|
|
基于LASP1、CXCR1探析全真一气汤对COPD大鼠的炎症反应和免疫功能的影响
|
Abstract:
目的：观察全真一气汤对慢性阻塞性肺疾病(COPD)大鼠肺组织LASP1和CXCR1表达的影响，探析全真一气汤对COPD的炎症反应和免疫功能的影响。方法：将18只SD大鼠随机分为中药组和模型组，每组各9只。利用烟熏联合内毒素脂多糖(LPS)构建COPD大鼠模型。模型组每日予0.9%生理盐水灌胃；中药组每日予40%全真一气汤浓缩汤剂灌胃。利用PCR技术检测大鼠肺组织LASP1和CXCR1mRNA水平的变化，Western blot检测大鼠肺组织LASP1和CXCR1蛋白水平的变化。结果：中药组LASP1 mRNA表达丰度为模型组的0.145倍；中药组CXCR1 mRNA表达丰度为模型组的0.614倍。与模型组相比，中药组LASP1、CXCR1蛋白表达水平均显著降低。结论：全真一气汤能通过下调LASP1和CXCR1基因及蛋白的表达，改善COPD大鼠炎症微环境，这可能是其降低COPD引起肺癌发生风险的潜在机制之一。
Objective: To observe the effects of Quanzhen Yiqi Decoction on the expression of LASP1 and CXCR1 in lung tissue of chronic obstructive pulmonary disease (COPD) rats, and to explore the effects of Quanzhen Yiqi Decoction on inflammation and immune function of COPD. Methods: Eighteen SD rats were randomly divided into Chinese medicine group and model group, with 9 rats in each group. COPD rat model was established by smoking combined with lipopolysaccharide (LPS). The model group was given 0.9% normal saline daily. The traditional Chinese medicine group was given 40% Quanzhen Yiqi Decoction concentrated decoction every day. The mrna levels of LASP1 and CXCR1 in rat lung tissue were detected by fluorescence quantitative PCR, and the protein levels of LASP1 and CXCr1 in rat lung tissue were detected by Western blot. Results: The mRNA expression abundance of LASP1 in the Chinese medicine group was 0.145 times that in the model group. The mRNA expression abundance of CXCR1 in the TCM group was 0.614 times of that in the model group. Compared with model group, the protein expression levels of LASP1 and CXCR1 in TCM group were significantly decreased. Conclusions: Quanzhen Yiqi Decoction can inhibit airway inflammation in COPD rats by down-regulating the expressions of LASP1 and CXCR1 genes and proteins, which may be one of the potential mechanisms to reduce the risk of lung cancer caused by COPD.
| [1] | Vogelmeier, C.F., Criner, G.J., Martínez, F.J., et al. (2017) Global Strategy for the Diagnosis, Management, and Preven-tion of Chronic Obstructive Lung Disease 2017 Report: GOLD Executive Summary. Archivos de Bronconeumología, 53,128-149. https://doi.org/10.1016/j.arbr.2017.02.001 |
| [2] | Barreiro, E., Bustamante, V., Curull, V., et al. (2016) Relationships between Chronic Obstructive Pulmonary Disease and Lung Cancer: Biological Insights. Journal of Tho-racic Disease, 8, E1122-E1135.
https://doi.org/10.21037/jtd.2016.09.54 |
| [3] | Bray, F., Ferlay, J., Soerjomataram, I., et al. (2018) Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68, 394-424.
https://doi.org/10.3322/caac.21492 |
| [4] | Salvato, I., Ricciardi, L., Nucera, F., et al. (2023) RNA-Binding Proteins as a Molecular Link between COPD and Lung Cancer. COPD: Journal of Chronic Obstructive Pulmonary Disease, 20, 18-30.
https://doi.org/10.1080/15412555.2022.2107500 |
| [5] | 尚立芝, 季书, 李耀洋, 等. 二陈汤加味对急性加重期COPD患者CXCL8及CXCR1/2蛋白表达的影响[J]. 中国实验方剂学杂志, 2019, 25(24): 1-8. |
| [6] | 李黎, 张文琪, 李强, 等. LASP1和HIF-1α在肺癌中的表达及临床价值[J]. 广东医学, 2020, 41(24): 2569-2573. |
| [7] | Ponce-Gallegos, M., Ramírez-Venegas, A. and Falfán-Valencia, R. (2017) Th17 Profile in COPD Ex-acerbations. International Journal of Chronic Obstructive Pulmonary Disease, 12, 1857-1865.
https://doi.org/10.2147/COPD.S136592 |
| [8] | Paplińska-Goryca, M., Nejman-Gryz, P., Górska, K., et al. (2018) Expression of Inflammatory Mediators in Induced Sputum: Comparative Study in Asthma and COPD. In: Pokorski, M., Ed., Clinical Research Involving Pulmonary Disorders, Springer, Cham, 101-112. https://doi.org/10.1007/5584_2016_165 |
| [9] | 李大治, 王春娥, 陈志斌, 等. 应用基因表达谱芯片分析初步探讨全真一气汤抑制COPD大鼠肺损伤的作用机制[J]. 中医临床研究, 2018, 10(35): 5-9. |
| [10] | Shi, J., Guo, J. and Li, X. (2018) Role of LASP-1, a Novel SOX9 Transcriptional Target, in the Progression of Lung Cancer. International Journal of Oncology, 52, 179-188. https://doi.org/10.3892/ijo.2017.4201 |
| [11] | 王春娥, 陈志斌, 陈可强, 等. 全真一气汤对肾不纳气证慢性阻塞性肺疾病稳定期患者肺功能、运动耐量及MMP-9的影响[J]. 广西中医药, 2017, 40(1): 14-16. |
| [12] | 张晶, 严桂珍. 全真一气汤治疗肾气虚型支气管哮喘缓解期32例疗效观察[J]. 福建中医药, 2016, 47(3): 40-42. |
| [13] | 张晶, 李大治, 严桂珍. 全真一气汤颗粒剂治疗肾不纳气证COPD稳定期患者临床疗效观察[J]. 亚太传统医药, 2014, 10(24): 91-92. |
| [14] | 木亚莎尔？吐逊江, 王雨琳, 曹洪丽. 慢性阻塞性肺疾病合并肺癌共同发病机制[J]. 中国组织化学与细胞化学杂志, 2022, 31(4): 412-416. |
| [15] | 韩勇, 徐晖, 王安辉, 等. 慢性阻塞性肺疾病是肺癌的危险因素[J]. 第四军医大学学报, 2005, 26(2): 146-149. |
| [16] | Lowry, K.P., Gazelle, G.S., Gil-more, M.E., et al. (2015) Personalizing Annual Lung Cancer Screening for Patients with Chronic Obstructive Pulmonary Disease: A Decision Analysis. Cancer, 121, 1556-1562.
https://doi.org/10.1002/cncr.29225 |
| [17] | Kaur, M. and Singh, D. (2013) Neutrophil Chemotaxis Caused by Chronic Obstructive Pulmonary Disease Alveolar Macrophages: The Role of CXCL8 and the Receptors CXCR1/CXCR2. Jour-nal of Pharmacology and Experimental Therapeutics, 347, 173-180. https://doi.org/10.1124/jpet.112.201855 |
| [18] | Belchamber, K. and Donnelly, L.E. (2017) Macrophage Dysfunction in Respiratory Disease. In: Kloc, M., Ed., Macrophages, Springer, Cham, 299-313. https://doi.org/10.1007/978-3-319-54090-0_12 |
| [19] | Vacchini, A., Mortier, A., Proost, P., et al. (2018) Differential Effects of Posttranslational Modifications of CXCL8/Inter- leukin-8 on CXCR1 and CXCR2 Internalization and Signal-ing Properties. International Journal of Molecular Sciences, 19, Article 3768. https://doi.org/10.3390/ijms19123768 |
| [20] | Long, X.X., Ye, Y.N., Zhang, L.J., et al. (2016) IL-8, a Novel Mes-senger to Cross-Link Inflammation and Tumor EMT via Autocrine and Paracrine Pathways (Review). International Journal of Oncology, 48, 5-12.
https://doi.org/10.3892/ijo.2015.3234 |
| [21] | Brat, D.J., Bellail, A.C. and Van Meir, E.G. (2005) The Role of Inter-leukin-8 and Its Receptors in Gliomagenesis and Tumoral Angiogenesis. Neuro-Oncology, 7, 122-133. https://doi.org/10.1215/S1152851704001061 |
| [22] | Veenstra, M. and Ransohoff, R.M. (2012) Chemokine Receptor CXCR2: Physiology Regulator and Neuroinflammation Controller? Journal of Neuroimmunology, 246, 1-9. https://doi.org/10.1016/j.jneuroim.2012.02.016 |
| [23] | 尚立芝, 季书, 石龙涛, 等. 基于CXCL8-CXCR1/2轴探讨二陈汤加味对COPD大鼠的抗炎机制[J]. 中国实验方剂学杂志, 2020, 26(11): 40-48. |
| [24] | McColl, S.R., Kreis, C., DiPersio, J.F., Borgeat, P. and Naccache, P.H. (1989) Involvement of Guanine Nucleotide Binding Proteins in Neutro-phil Activation and Priming by GM-CSF. Blood, 73, 588-591.
https://doi.org/10.1182/blood.V73.2.588.588 |
| [25] | Sozzani, S., Agwu, D.E., Ellenburg, M.D., et al. (1994) Activa-tion of Phospholipase D by Interleukin-8 in Human Neutrophils. Blood, 84, 3895-3901. https://doi.org/10.1182/blood.V84.11.3895.bloodjournal84113895 |
| [26] | Park, C.R., You, D.J., Park, S., et al. (2016) The Accessory Proteins REEP5 and REEP6 Refine CXCR1-Mediated Cellular Responses and Lung Cancer Pro-gression. Scientific Reports, 6, Article No. 39041.
https://doi.org/10.1038/srep39041 |
| [27] | Tomasetto, C., Moog-Lutz, C., Régnier, C.H., et al. (1995) Lasp-1 (MLN 50) Defines a New LIM Protein Subfamily Characterized by the Association of LIM and SH3 Domains. FEBS Letters, 373, 245-249.
https://doi.org/10.1016/0014-5793(95)01040-L |
| [28] | Gao, Q., Tang, L., Wu, L., et al. (2018) LASP1 Promotes Nasopharyngeal Carcinoma Progression through Negatively Regulation of the Tumor Suppressor PTEN. Cell Death & Disease, 9, Article No. 393.
https://doi.org/10.1038/s41419-018-0443-y |
| [29] | Niu, Y., Shao, Z., Wang, H., et al. (2016) LASP1-S100A11 Axis Promotes Colorectal Cancer Aggressiveness by Modulating TGFβ/Smad Signaling. Scientific Reports, 6, Article No. 26112. https://doi.org/10.1038/srep26112 |
| [30] | Zhang, X., Liu, Y., Fan, C., et al. (2017) Lasp1 Promotes Malignant Phenotype of Non-Small-Cell Lung Cancer via Inducing Phosphorylation of FAK-AKT Pathway. Oncotarget, 8, 75102-75113.
https://doi.org/10.18632/oncotarget.20527 |
| [31] | Xue, Q., Jiang, H., Wang, J. and Wei, D.S. (2021) LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway. Canadian Respiratory Journal, 2021, Article ID: 5277409.
https://doi.org/10.1155/2021/5277409 |
| [32] | Raman, D., Sai, J., Neel, N.F., Chew, C.S. and Richmond, A. (2010) LIM and SH3 Protein-1 Modulates CXCR2-Me- diated Cell Migration. PLOS ONE, 5, e10050. https://doi.org/10.1371/journal.pone.0010050 |
| [33] | 赵晓婷, 孙洁, 刘爽, 等. 三阴乳腺癌中CXCR1和CXCR2的表达及临床意义[J]. 中国医科大学学报, 2017, 46(7): 636-639. |
| [34] | 范学亮, 郑鹤, 徐海元, 等. 免疫组化法测定LASP1蛋白在鼻咽癌组织中的表达及影响因素分析[J]. 临床研究, 2020, 28(9): 12-13. |
| [35] | Mantovani, A., Al-lavena, P., Sica, A. and Balkwill, F. (2008) Cancer-Related Inflammation. Nature, 454, 436-444.
https://doi.org/10.1038/nature07205 |
| [36] | Lievense, L.A., Bezemer, K., Aerts, J.G. and Hegmans, J.P.J.J. (2013) Tumor-Associated Macrophages in Thoracic Malignancies. Lung Cancer, 80, 256-262. https://doi.org/10.1016/j.lungcan.2013.02.017 |
| [37] | 李丽杰, 宫晓燕, 王爽. 宫晓燕辨治孤立性肺结节病机思路[J]. 吉林中医药, 2021, 41(3): 359-362. |
| [38] | 郑淑君, 王辛秋, 贾喜花, 等. 国医大师晁恩祥辨治肺癌经验[J]. 中华中医药杂志, 2022, 37(7): 3855-3857. |
| [39] | 杨丽, 郭栴子, 杨小蒨, 等. 从“痰瘀互结”理论谈“炎—癌转化”[J]. 河北中医, 2020, 42(12): 1887-1889. |
| [40] | 夏学传. 全真一气汤探析[J]. 安徽中医学院学报, 1999(5): 21-22. |
| [41] | 迟宇昊, 李暘, 申远. 麦冬化学成分及药理作用研究进展[J]. 新乡医学院学报, 2021, 38(2): 189-192. |
| [42] | 魏海涛, 方秋华, 张炳顺, 等. 白术有效成分及药理作用研究进展[J]. 广东畜牧兽医科技, 2022, 47(6): 40-44, 51. |
| [43] | 陈金鹏, 张克霞, 刘毅, 等. 地黄化学成分和药理作用的研究进展[J]. 中草药, 2021, 52(6): 1772-1784. |
| [44] | 申劲锋, 赵俊. 牛膝多糖的药理研究进展[J]. 天津药学, 2006, 18(1): 59-61. |
| [45] | 边才苗, 杨云斌, 费杰, 等. 五味子提取物体外抑菌作用初探[J]. 浙江中医药大学学报, 2009, 33(1): 122-123. |
| [46] | 荣宝山, 黄凯丽, 袁琳嫣, 等. 乌头类药材化学成分和药理作用研究进展[J]. 中国药事, 2021, 35(8): 932-947. |
| [47] | 孟丽娟, 王学廷, 田敏, 等. 茎叶人参皂甙对肺损伤的保护[J]. 中国临床康复, 2005, 9(15): 136-137. |
