hjbm Hans Journal of Biomedicine 2161-8976 2161-8984 beplay体育官网网页版等您来挑战！ 10.12677/hjbm.2025.151009 hjbm-104796 Articles 医药卫生 藿香正气液对脂多糖致小鼠急性肺损伤的 保护作用
Protective Effect of Huoxiangzhengqi Liquid on Lipopolysaccharide-Induced Acute Lung Injury in Mice
邓 悦 1 段鑫昊 1 蒋学君 1 张 军 2 高 敏 1 苏俊豪 1 邹 镇 2 陈承志 1 邱景富 1 张弘扬 1 重庆医科大学公共卫生学院，重庆 重庆医科大学检验医学院，重庆 06 12 2024 15 01 82 92 10 10 ：2024 2 10 ：2024 2 1 ：2025 Copyright © 2024 beplay安卓登录 All rights reserved. 2024 This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/ 目的：探讨藿香正气液(HXZQ)对脂多糖(LPS)引起的急性肺损伤(ALI)的保护作用及其分子机制。方法：HXZQ灌胃7 d后，采用腹腔注射LPS24 h建立ALI动物模型，观察HXZQ对LPS诱导的ALI的保护作用。结果：HXZQ显著降低中性粒细胞浸润，表现为中性粒细胞活性标志物髓过氧化物酶(MPO)的降低；HXZQ还能抑制巨噬细胞介导的炎症，具体表现为巨噬细胞标志物CD68和促炎因子Il-6、Il-1β的降低；同时，HXZQ通过降低淋巴细胞介导的炎症发挥免疫调节作用，具体表现为细胞因子Il-17a和Gm-csf的降低。结论：HXZQ可以通过抑制免疫细胞的浸润及其分泌的炎症细胞因子来拮抗LPS诱导的ALI。我们的研究强调了HXZQ的免疫调节作用，并提示HXZQ可能是治疗ALI的新药物。
Objective: To investigate the protective effect of Huoxiangzhengqi Liquid (HXZQ) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its molecular mechanism. Methods: After 7d of HXZQ gavage, an animal model of ALI was established by intraperitoneal injection of LPS for 24 h to observe the protective effect of HXZQ on LPS-induced ALI. Results: HXZQ significantly reduced neutrophil infiltration, as evidenced by the reduction of myeloperoxidase (MPO), a marker of neutrophil activity; HXZQ also inhibited macrophage-mediated inflammation, as evidenced by the reduction of the macrophage marker CD68 and the pro-inflammatory factors Il-6 and Il-1β; at the same time, HXZQ played an immunomodulatory role by decreasing lymphocyte-mediated inflammation. This was specifically manifested by the reduction of cytokines Il-17a and Gm-csf. Conclusion: HXZQ can antagonize LPS-induced ALI by inhibiting the infiltration of immune cells and their secretion of inflammatory cytokines. Our study highlights the immunomodulatory effects of HXZQ and suggests that HXZQ may be a new drug for the treatment of ALI.
藿香正气液，脂多糖，急性肺损伤，炎症反应
Huoxiangzhengqi Liquid
Lipopolysaccharide Acute Lung Injury Inflammation 1. 引言

急性肺损伤(Acute lung injury, ALI)/急性呼吸窘迫综合征(Acute respiratory distress syndrome, ARDS)是一种以肺部炎症为主要病因的疾病，其症状包括呼吸困难和呼吸短促，严重时可危及生命 [1] 。腹腔注射脂多糖(Lipopolysaccharide, LPS)致小鼠脓毒症是建立ALI模型的经典方法 [2] [3] ，而脓毒症诱发ALI的发病机制与多形核中性粒细胞的积累和活化、氧自由基的释放、炎症细胞的活化有关 [4] [5] 。LPS是革兰氏阴性细菌内毒素的主要糖脂成分，可引起多器官损伤包括胃肠道、脑、肾和肝脏损伤 [6] - [10] ，也是诱导ALI动物模型最常用的激活剂 [2] ，它通过改变肺泡毛细血管通透性，从而引起肺水肿 [11] 。大量研究表明，抑制炎症反应可减轻LPS诱导的ALI [12] 。

传统中药处方由数百种不同的草药植物或含有复杂化学成分的提取物组成，数千年来一直用于治疗人类疾病 [13] 。藿香正气液(Huoxiangzhengqi liquid, HXZQ)是一种中草药配方，最早记载于宋代典籍中，由藿香、阿蜜、木兰皮、槟榔皮等数十种中草药组成 [14] ，是2015年版《中国药典》收录的非处方药之一 [15] 。HXZQ最初主要用于治疗感冒、呕吐和腹泻 [16] ，其主要成分具有抗炎、抗菌、抗氧化、抗血小板凝血和神经保护作用 [17] - [19] 。最近的一项研究表明，HXZQ在治疗胃肠道感冒方面比西药更有效，并且具有更好的安全性 [20] ；另一项研究则也有研究发现证实了HXZQ对痢疾杆菌和鼠伤寒沙门菌引起的腹泻小鼠肠道黏膜免疫具有促进作用 [21] 。一项随机对照试验显示，HXZQ在改善COVID-19患者临床症状方面可能具有临床优势 [22] 。然而，HXZQ对ALI的影响尚不清楚。在这项研究中，我们的目的是确定HXZQ是否对LPS诱导的ALI有保护作用，并阐明其潜在机制。

 2. 材料和方法 2.1 药品及主要试剂

脂多糖(来源于大肠杆菌O111：B4)购于美国Sigma公司。藿香正气液购于太极集团重庆涪陵药厂有限公司。苏木精–伊红染色试剂购于北京索拉生物科技有限公司。兔β-肌动蛋白抗体购于美国ABclonal公司。兔抗CD68抗体购于中国武汉Proteintech公司。兔抗MPO抗体购于英国Abcam公司。BCA蛋白检测试剂盒购于中国上海天宇生物科技有限公司。DAB试剂购于中国北京中山金桥生物科技有限公司。山羊血清、生物素化山羊抗兔IgG购于中国武汉博斯特生物技术公司。ECL化学发光超敏显色试剂盒、TRizol试剂购于中国南京凯基生物技术有限公司。RIPA裂解缓冲液购于上海碧云天生物技术有限公司。

 2.2 动物分组与给药

SPF级7周龄健康雄性C57BL/6J小鼠40只(18-22 g)，购于重庆医科大学实验动物中心。所有动物饲养在稳定的标准条件下：温度：23℃ ± 1℃，湿度：55% ± 10%，光/暗循环12/12 h，允许自由摄食和饮水。适应性喂养1周后，随机分为4组，每组10只。对照组和LPS组小鼠口服0.9%无菌生理盐水。HXZQ组和HXZQ-LPS组小鼠灌胃HXZQ液(1.3 mg/kg)，连续7 d。LPS组和HXZQ-LPS组小鼠在灌胃的最后一天腹腔注射LPS (6 mg/kg)。实验设计如 图1A 所示。所有动物实验均获得重庆医科大学伦理委员会的审查批准，并采取了一切措施来减少动物的痛苦。

 <xref></xref>2.3 苏木精–伊红染色(Hematoxylin-Eosin Staining, H&E)

参考文献 [23] 中的方法进行H&E染色。解剖组织用4%多聚甲醛固定，石蜡包埋。石蜡切片在65℃烤箱中烘烤1 h，然后用二甲苯脱蜡，再用梯度乙醇(100%、95%、85%、75%)水合。最后用苏木精和伊红染色对切片染色。染色结束后，切片梯度乙醇(75%、85%、95%、100%)后，用二甲苯透明，中性树脂密封切片。24 h后光学显微镜观察染色组织切片。

 2.4. 免疫组化检测(Immunohistochemistry, IHC)

参考文献 [24] 中的方法进行免疫组织化学检测。肺组织切片在65℃的烤箱中烘烤1 h以上，然后用60℃的二甲苯Ⅰ、Ⅱ各脱蜡30 min，再用梯度乙醇(100%、95%、85%、75%)水化3 min，流水冲洗10 min，蒸馏水泡10 min。将切片置于微波炉中微沸的柠檬酸盐缓冲液进行抗原热修复15 min，取出后冷却至室温。用3%过氧化氢去离子水孵育10 min抑制组织切片内源性过氧化物，PBS洗涤后加入山羊血清封闭30 min，再加入CD68抗体(1:200) 4℃孵育过夜。次日，取切片与生物素化山羊抗兔IgG孵育15 min，PBS洗涤。加入DAB溶液室温孵育5 min显色后，再将切片用苏木精核染，后经乙醇梯度(75%、85%、95%、100%)脱水，二甲苯透明等过程，最后用中性树脂密封切片，并在光学显微镜下观察。

 2.5. 组织RNA提取及定量聚合酶链式反应

参考文献 [25] 中的方法进行定量聚合酶链式反应(Quantitative polymerase chain reaction, qPCR)。使用TRizol试剂从肺组织中提取总RNA。使用5X PrimeScript™RT Master Mix进行逆转录。采用Blast TaqTM2X Qpcr Master Mix试剂盒和基因特异性引物扩增cDNA，并通过Bio-Rad CFX Manager 3.1进行qPCR反应。所有特异性引物基因都是由中国上海生物工程有限公司设计的。反应体系：TB Green 5 μL、10 μM上游引物0.25 μL、10 μM下游引物0.25 μL、cDNA1 μL、DEPC水3.5 μL。qPCR反应条件“见 表1 ”，目的基因引物序列“见 表2 ”。

<xref></xref>Table 1. qPCR reaction conditionsTable 1. qPCR reaction conditions 表1. qPCR反应条件

Steps

Temperature (˚C)

Times

1

预变性

95

3 min

2

变性

95

15 s

3

退火温度

60

1 min

4

循环

Go to Step 2

40 Cycles

5

延伸

65

0.5˚C per 5s

6

保存

4

∞
<xref></xref>Table 2. Primer sequences of target genesTable 2. Primer sequences of target genes 表2. 目的基因引物序列

Gene

Forward (5' → 3')

Reverse (5' → 3')

β-Actin

GTGACGTTGACATCCGTAAAGA

GCCGGACTCATCGTACTCC

Il-6

CTGCAAGAGACTTCCATCCAG

AGTGGTATAGACAGGTCTGTTGG

Il-1β

GAAATGCCACCTTTTGACAGTG

TGGATGCTCTCATCAGGACAG

Il-17a

TCAGCGTGTCCAAACACTGAG

CGCCAAGGGAGTTAAAGACTT

Gm-csf

GGCCTTGGAAGCATGTAGAGG

GGAGAACTCGTTAGAGACGACTT

Il-13

GGGATACCCACCGTTTAACCA

AGGTTTACTCTCCGAAAGCTCTT

Il-22

ATGAGTTTTTCCCTTATGGGGAC

GCTGGAAGTTGGACACCTCAA
2.6. Western Blot分析

参考文献 [26] 中的方法进行Western blot分析。使用RIPA裂解缓冲液从肺组织中提取总蛋白，并用BCA试剂盒测定总蛋白浓度。变性蛋白(100 ˚C, 10 min)后，将样品加入8% SDS-PAGE凝胶中进行电泳，电泳结束后将分离的蛋白转移到PVDF膜上。随后，将条带用5%脱脂奶粉封闭1.5 h后，再用一抗(MPO, 1:3000)在4℃下孵育过夜。次日，用稀释后的二抗孵育条带1 h，再加入ECL化学发光试剂进行显色，并用分子成像凝胶Doc XR系统对印迹进行可视化。最后，以β-actin为内参使用Image J软件对显色条带进行灰度值定量分析。

 2.7. 统计分析

本实验所有数据均以均数 ± 均数标准误差(S.E.M.)表示。采用GraphPad Prism 8.0软件，采用独立t检验、非参数Mann-Whitney U检验、单因素或重复方差分析(ANOVA)等统计分析方法。P < 0.05为差异有统计学意义。

 3. 结果 3.1. HXZQ可拮抗LPS诱导的肺损伤

为探讨HXZQ对LPS诱导的ALI的保护作用，采用H&E染色观察肺组织病理变化。如 图1B 所示，LPS引起肺组织间质壁明显增厚，肺组织炎症细胞明显浸润。此外，与对照组相比LPS显著提高了

Figure 1. Effect of Huoxiangzhengqi Liquid (HXZQ) on histopathological changes in the lung tissues of mice-treated with LPS. A. The experimental design of this study. B. Representative histological change in the lungs of different groups of mice were observed in H&E staining. C. Lung injury score. Data were presented as mean ± S.E.M. Statistical analysis was performed by using repeated-measure ANOVA or independent student t test or Mann–Whitney U test. D. Cell count of BALF. Data were presented as mean ± S.E.M. Statistical analysis was performed by using repeated-measure ANOVA or independent student t test or Mann-Whitney U test--图1. HXZQ对LPS处理小鼠肺组织病理变化的影响。A. 本研究的实验设计流程图。B. H&E染色观察不同组小鼠肺部具有代表性的组织学变化。C. 肺损伤评分。数据以均数 ± S.E.M表示。采用重复测量方差分析或独立t检验或Mann-Whitney U检验进行统计分析。D. BALF的细胞计数。数据以均数 ± S.E.M表示。采用重复测量方差分析或独立t检验或Mann-Whitney U检验进行统计分析--

肺损伤评分，而HXZQ明显改善了LPS处理小鼠的肺组织病理学，并降低了肺损伤的组织学评分( 图1B & 图1C )。小鼠处死后收集支气管肺泡灌洗液(Bronchoalveolar lavage fluid, BALF)，并立即用自动细胞计数仪进行细胞计数。结果明确显示LPS组细胞数量显著增加，HXZQ显著减少细胞数量( 图1D )。这些数据均表明HXZQ对LPS诱导的ALI小鼠有保护作用。

 3.2. HXZQ抑制LPS诱导的MPO活性

髓过氧化物酶(Myeloperoxidase, MPO)在中性粒细胞和单核细胞中表达，MPO水平升高与炎症和氧化应激增加有关 [27] 。我们用Western blot验证LPS处理后MPO的变化，结果显示LPS处理后小鼠肺组织中MPO的表达增加，而HXZQ则显著降低MPO的表达( 图2 )，提示HXZQ能有效抑制肺组织中性粒细胞的浸润。

Figure 2. Effect of HXZQ on MPO expression in the lung tissues of mice-treated with LPS. Data were presented as mean ± S.E.M. Statistical analysis was performed by using repeated-measure ANOVA or independent student t test or Mann-Whitney U test--图2. HXZQ对LPS处理小鼠肺组织MPO蛋白表达的影响。数据以均数 ± S.E.M表示。统计分析采用重复测量方差分析、独立t检验或Mann-Whitney U检验-- 3.3. HXZQ减轻LPS处理小鼠肺组织巨噬细胞介导的炎症反应

CD68是巨噬细胞的标志物 [28] 。为评价LPS对肺组织的炎症作用，我们采用IHC检测CD68水平。IHC结果显示，LPS上调了CD68的表达，而HXZQ进一步显著降低了CD68的表达( 图3A )。促炎因子在LPS诱导的炎症反应中起着至关重要的作用，而在众多炎症因子中Il-6和Il-1β是参与LPS反应的关键细胞因子 [29] [30] 。因此，我们采用qPCR法检测Il-6和Il-1β的表达量，结果显示LPS组Il-6和Il-1β的表达急剧升高，HXZQ有效降低了这些炎症细胞因子的水平( 图3B & 图3C )。综上所述，HXZQ调节LPS诱导的巨噬细胞浸润及相关促炎因子的分泌。

 3.4. HXZQ重塑LPS刺激引起的炎症

先天淋巴样细胞(Innate lymphoid cells, ILCs)是一类具有淋巴细胞表型的天然免疫细胞，分为ILC1、ILC2和ILC3亚群 [31] 。就像其他淋巴细胞一样，ILCs可以产生各种细胞因子。例如，ILCs2可以分泌Gm-csf和Il-13，而ILCs3可以分泌Il-17a、Il-22 [32] [33] 。因此，ILCs在宿主防御和急性炎症中起着至关重要的作用 [34] 。为了探讨ILCs在急性肺损伤中的作用，我们采用qPCR方法检测小鼠肺组织中相关基因的表达。LPS组II型和III型ILCs相关炎症因子Il-17a、Gm-csf、Il-13和Il-22的表达量显著升高，而HXZQ不仅呈现出抑制Il-13和Il-22表达的趋势，更进一步显著降低了Il-17a和Gm-csf的表达量( 图4 )，表明HXZQ降低了炎症因子的分泌重塑了LPS诱导的免疫谱。

Figure 3. The effect of HXZQ on the content of inflammatory factors in the lung tissues of mice treated with LPS. (A) The CD68 expression was determined by immunohistochemical and the representative images were shown. (B) (C) Effect of HXZQ on the expression of (B) Il-6 and (C) Il-1β mRNA in the lung tissue of mice-treated with LPS. Data were presented as mean ± S.E.M. Statistical analysis was performed by using repeated-measure ANOVA or independent student t test or Mann–Whitney U test--图3. HXZQ对LPS处理小鼠肺组织炎症因子含量的影响。(A) 用免疫组化法测定CD68的表达，并显示其代表性图像。(B) (C) HXZQ对LPS处理的小鼠肺组织中(B) Il-6 和(C) Il-1β mRNA表达的影响。数据以均数 ± S.E.M表示。统计分析采用重复测量方差分析或独立t检验或Mann-Whitney U检验-- Figure 4. Expression of intrinsic lymphocyte factors was determined by qPCR. Effects of HXZQ on the mRNA expressions of (A) Il-17a, (B) Gm-csf, (C) Il-13 and (D) Il-22 in the lung tissues of mice treated with LPS. Data were presented as mean ± S.E.M. Statistical analysis was performed by using repeated-measure ANOVA or independent student t test or Mann-Whitney U test.--图4. qPCR检测淋巴细胞内炎症因子的表达。HXZQ对LPS治疗小鼠肺组织中(A) Il-17a、(B) Gm-csf、(C) Il-13和(D) Il-22 mRNA表达的影响。数据以均数 ± S.E.M表示。统计分析采用重复测量方差分析、独立t检验或Mann-Whitney U检验-- 4. 讨论

中医是中国悠久历史文化的瑰宝，而HXZQ是著名的中药配方之一。目前，越来越多的证据显示HXZQ对胃肠道疾病的症状缓解作用 [14] 。因HXZQ的配方具有抑制炎症、调节胃肠功能和免疫保护等多种药理功能，其有效成分类型和结构多样，能够有效降低其耐药性 [35] 。另外，中药方剂成分复杂，各种成分相辅相成，对多种疾病都具有良好的治疗效果。结合近期HXZQ抗新冠肺炎效果的研究，相信中草药方剂一定可以在减轻肺部炎症方面发挥更大的作用 [13] [22] 。

急性呼吸道感染可对肺组织造成严重损害，目前缺乏有效的临床治疗方法和药物 [36] [37] 。因此，对ALI发病机制的研究和有效药物的探寻就显得尤为重要。幸运的是，我们发现HXZQ通过重塑免疫图谱的方式，有效地减轻了LPS诱导的肺组织病理损伤。MPO是LPS处理中一个关键的炎症酶 [38] [39] 。在本研究中，我们证实了HXZQ干预降低了LPS处理小鼠肺组织中MPO的含量，提示了HXZQ的抗炎作用。在炎症组织、肿瘤组织和其他免疫组织病理学应用中，CD68被认为是单核/巨噬细胞免疫染色的有价值的细胞化学标记物 [40] 。IHC结果表明LPS导致CD68水平升高，而HXZQ能有效降低CD68水平。另外，在LPS处理的小鼠肺组织中检测到巨噬细胞分泌的促炎细胞因子Il-6和Il-1β水平升高，而HXZQ显著降低了这两个因子的表达水平。综上所述，我们的数据证明了HXZQ可以有效地减轻LPS引起的肺部炎症。

ILCs是最近发现的一群淋巴细胞，在保护组织免受病原体侵害、恢复组织完整性和肿瘤免疫监视中发挥重要作用 [41] 。此外，ILCs还在各种黏膜组织中(如肺部)介导保护性免疫 [42] 。一项研究使用LPS刺激体外全血，检测到ILCs相关细胞因子水平升高 [43] 。在本研究中，qPCR结果表明LPS导致Gm-csf、Il-17a等ILCs相关因子mRNA表达升高，而HXZQ干预后其表达量降低，证实了HXZQ通过影响淋巴细胞内在相关因子的分泌达到免疫促进作用。

目前，中药配方中有效成分的作用机理是研究的热点。甘草提取物对抑制巨噬细胞的炎症反应，提高细胞存活率具有重要作用 [44] 。同时，黄芩苷对脂多糖诱导的炎症反应有明显的抑制作用 [45] 。因此，对HXZQ有效成分的分析及其抗病机制的研究将是这项工作未来的重要组成部分。总之，我们的研究表明HXZQ对ALI具有抗炎作用。结合近期HXZQ和COVID-19相关研究 [22] ，我们认为HXZQ和肺部疾病将是未来值得探索的领域之一。

 基金项目

国家资助博士后研究人员计划(GZC20233340)；重庆市博士后研究项目特别资助(2023CQBSHTB3082)。

 竞争利益声明

作者声明无利益冲突。

 伦理批准

本工作已获得重庆医科大学伦理委员会批准。

 数据和材料的可用性

本研究中使用和/或分析的数据集可应通讯作者的合理要求向其提供。

 NOTES

*共一作者。

#通讯作者。

 References Fan, E., Brodie, D. and Slutsky, A.S. (2018) Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment. JAMA, 319, 698-710. >https://doi.org/10.1001/jama.2017.21907 de Souza Xavier Costa, N., Ribeiro Júnior, G., dos Santos Alemany, A.A., Belotti, L., Zati, D.H., Frota Cavalcante, M., et al. (2017) Early and Late Pulmonary Effects of Nebulized LPS in Mice: An Acute Lung Injury Model. PLOS ONE, 12, e0185474. >https://doi.org/10.1371/journal.pone.0185474 Fujita, M., Kuwano, K., Kunitake, R., Hagimoto, N., Miyazaki, H., Kaneko, Y., et al. (1998) Endothelial Cell Apoptosis in Lipopolysaccharide-Induced Lung Injury in Mice. International Archives of Allergy and Immunology, 117, 202-208. >https://doi.org/10.1159/000024011 Huang, X.L., Ma, H.J., Zhou, X.H., Fan, Y.M., Xian, X.H. and Cao, H. (2010) Effect of Exogenous Hydrogen Sulfide on Polymorphonuclear Neutrophil Accumulation in Acute Lung Injury Rat Induced by Lipopolysaccharides and Its Mechanism. Chinese Journal of Applied Physiology, 26, 477-480. Liaudet, L., Rosenblatt-Velin, N. and Pacher, P. (2013) Role of Peroxynitrite in the Cardiovascular Dysfunction of Septic Shock. Current Vascular Pharmacology, 11, 196-207. >https://doi.org/10.2174/1570161111311020009 Kemp, M.W., Saito, M., Nitsos, I., Jobe, A.H., Kallapur, S.G. and Newnham, J.P. (2011) Exposure to in Utero Lipopolysaccharide Induces Inflammation in the Fetal Ovine Skin. Reproductive Sciences, 18, 88-98. >https://doi.org/10.1177/1933719110380470 Wolfs, T.G.A.M., Buurman, W.A., Zoer, B., Moonen, R.M.J., Derikx, J.P.M., Thuijls, G., et al. (2009) Endotoxin Induced Chorioamnionitis Prevents Intestinal Development during Gestation in Fetal Sheep. PLOS ONE, 4, e5837. >https://doi.org/10.1371/journal.pone.0005837 Nitsos, I., Rees, S.M., Duncan, J., Kramer, B.W., Harding, R., Newnham, J.P., et al. (2006) Chronic Exposure to Intra-Amniotic Lipopolysaccharide Affects the Ovine Fetal Brain. Journal of the Society for Gynecologic Investigation, 13, 239-247. >https://doi.org/10.1016/j.jsgi.2006.02.011 Ding, Y., Liu, P., Chen, Z., Zhang, S., Wang, Y., Cai, X., et al. (2018) Emodin Attenuates Lipopolysaccharide-Induced Acute Liver Injury via Inhibiting the TLR4 Signaling Pathway in Vitro and in Vivo. Frontiers in Pharmacology, 9, Article No. 962. >https://doi.org/10.3389/fphar.2018.00962 Huang, W., Lan, X., Li, X., Wang, D., Sun, Y., Wang, Q., et al. (2017) RETRACTED: Long Non-Coding RNA PVT1 Promote LPS-Induced Septic Acute Kidney Injury by Regulating TNFα and JNK/NF-κB Pathways in HK-2 Cells. International Immunopharmacology, 47, 134-140. >https://doi.org/10.1016/j.intimp.2017.03.030 Fisher, A.B., Dodia, C., Chatterjee, S. and Feinstein, S.I. (2019) A Peptide Inhibitor of NADPH Oxidase (NOX2) Activation Markedly Decreases Mouse Lung Injury and Mortality Following Administration of Lipopolysaccharide (LPS). International Journal of Molecular Sciences, 20, Article No. 2395. >https://doi.org/10.3390/ijms20102395 Jiang, W., Luo, F., Lu, Q., Liu, J., Li, P., Wang, X., et al. (2016) The Protective Effect of Trillin LPS-Induced Acute Lung Injury by the Regulations of Inflammation and Oxidative State. Chemico-Biological Interactions, 243, 127-134. >https://doi.org/10.1016/j.cbi.2015.09.010 Zhou, P. (2010) Hot Topic: Editorial [Traditional Chinese Medicine] (Ping Zhou). Combinatorial Chemistry&High Throughput Screening, 13, 836. >https://doi.org/10.2174/138620710793360329 Xie, Y.C. and Tang, F. (2004) Experimental Study on Protecting Intestinal Barrier Function of Huoxiang Zhengqi Soft Capsule. China Journal of Chinese Materia Medica, 29, 456-458. Read, B.E. (1930) The Chinese Pharmacopoeia. The Canadian Medical Association Journal, 23, 568-570. Li, K., Yuan, J. and Su, W. (2006) Determination of Liquiritin, Naringin, Hesperidin, Thymol, Imperatorin, Honokiol, Isoimperatorin, and Magnolol in the Traditional Chinese Medicinal Preparation Huoxiang-Zhengqi Liquid Using High-Performance Liquid Chromatography. Yakugaku Zasshi, 126, 1185-1190. >https://doi.org/10.1248/yakushi.126.1185 Ramalingam, M., Kim, H., Lee, Y. and Lee, Y. (2018) Phytochemical and Pharmacological Role of Liquiritigenin and Isoliquiritigenin from Radix Glycyrrhizae in Human Health and Disease Models. Frontiers in Aging Neuroscience, 10, Article No. 348. >https://doi.org/10.3389/fnagi.2018.00348 Ye, L., Gho, W.M., Chan, F.L., Chen, S. and Leung, L.K. (2008) Dietary Administration of the Licorice Flavonoid Isoliquiritigenin Deters the Growth of MCF‐7 Cells Overexpressing Aromatase. International Journal of Cancer, 124, 1028-1036. >https://doi.org/10.1002/ijc.24046 Zhu, X., Liu, J., Huang, S., Zhu, W., Wang, Y., Chen, O., et al. (2019) Neuroprotective Effects of Isoliquiritigenin against Cognitive Impairment via Suppression of Synaptic Dysfunction, Neuronal Injury, and Neuroinflammation in Rats with Kainic Acid-Induced Seizures. International Immunopharmacology, 72, 358-366. >https://doi.org/10.1016/j.intimp.2019.04.028 Zhao, H.J., Guo, L.P., Yang, F.W., Zhang, M.Y., Zhang, L.S., Liu, Z., Li, Y., Ji, Z.C., Zhang, J.H. and Zheng, W.K. (2017) Huoxiang Zhengqi Formulas for Treatment of Gastrointestinal Type Cold: A Systematic Review and Meta-Analysis. China Journal of Chinese Materia Medica, 42, 1495-1499. He, Y. (2006) Effects of Huoxiangzhengqi Liquid on Enteric Mucosal Immune Responses in Mice with Bacillus Dysenteriae and Salmonella Typhimurium Induced Diarrhea. World Journal of Gastroenterology, 12, 7346-7349. >https://doi.org/10.3748/wjg.v12.i45.7346 Yan, B., Jiang, Z., Yuan, J., Li, M., Zeng, J., Tang, J., et al. (2021) Effects and Safety of Herbal Medicines among Community-Dwelling Residents during COVID-19 Pandemic: A Large Prospective, Randomized Controlled Trial (RCT). Phytomedicine, 85, Article ID: 153403. >https://doi.org/10.1016/j.phymed.2020.153403 Zhang, S., Jiang, X., Cheng, S., Fan, J., Qin, X., Wang, T., et al. (2020) Titanium Dioxide Nanoparticles via Oral Exposure Leads to Adverse Disturbance of Gut Microecology and Locomotor Activity in Adult Mice. Archives of Toxicology, 94, 1173-1190. >https://doi.org/10.1007/s00204-020-02698-2 Jiang, X., Tang, Q., Zhang, J., Wang, H., Bai, L., Meng, P., et al. (2018) Autophagy-Dependent Release of Zinc Ions Is Critical for Acute Lung Injury Triggered by Zinc Oxide Nanoparticles. Nanotoxicology, 12, 1068-1091. >https://doi.org/10.1080/17435390.2018.1513094 Meng, P., Zhang, S., Jiang, X., Cheng, S., Zhang, J., Cao, X., et al. (2020) Arsenite Induces Testicular Oxidative Stress in Vivo and in Vitro Leading to Ferroptosis. Ecotoxicology and Environmental Safety, 194, Article ID: 110360. >https://doi.org/10.1016/j.ecoenv.2020.110360 Zhang, Y., Tu, B., Jiang, X., Xu, G., Liu, X., Tang, Q., et al. (2019) Exposure to Carbon Black Nanoparticles during Pregnancy Persistently Damages the Cerebrovascular Function in Female Mice. Toxicology, 422, 44-52. >https://doi.org/10.1016/j.tox.2019.04.014 Ndrepepa, G. (2019) Myeloperoxidase—A Bridge Linking Inflammation and Oxidative Stress with Cardiovascular Disease. Clinica Chimica Acta, 493, 36-51. >https://doi.org/10.1016/j.cca.2019.02.022 Zheng, J., Jiao, S., Li, Q., Jia, P., Yin, H., Zhao, X., et al. (2017) Antrodia Cinnamomea Oligosaccharides Suppress Lipopolysaccharide-Induced Inflammation through Promoting O-Glcnacylation and Repressing P38/Akt Phosphorylation. Molecules, 23, Article No. 51. >https://doi.org/10.3390/molecules23010051 Rossol, M., Heine, H., Meusch, U., Quandt, D., Klein, C., Sweet, M.J., et al. (2011) LPS-Induced Cytokine Production in Human Monocytes and Macrophages. Critical Reviews™ in Immunology, 31, 379-446. >https://doi.org/10.1615/critrevimmunol.v31.i5.20 Schletter, J., Heine, H., Ulmer, A.J. and Rietschel, E.T. (1995) Molecular Mechanisms of Endotoxin Activity. Archives of Microbiology, 164, 383-389. >https://doi.org/10.1007/bf02529735 Spits, H. and Cupedo, T. (2012) Innate Lymphoid Cells: Emerging Insights in Development, Lineage Relationships, and Function. Annual Review of Immunology, 30, 647-675. >https://doi.org/10.1146/annurev-immunol-020711-075053 Halim, T.Y.F., Steer, C.A., Mathä, L., Gold, M.J., Martinez-Gonzalez, I., McNagny, K.M., et al. (2014) Group 2 Innate Lymphoid Cells Are Critical for the Initiation of Adaptive T Helper 2 Cell-Mediated Allergic Lung Inflammation. Immunity, 40, 425-435. >https://doi.org/10.1016/j.immuni.2014.01.011 Spits, H., Bernink, J.H. and Lanier, L. (2016) NK Cells and Type 1 Innate Lymphoid Cells: Partners in Host Defense. Nature Immunology, 17, 758-764. >https://doi.org/10.1038/ni.3482 Hirose, S., Wang, S., Tormanen, K., Wang, Y., Tang, J., Akbari, O., et al. (2019) Roles of Type 1, 2, and 3 Innate Lymphoid Cells in Herpes Simplex Virus 1 Infection in Vitro and in Vivo. Journal of Virology, 93, e00523-19. >https://doi.org/10.1128/jvi.00523-19 Zhao, M., Chen, Y., Wang, C., Xiao, W., Chen, S., Zhang, S., et al. (2019) Systems Pharmacology Dissection of Multi-Scale Mechanisms of Action of Huo-Xiang-Zheng-Qi Formula for the Treatment of Gastrointestinal Diseases. Frontiers in Pharmacology, 9, Article No. 1448. >https://doi.org/10.3389/fphar.2018.01448 Cong, S., Xiang, L., Yuan, X., Bai, D. and Zhang, X. (2019) Notoginsenoside R1 Up-Regulates Microrna-132 to Protect Human Lung Fibroblast MRC-5 Cells from Lipopolysaccharide-Caused Injury. International Immunopharmacology, 68, 137-144. >https://doi.org/10.1016/j.intimp.2018.12.065 He, H., Wu, Y., Nie, Y., Wang, J., Ge, M. and Qian, F. (2017) LYRM03, an Ubenimex Derivative, Attenuates Lps-Induced Acute Lung Injury in Mice by Suppressing the TLR4 Signaling Pathway. Acta Pharmacologica Sinica, 38, 342-350. >https://doi.org/10.1038/aps.2016.141 Chen, S., Chen, H., Du, Q. and Shen, J. (2020) Targeting Myeloperoxidase (MPO) Mediated Oxidative Stress and Inflammation for Reducing Brain Ischemia Injury: Potential Application of Natural Compounds. Frontiers in Physiology, 11, Article No. 433. >https://doi.org/10.3389/fphys.2020.00433 Lei, J., Wei, Y., Song, P., Li, Y., Zhang, T., Feng, Q., et al. (2018) Cordycepin Inhibits LPS-Induced Acute Lung Injury by Inhibiting Inflammation and Oxidative Stress. European Journal of Pharmacology, 818, 110-114. >https://doi.org/10.1016/j.ejphar.2017.10.029 Chistiakov, D.A., Killingsworth, M.C., Myasoedova, V.A., Orekhov, A.N. and Bobryshev, Y.V. (2017) Cd68/Macrosialin: Not Just a Histochemical Marker. Laboratory Investigation, 97, 4-13. >https://doi.org/10.1038/labinvest.2016.116 Trabanelli, S., Gomez‐Cadena, A., Salomé, B., Michaud, K., Mavilio, D., Landis, B.N., et al. (2018) Human Innate Lymphoid Cells (ILCs): Toward a Uniform Immune‐Phenotyping. Cytometry Part B: Clinical Cytometry, 94, 392-399. >https://doi.org/10.1002/cyto.b.21614 Ardain, A., Porterfield, J.Z., Kløverpris, H.N. and Leslie, A. (2019) Type 3 ILCs in Lung Disease. Frontiers in Immunology, 10, Article No. 92. >https://doi.org/10.3389/fimmu.2019.00092 Nalos, M., Huang, S., Sluyter, R., Khan, A., Santner-Nanan, B., Nanan, R., et al. (2008) “Host Tissue Damage” Signal ATP Impairs IL-12 and IFNγ Secretion in LPS Stimulated Whole Human Blood. Intensive Care Medicine, 34, 1891-1897. >https://doi.org/10.1007/s00134-008-1156-y Wang, L., Zhang, K., Han, S., Zhang, L., Bai, H., Bao, F., et al. (2019) Constituents Isolated from the Leaves of Glycyrrhiza Uralansis and Their Anti-Inflammatory Activities on LPS-Induced RAW264.7 Cells. Molecules, 24, Article No. 1923. >https://doi.org/10.3390/molecules24101923 Liao, S., Li, P., Wang, J., Zhang, Q., Xu, D., Yang, M., et al. (2016) Protection of Baicalin against Lipopolysaccharide Induced Liver and Kidney Injuries Based on (1)H NMR Metabolomic Profiling. Toxicology Research, 5, 1148-1159. >https://doi.org/10.1039/c6tx00082g
Baidu
map