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
DOI: 10.12677/hjbm.2025.151009, PDF,    科研立项经费支持
作者: 邓 悦*, 段鑫昊*, 蒋学君, 高 敏, 苏俊豪, 陈承志, 邱景富#, 张弘扬#：重庆医科大学公共卫生学院，重庆；张 军, 邹 镇：重庆医科大学检验医学院，重庆
关键词: 藿香正气液；脂多糖；急性肺损伤；炎症反应；Huoxiangzhengqi Liquid； Lipopolysaccharide； Acute Lung Injury； Inflammation
摘要: 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。
Abstract: 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.
文章引用：邓悦, 段鑫昊, 蒋学君, 张军, 高敏, 苏俊豪, 邹镇, 陈承志, 邱景富, 张弘扬. 藿香正气液对脂多糖致小鼠急性肺损伤的保护作用[J]. 生物医学, 2025, 15(1): 82-92. https://doi.org/10.12677/hjbm.2025.151009

参考文献

[1] Fan, E., Brodie, D. and Slutsky, A.S. (2018) Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment. JAMA, 319, 698-710. [Google Scholar] [CrossRef] [PubMed]
[2] 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. [Google Scholar] [CrossRef] [PubMed]
[3] 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. [Google Scholar] [CrossRef] [PubMed]
[4] 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.
[5] 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. [Google Scholar] [CrossRef] [PubMed]
[6] 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. [Google Scholar] [CrossRef] [PubMed]
[7] 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. [Google Scholar] [CrossRef] [PubMed]
[8] 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. [Google Scholar] [CrossRef] [PubMed]
[9] 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. [Google Scholar] [CrossRef] [PubMed]
[10] 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. [Google Scholar] [CrossRef] [PubMed]
[11] 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. [Google Scholar] [CrossRef] [PubMed]
[12] 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. [Google Scholar] [CrossRef] [PubMed]
[13] Zhou, P. (2010) Hot Topic: Editorial [Traditional Chinese Medicine] (Ping Zhou). Combinatorial Chemistry & High Throughput Screening, 13, 836. [Google Scholar] [CrossRef] [PubMed]
[14] 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.
[15] Read, B.E. (1930) The Chinese Pharmacopoeia. The Canadian Medical Association Journal, 23, 568-570.
[16] 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. [Google Scholar] [CrossRef] [PubMed]
[17] 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. [Google Scholar] [CrossRef] [PubMed]
[18] 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. [Google Scholar] [CrossRef] [PubMed]
[19] 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. [Google Scholar] [CrossRef] [PubMed]
[20] 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.
[21] 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. [Google Scholar] [CrossRef] [PubMed]
[22] 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. [Google Scholar] [CrossRef] [PubMed]
[23] 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. [Google Scholar] [CrossRef] [PubMed]
[24] 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. [Google Scholar] [CrossRef] [PubMed]
[25] 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. [Google Scholar] [CrossRef] [PubMed]
[26] 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. [Google Scholar] [CrossRef] [PubMed]
[27] Ndrepepa, G. (2019) Myeloperoxidase—A Bridge Linking Inflammation and Oxidative Stress with Cardiovascular Disease. Clinica Chimica Acta, 493, 36-51. [Google Scholar] [CrossRef] [PubMed]
[28] 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. [Google Scholar] [CrossRef] [PubMed]
[29] 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. [Google Scholar] [CrossRef] [PubMed]
[30] Schletter, J., Heine, H., Ulmer, A.J. and Rietschel, E.T. (1995) Molecular Mechanisms of Endotoxin Activity. Archives of Microbiology, 164, 383-389. [Google Scholar] [CrossRef] [PubMed]
[31] Spits, H. and Cupedo, T. (2012) Innate Lymphoid Cells: Emerging Insights in Development, Lineage Relationships, and Function. Annual Review of Immunology, 30, 647-675. [Google Scholar] [CrossRef] [PubMed]
[32] 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. [Google Scholar] [CrossRef] [PubMed]
[33] 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. [Google Scholar] [CrossRef] [PubMed]
[34] 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. [Google Scholar] [CrossRef] [PubMed]
[35] 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. [Google Scholar] [CrossRef] [PubMed]
[36] 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. [Google Scholar] [CrossRef] [PubMed]
[37] 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. [Google Scholar] [CrossRef] [PubMed]
[38] 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. [Google Scholar] [CrossRef] [PubMed]
[39] 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. [Google Scholar] [CrossRef] [PubMed]
[40] 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. [Google Scholar] [CrossRef] [PubMed]
[41] 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. [Google Scholar] [CrossRef] [PubMed]
[42] 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. [Google Scholar] [CrossRef] [PubMed]
[43] 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. [Google Scholar] [CrossRef] [PubMed]
[44] 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. [Google Scholar] [CrossRef] [PubMed]
[45] 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. [Google Scholar] [CrossRef] [PubMed]

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