/半胱氨酰天冬氨酸特异性蛋白酶-1（caspase-1）/消皮素-D（gasdermin D，GSDMD）介导的经典焦亡信号通路的过度激活参与脓毒症诱导肺损伤的发生发展[4]。本研究旨在观察电针足三里穴和肺俞穴对脓毒症诱导急性肺损伤大鼠肺组织经典细胞焦亡通路的影响。

  • 1 材料与方法

  • 1.1 动物和试剂

  • 清洁级健康成年雄性SD大鼠30只。体质量200～220 g，7～8周龄，购自北京维通利华实验动物技术有限公司。G6805-1A低频电子脉冲治疗仪（上海华谊医用仪器有限公司），蛋白提取试剂盒、BCA蛋白定量试剂盒（美国Thermo公司）、NLRP3一抗（1∶2000）、凋亡相关斑点样蛋白（ASC）一抗（1∶2000）、N端消皮素D（GSDMD-N）一抗（1∶2000）以及IL-1β、IL-18 ELISA试剂盒均购自美国Abcam公司，裂解的半胱氨酰天冬氨酸特异性蛋白酶-1（cleaved-Caspase-1）一抗（1∶2000）购自美国CST公司，β-actin一抗、DAB显色试盒（美国Santa Cruz公司），山羊抗兔IgG二抗（1∶3000，美国Sigma公司），尼日利亚菌素钠盐（北京索莱宝科技有限公司）。本研究经我院医学伦理委员会备案并审批通过。

  • 1.2 分组和模型建立

  • 选取30只SD大鼠，采用随机数字表随机分为对照组、模型组、电针组、电针+NLRP3激活剂组、非经非穴电针组（每组n=6）。参照文献[5]中的方法，采用盲肠结扎穿孔术（CLP）制备脓毒症急性肺损伤模型。大鼠麻醉后行皮肤正中线约2 cm的纵行切口，充分暴露盲肠并于远端极点到底部距离的约一半处用3.0缝线结扎盲肠；在结扎处中间区域用20G无菌针头单次穿透，轻轻挤压使少量内容物溢出形成盲肠漏，将盲肠还纳入腹腔，连续缝合术关闭腹腔。对照组在开腹后仅暴露并翻动盲肠。各组术后皮下注射预热的生理盐水（37℃，5 mL/100 g）使动物复苏。模型制备前30 min，电针+NLRP3激活剂组腹腔注射100 mg/kg尼日利亚菌素钠盐，其他组给予等容量生理盐水。

  • 1.3 电针刺处理

  • 参照中国针灸学会实验针灸研究会制定的“动物针灸穴位图谱”，选取大鼠双侧肺俞穴和足三里穴，暴露针刺部位并消毒后，采用直径0.3 mm一次性无菌针灸针直刺进针后，接G6805-1A低频电子脉冲治疗仪进行疏密波电刺激（电流l~2 mA，频率2/15 Hz，波宽0.2~0.5 ms，以大鼠下肢出现轻微肌颤为合适），模型制备前5 d每天进行1次，模型制备结束时开始每6 h进行1次，30 min/次；非穴位电针组以相同参数针刺足三里及肺俞穴旁开0.5 cm非经非穴处。

  • 1.4 标本采集

  • 实验结束时安乐死大鼠，留取双肺组织，取左肺组织测定W/D比值，取右肺组织部分用4%多聚甲醛固定、部分经液氮速冻处理后于-80℃冰箱保存。

  • 1.5 肺组织湿重/干重（W/D）比值的测定

  • 取左肺上叶组织，PBS冲洗表面血渍后用滤纸吸干水渍，用精细天平称量湿重记为W，置于65℃恒温烘箱烘干48 h称重记为D，计算肺组织W/D比值。

  • 1.6 肺损伤评分

  • 取左肺上叶组织置于常规4%甲醛溶液固定、脱水、石蜡包埋、切片、HE染色，封片，在光学显微镜下观察病理学变化，并参照文献[6]的方法根据肺间质水肿、肺泡腔出血、炎性细胞浸润及纤维蛋白渗出4项进行肺损伤评分。

  • 1.7 ELISA法测定白细胞介素（IL）-1β、IL-18含量

  • 将部分左肺组织匀浆、4℃下1 200 r/min离心10 min，取上清液，严格按照IL-1β、IL-18 ELISA试剂盒说明书进行操作。

  • 1.8 Western blot法测定NLRP3、ASC、cleaved-caspase-1、GSDMD-N蛋白的表达

  • 将冻存肺组织冻融、离心、取蛋白，用BCA蛋白定量试剂盒测定蛋白浓度。取50 μg样品在12% SDS-PAGE凝胶上电泳后转膜，封闭2 h，TBST洗膜后分别加入NLRP3、ASC、cleaved-caspase-1、GSDMD-N一抗，4℃摇床孵育过夜后TBST洗膜3次，加入山羊抗兔抗体IgG二抗，室温孵育1 h，TBST洗膜后暗室显影曝光，采用Image J软件测量条带灰度值，以目的蛋白条带与β-actin内参蛋白条带灰度值的比值反映目的蛋白的表达水平。

  • 1.9 统计学方法

  • 数据采用SPSS22.0软件进行统计分析，正态分布的计量数据资料以x-±s表示，组间比较采用单因素方差分析，P＜0.05为差异有统计学意义。

  • 2 结果

  • 2.1 肺组织病理学变化

  • 光镜下观察，对照组大鼠肺组织未见明显病理学变化，模型组、电针组、电针+NLRP3激活剂组和非经非穴电针组可见不同程度肺泡及间质水肿、肺泡腔内炎性细胞浸润和出血；与模型组比较，电针组肺组织病理学损伤减轻，肺泡腔内出血减少，肺泡间隔轻微增厚；与电针组比较，电针+NLRP3激活剂组肺泡腔水肿渗出、炎性细胞浸润增加。模型组、电针组、电针+NLRP3激活剂组和非经非穴电针组肺损伤评分均高于对照组，电针组肺损伤评分低于模型组，电针+NLRP3激活剂组肺损伤评分高于电针组，差异有统计学意义（P＜0.05），见图1。

  • 图1 各组大鼠肺组织病理变化

  • 2.2 肺组织W/D比值的变化

  • 模型组、电针组、电针+NLRP3激活剂组和非经非穴电针组W/D比值均高于对照组，电针组W/D比值低于模型组，电针+NLRP3激活剂组W/D比值高于电针组，差异有统计学意义（P＜0.05），见表1。

  • 2.3 肺组织IL-1β、IL-18含量的变化

  • 模型组、电针组、电针+NLRP3激活剂组和非经非穴电针组IL-1β、IL-18含量均高于对照组，电针组IL-1β、IL-18含量均低于模型组，电针+NLRP3激活剂组IL-1β、IL-18含量均高于电针组，差异有统计学意义（P＜0.05），见表1。

  • 表1 5组大鼠W/D比值、IL-1β及IL-18含量比较

  • 注：a与对照组比较，P<0.05；b与模型组比较，P<0.05；c与电针组比较，P<0.05

  • 2.4 肺组织NLRP3、ASC、cleaved-caspase-1、GSDMD-N蛋白表达的变化

  • 模型组、电针组、电针+NLRP3激活剂组和非经非穴电针组NLRP3、ASC、cleaved-caspase-1、GSDMD-N蛋白表达均高于对照组，电针组NLRP3、ASC、cleaved-caspase-1、GSDMD-N蛋白表达均低于模型组，电针+NLRP3激活剂组NLRP3、ASC、cleaved-caspase-1、GSDMD-N蛋白表达均高于电针组，差异有统计学意义（P＜0.05），见图2。

  • 图2 各组大鼠肺组织NLRP3、ASC、cleaved-caspase-1、 GSDMD-N蛋白表达变化

  • 3 讨论

  • 脓毒症患者通常伴发多脏器功能损伤，甚至出现多脏器功能障碍，其中肺脏是脓毒症发病过程中最容易受到损伤的器官，它可能发展为急性肺损伤甚至急性呼吸窘迫综合征，并增加其它脏器功能障碍的风险[7]。本研究参照文献[5]的方法采用CLP制备脓毒症急性肺损伤模型，制模后大鼠肺组织损伤评分和W/D比值均升高，提示成功制备了大鼠脓毒症诱导的急性肺损伤模型。

  • 细胞焦亡是一种细胞炎症性坏死，它依赖于Gasdermin家族蛋白形成质膜孔隙，其形态特征包括胞核固缩或断裂、胞质肿胀、胞膜不完整且有炎性小体形成，细胞焦亡的主要标志是caspase和GSDM的激活以及大量促炎因子的释放[8]。当机体受到内源性或外源性危险信号刺激时，模式识别受体识别和形成胞内蛋白复合炎性小体。NLRP3是模式识别受体NLR家族的重要成员，包括NLRP3、ASC和caspase-1的NLRP3炎性小体裂解后激活caspase-1，从而启动依赖于caspase-1的经典细胞焦亡途径。活化的caspase-1会切割并分离GSDMD的N端，该N端结构域能在细胞膜上形成纳米孔，破坏细胞膜完整性，进而释放IL-1β、IL-18等细胞因子，引发细胞焦亡[9-10]。研究发现，NLRP3/caspase-1/GSDMD介导的经典焦亡信号通路在脓毒症的发生和发展中起着重要作用[11]，抑制NLRP3炎性小体介导的细胞焦亡能够减轻脓毒症急性肺损伤[12-13]。本研究中，制模后大鼠肺组织中NLRP3、ASC、cleaved-caspase-1和GSDMD-N蛋白的表达上调，IL-1β和IL-18的含量升高，提示脓毒症诱发了肺细胞焦亡。

  • 足三里穴是足阳明胃经的主要穴位之一，研究表明其具有抗炎和免疫调节的作用[14]。肺俞穴是足太阳膀胱经的重要穴位，常用于针灸治疗肺脏疾病。电针疗法是在针灸的基础上加入了低频率的脉冲电刺激以增加临床疗效的方法，针刺得气后，通过接近人体生物电的微电流与针灸相结合，有疏通经脉、促进循环、扶正祛邪、止痛止痉等作用。疏波、密波自动交替出现的疏密波为电针刺常用的调制脉冲波型，电针频率是影响效应的重要因素；研究表明，疏波2 Hz、密波15 Hz的疏密波电针刺激有抑制氧化应激、减轻炎症反应的作用，其刺激强度以动物的肢体出现轻微肌颤为合适[15-16]。据此，本研究参照文献[17]，使用疏波2 Hz、密波15 Hz电针刺激脓毒症大鼠的足三里和肺俞穴。研究结果显示，电针组相比于模型组和非经非穴电针组，具有降低肺损伤评分和W/D比值的效果；此外，电针组肺组织中NLRP3、ASC、cleaved-caspase-1和GSDMD-N蛋白表达下调，IL-1β和IL-18含量降低。与电针组相比，电针+NLRP3激活剂组的肺损伤评分、W/D比值、IL-1β含量和IL-18含量均升高，肺组织中NLRP3、ASC、cleaved-Caspase-1和GSDMD-N蛋白表达也上调。这些研究结果表明，电针刺激足三里穴和肺俞穴可能通过抑制肺细胞焦亡来减轻脓毒症诱发的急性肺损伤。同时，给予NLRP3激活剂可以部分逆转电针刺对脓毒症急性肺损伤的保护作用，这提示电针刺激足三里穴和肺俞穴可能通过抑制NLRP3介导的、caspase-1依赖的经典细胞焦亡途径来减轻脓毒症诱发的大鼠急性肺损伤。

  • 综上所述，电针刺足三里穴和肺俞穴减轻脓毒症急性肺损伤的机制可能与抑制NLRP3/caspase-1/GSDMD介导的经典细胞焦亡信号通路的过度激活有关。

  • 参考文献

    • [1] Beitler JR,Thompson BT,Baron RM,et al.Advancing precision medicine for acute respiratory distress syndrome[J].Lancet Respir Med,2022,10(1):107-120.

    • [2] Auriemma CL,Zhuo HJ,Delucchi K,et al.Acute respiratory distress syndrome-attributable mortality in critically ill patients with sepsis[J].Intensive Care Med,2020,46(6):1222-1231.

    • [3] 宫丽荣,史佳,张圆,等.α7nAChR在电针减轻大鼠内毒素性急性肺损伤中的作用:与JAK2/STAT3信号通路的关系[J].中华麻醉学杂志,2018,38(6):739-742.

    • [4] Wang J,Li JR,Lou AN,et al.Sacubitril/valsartan alleviates sepsis-induced acute lung injury via inhibiting GSDMD-dependent macrophage pyroptosis in mice[J].FEBS J,2023,290(8):2180-2198.

    • [5] Wang FQ,Chen M,Wang CC,et al.Single-cell sequencing reveals the regulatory role of Maresin1 on neutrophils during septic lung injury[J].Cells,2022,11(23):3733.

    • [6] Li H,Qiu D,Yang H,et al.Therapeutic efficacy of excretory-secretory products of Trichinella spiralis adult worms on Sepsis-induced acute lung injury in a mouse model[J].Front Cell Infect Microbiol,2021,11:653843.

    • [7] Niederman MS,Baron RM,Bouadma L,et al.Initial antimicrobial management of sepsis[J].Crit Care,2021,25(1):307.

    • [8] Galluzzi L,Vitale I,Aaronson SA,et al.Molecular mechanisms of cell death:recommendations of the Nomenclature Committee on Cell Death 2018[J].Cell Death Differ,2018,25(3):486-541.

    • [9] Zheng X,Wan J,Tan G.The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in diabetic retinopathy[J].Front Immunol,2023,14:1151185.

    • [10] Guo J,Luo Y,Zuo J,et al.Echinacea polyphenols inhibit NLRP3-dependent pyroptosis,apoptosis,and necroptosis via suppressing NO production during lipopolysaccharide-induced acute lung injury[J].J Agric Food Chem,2023,71(19):7289-7298.

    • [11] Han Z,Ma J,Han Y,et al.Irisin attenuates acute lung injury by suppressing the pyroptosis of alveolar macrophages[J].Int J Mol Med,2023,51(4):32.

    • [12] Liu Y,Zhou J,Luo Y,et al.Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo[J].Chin Med,2021,16(1):127.

    • [13] Zeng YJ,Qin QW,Li KY,et al.PKR suppress NLRP3-pyroptosis pathway in lipopolysaccharide-induced acute lung injury model of mice[J].Biochem Biophys Res Commun,2019,519(1):8-14.

    • [14] Jiang HC,Shang Z,You LP,et al.Electroacupuncture pretreatment at Zusanli(ST36)ameliorates hepatic ischemia/reperfusion injury in mice by reducing oxidative stress via activating vagus nerve-dependent Nrf2 pathway[J].J Inflamm Res,2023,16:1595-1610.

    • [15] Dong SA,Gong LR,Yu JB,et al.The role of melatonin in electroacupuncture alleviating lung injury induced by limb ischemia-reperfusion in rabbits[J].Med Sci Monit,2020,26:e922525.

    • [16] Gong LR,Kan YX,Lian Y,et al.Electroacupuncture attenuates limb ischemia-reperfusion-induced lung injury via p38 mitogen-activated protein kinase-nuclear factor erythroid-2-related factor-2/heme oxygenase pathway[J].J Surg Res,2020,246:170-181.

    • [17] 宫丽荣,董树安,阚永星,等.α7烟碱型乙酰胆碱受体在电针减轻肢体缺血再灌注兔肺损伤中的作用[J].中国中西医结合外科杂志,2019,25(4):443-447.

图1 各组大鼠肺组织病理变化

表1 5组大鼠W/D比值、IL-1β及IL-18含量比较

图2 各组大鼠肺组织NLRP3、ASC、cleaved-caspase-1、 GSDMD-N蛋白表达变化

图表 1/1

  • 基本信息

    中图分类号: R655.3；R245.31
    文献标识码: A
    DOI: 10.3969/j.issn.1007-6948.2023.06.017

    基金信息

    国家自然科学基金青年项目（82004076）；

    稿件历史

    收稿日期: 2023-06-03

  • 参考文献

    • [1] Beitler JR,Thompson BT,Baron RM,et al.Advancing precision medicine for acute respiratory distress syndrome[J].Lancet Respir Med,2022,10(1):107-120.

    • [2] Auriemma CL,Zhuo HJ,Delucchi K,et al.Acute respiratory distress syndrome-attributable mortality in critically ill patients with sepsis[J].Intensive Care Med,2020,46(6):1222-1231.

    • [3] 宫丽荣,史佳,张圆,等.α7nAChR在电针减轻大鼠内毒素性急性肺损伤中的作用:与JAK2/STAT3信号通路的关系[J].中华麻醉学杂志,2018,38(6):739-742.

    • [4] Wang J,Li JR,Lou AN,et al.Sacubitril/valsartan alleviates sepsis-induced acute lung injury via inhibiting GSDMD-dependent macrophage pyroptosis in mice[J].FEBS J,2023,290(8):2180-2198.

    • [5] Wang FQ,Chen M,Wang CC,et al.Single-cell sequencing reveals the regulatory role of Maresin1 on neutrophils during septic lung injury[J].Cells,2022,11(23):3733.

    • [6] Li H,Qiu D,Yang H,et al.Therapeutic efficacy of excretory-secretory products of Trichinella spiralis adult worms on Sepsis-induced acute lung injury in a mouse model[J].Front Cell Infect Microbiol,2021,11:653843.

    • [7] Niederman MS,Baron RM,Bouadma L,et al.Initial antimicrobial management of sepsis[J].Crit Care,2021,25(1):307.

    • [8] Galluzzi L,Vitale I,Aaronson SA,et al.Molecular mechanisms of cell death:recommendations of the Nomenclature Committee on Cell Death 2018[J].Cell Death Differ,2018,25(3):486-541.

    • [9] Zheng X,Wan J,Tan G.The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in diabetic retinopathy[J].Front Immunol,2023,14:1151185.

    • [10] Guo J,Luo Y,Zuo J,et al.Echinacea polyphenols inhibit NLRP3-dependent pyroptosis,apoptosis,and necroptosis via suppressing NO production during lipopolysaccharide-induced acute lung injury[J].J Agric Food Chem,2023,71(19):7289-7298.

    • [11] Han Z,Ma J,Han Y,et al.Irisin attenuates acute lung injury by suppressing the pyroptosis of alveolar macrophages[J].Int J Mol Med,2023,51(4):32.

    • [12] Liu Y,Zhou J,Luo Y,et al.Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo[J].Chin Med,2021,16(1):127.

    • [13] Zeng YJ,Qin QW,Li KY,et al.PKR suppress NLRP3-pyroptosis pathway in lipopolysaccharide-induced acute lung injury model of mice[J].Biochem Biophys Res Commun,2019,519(1):8-14.

    • [14] Jiang HC,Shang Z,You LP,et al.Electroacupuncture pretreatment at Zusanli(ST36)ameliorates hepatic ischemia/reperfusion injury in mice by reducing oxidative stress via activating vagus nerve-dependent Nrf2 pathway[J].J Inflamm Res,2023,16:1595-1610.

    • [15] Dong SA,Gong LR,Yu JB,et al.The role of melatonin in electroacupuncture alleviating lung injury induced by limb ischemia-reperfusion in rabbits[J].Med Sci Monit,2020,26:e922525.

    • [16] Gong LR,Kan YX,Lian Y,et al.Electroacupuncture attenuates limb ischemia-reperfusion-induced lung injury via p38 mitogen-activated protein kinase-nuclear factor erythroid-2-related factor-2/heme oxygenase pathway[J].J Surg Res,2020,246:170-181.

    • [17] 宫丽荣,董树安,阚永星,等.α7烟碱型乙酰胆碱受体在电针减轻肢体缺血再灌注兔肺损伤中的作用[J].中国中西医结合外科杂志,2019,25(4):443-447.


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