山东大学学报 (医学版) ›› 2022, Vol. 60 ›› Issue (11): 70-81.doi: 10.6040/j.issn.1671-7554.0.2022.0911
范晓艳1,王元耕2,陈泽涛3
FAN Xiaoyan1, WANG Yuangeng2, CHEN Zetao3
摘要: 目的 利用网络药理学-分子对接技术探究黄芪桂枝五物汤治疗心力衰竭的作用机制。 方法 通过中药系统药理学数据库与分析平台(TCMSP)获得黄芪桂枝五物汤药物成分,通过Uniprot 数据库获得药物成分对应靶点,通过GeneCard、OMIM、pharmgkb、TTD、DrugBank数据库获得心衰的相关靶点,利用R软件获取黄芪桂枝五物汤与心衰的共同靶点。利用R、Cytoscape、Autodock、pymol软件进行蛋白相互作用(PPI)、基因本体(GO)、京都基因与基因组百科全书(KEGG)、分子对接等分析。 结果 获得黄芪桂枝五物汤靶点84个,心衰差异基因1 430个,共同靶点118个。共同靶点的通路富集分析显示主要与丝裂原活化蛋白激酶(MAPK)、白细胞介素-17(IL-17)等信号通路相关,分子对接结果显示,心衰核心靶点与黄芪桂枝五物汤主要成分亲和力较好,能够有效自由结合。 结论 黄芪桂枝五物汤中的槲皮素、异鼠李素、刺芒柄花素等成分能够通过抗氧化应激、抗纤维化等作用发挥治疗心衰的作用。黄芪桂枝五物汤可通过多层次、多途径、多靶点发挥对心衰的治疗作用。
中图分类号:
[1] | 王华,梁延春.中国心力衰竭诊断和治疗指南2018[J].中华心血管病杂志, 2018, 46(10): 760-789. |
[2] | McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure [J]. Eur Heart J, 2021, 42(36): 3599-3726. |
[3] | 李星星. 益气活血利水方改善冠心病慢性心衰患者心功能及生存质量的研究[D]. 北京:北京中医药大学, 2020. |
[4] | 孙碧鸿. 补阳还五汤化裁对慢性心力衰竭患者生存质量及预后的影响[D]. 哈尔滨:黑龙江中医药大学, 2020. |
[5] | 张裕珍, 姚娜. 黄芪桂枝五物汤治疗急性心肌梗死临床观察[J]. 光明中医, 2021, 36(22): 3832-3834. ZHANG Yuzhen, YAO Na. Clinical observation on Huangqi Guizhi Wuwu Decoction on acute myocardial infarction [J]. Guangming Journal of Chinese Medicine, 2021, 36(22): 3832-3834. |
[6] | 沈中琪, 黎丽娴, 谭景光, 等. 黄芪桂枝五物汤治疗气虚血瘀型慢性心力衰竭运动耐量的临床观察[J]. 云南中医中药杂志, 2019, 40(5): 54-56. SHEN Zhongqi, LI Lixian, TAN Jingguang, et al. Clinical observation on Huangqi Guizhi Wuwu Decoction in treating exercise tolerance of chronic heart failure caused by qi deficiency and blood stasis [J]. Yunnan Journal of Traditional Chinese Medicine and Materia Medica, 2019, 40(5): 54-56. |
[7] | 张润萍, 胡明丽. 黄芪桂枝五物合真武汤加减治疗慢性心力衰竭临床观察[J]. 光明中医, 2021, 36(8): 1224-1226. ZHANG Runping, HU Mingli. Observation on the curative effect of Huangqi Guizhi Wuwu Decoction and Zhenwu Decoction in the treatment of chronic heart failure [J]. Guangming Journal of Chinese Medicine, 2021, 36(8): 1224-1226. |
[8] | 黄圣, 弓航, 赵乐滢, 等. 基于网络药理学和分子对接技术探究生脉注射液对急性心肌梗死与短暂性脑缺血发作异病同治的机制[J]. 中国药师, 2021, 24(10): 1838-1846. HUANG Sheng, GONG Hang, ZHAO Leying, et al. Exploration of the same treatment for different diseases mechanism of Shengmai injection in treating acute myocardial infarction and transient ischemia attack based on network pharmacology and molecu-lar docking technology [J]. Transactions of Nonferrous Metals Society of China, 2021, 24(10): 1838-1846. |
[9] | 蔡萧君, 王磊, 江柏华, 等. 基于液相色谱-四极杆/飞行时间质谱血液代谢组学的黄芪桂枝五物汤干预血瘀证大鼠的研究[J]. 中国医院用药评价与分析, 2021, 21(11): 1308-1312. CAI Xiaojun, WANG Lei, JIANG Bai|hua, et al. Intervention of Huangqi Guizhi Wuwu Decoction in rats with blood stasis syndrome based on liquid chromatography-quadrupole-time of flight-mass spectrometry blood metabolomics [J]. Evaluation and Analysis of Drug-Use in Hospitals of China, 2021, 21(11): 1308-1312. |
[10] | 王淑香. p38MAPK在心力衰竭发病机制中的研究进展[J]. 医学综述, 2014, 20(19): 3486-3488. WANG Shuxiang. Research progress of the role of p38MAPK in the pathogenesis of heart failure [J]. Medical Recapitulate, 2014, 20(19): 3486-3488. |
[11] | González A, Schelbert EB, Díez J, et al. Myocardial interstitial fibrosis in heart failure: biological and translational perspectives [J]. J Am Coll Cardiol, 2018, 71(15): 1696-1706. |
[12] | Yamagata K. Polyphenols regulate endothelial functions and reduce the risk of cardiovascular disease [J]. Curr Pharm Des, 2019, 25(22): 2443-2458. |
[13] | Anand David AV, Arulmoli R, Parasuraman S. Overviews of biological importance of quercetin: a bioactive flavonoid [J]. Pharmacogn Rev, 2016, 10(20): 84-89. |
[14] | Batiha GE, Beshbishy AM, Ikram M, et al. The pharmacological activity, biochemical properties, and pharmacokinetics of the major natural polyphenolic flavonoid: quercetin [J]. Foods, 2020, 9(3): E374. |
[15] | Mirsafaei L, Reiner Ž, Shafabakhsh R, et al. Molecular and biological functions of quercetin as a natural solution for cardiovascular disease prevention and treatment [J]. Plant Foods Hum Nutr, 2020, 75(3): 307-315. |
[16] | Sharma A, Parikh M, Shah H, et al. Modulation of Nrf2 by quercetin in doxorubicin-treated rats [J]. Heliyon, 2020, 6(4): e03803. |
[17] | Ma C, Xia R, Yang S, et al. Formononetin attenuates atherosclerosis via regulating interaction between KLF4 and SRA in apoE-/- mice [J]. Theranostics, 2020, 10(3): 1090-1106. |
[18] | Tay KC, Tan LT, Chan CK, et al. Formononetin: a review of its anticancer potentials and mechanisms [J]. Front Pharmacol, 2019, 10: 820. doi: 10.3389/fphar.2019.00820. |
[19] | Ma X, Wang J. Formononetin: a pathway to protect neurons [J]. Front Integr Neurosci, 2022, 16: 908378. doi: 10.3389/fnint.2022.908378. |
[20] | Wang DS, Yan LY, Yang DZ, et al. Formononetin ameliorates myocardial ischemia/reperfusion injury in rats by suppressing the ROS-TXNIP-NLRP3 pathway [J]. Biochem Biophys Res Commun, 2020, 525(3): 759-766. |
[21] | Aonuma K, Ferdousi F, Xu D, et al. Effects of isorhamnetin in human amniotic epithelial stem cells in vitro and its cardioprotective effects in vivo [J]. Front Cell Dev Biol, 2020, 8: 578197. doi: 10.3389/fcell.2020.578197. |
[22] | Gao L, Yao R, Liu Y, et al. Isorhamnetin protects against cardiac hypertrophy through blocking PI3K-AKT pathway [J]. Mol Cell Biochem, 2017, 429(1-2): 167-177. |
[23] | Du Y, Han J, Zhang H, et al. Kaempferol prevents against ang II-induced cardiac remodeling through attenuating ang II-induced inflammation and oxidative stress [J]. J Cardiovasc Pharmacol, 2019, 74(4): 326-335. |
[24] | Puzianowska-Kuznicka M. ESR1 in myocardial infarction [J]. Clin Chim Acta, 2012, 413(1-2): 81-87. |
[25] | Kolur V, Vastrad B, Vastrad C, et al. Identification of candidate biomarkers and therapeutic agents for heart failure by bioinformatics analysis [J]. BMC Cardiovasc Disord, 2021, 21(1): 329. |
[26] | Peter I, Huggins GS, Shearman AM, et al. Age-related changes in echocardiographic measurements: association with variation in the estrogen receptor-alpha gene [J]. Hypertension, 2007, 49(5): 1000-1006. |
[27] | Yokota T, Li J, Huang J, et al. p38 Mitogen-activated protein kinase regulates chamber-specific perinatal growth in heart [J]. J Clin Invest, 2020, 130(10): 5287-5301. |
[28] | 段卡丹, 张守彦, 李松森, 等. MAPK信号通路在转化生长因子β1诱导心肌成纤维细胞趋化运动中的作用[J]. 中国动脉硬化杂志, 2020, 28(11): 966-971. DUAN Kadan, ZHANG Shouyan, LI Songsen, et al. Roles of MAPK signaling pathway on chemotaxis of cardiac fibroblasts induced by transforming growth factor-Β [J]. Chinese Journal of Arteriosclerosis, 2020, 28(11): 966-971. |
[29] | 刘婷婷, 张淑萍, 覃筱燕, 等. MAPK信号转导通路与神经损伤研究进展[J]. 中国公共卫生, 2016, 32(2): 248-254. LIU Tingting, ZHANG Shuping, QIN Xiaoyan, et al. Progress in studies on MAPK signal transduction pathway and nerve injury [J]. Chinese Journal of Public Health, 2016, 32(2): 248-254. |
[30] | Sinfield JK, Das A, ORegan DJ, et al. p38 MAPK alpha mediates cytokine-induced IL-6 and MMP-3 expression in human cardiac fibroblasts [J]. Biochem Biophys Res Commun, 2013, 430(1): 419-424. |
[31] | Romero-Becerra R, Santamans AM, Folgueira C, et al. p38 MAPK pathway in the heart: new insights in health and disease [J]. Int J Mol Sci, 2020, 21(19): E7412. |
[32] | Lei J, Xue S, Wu W, et al. Sdc1 overexpression inhibits the p38 MAPK pathway and lessens fibrotic ventricular remodeling in MI rats [J]. Inflammation, 2013, 36(3): 603-615. |
[33] | Gallo S, Vitacolonna A, Bonzano A, et al. ERK: a key player in the pathophysiology of cardiac hypertrophy [J]. Int J Mol Sci, 2019, 20(9): 2164. |
[34] | 杨水健, 张鑫, 杨大春. p38 MAPK及基质金属蛋白酶在心力衰竭病人心肌重构中的意义[J]. 中国病理生理杂志, 2007, 23(8): 1631-1632. YANG Shuijian, ZHANG Xin, YANG Dachun. Significance of p38 MAPK and matrix metalloproteinases in myocardial remodeling of patients with contgestive heart failure [J]. Chinese Journal of Pathophysiology, 2007, 23(8): 1631-1632. |
[35] | Craige SM, Chen K, Blanton RM, et al. JNK and cardiometabolic dysfunction [J]. Biosci Rep, 2019, 39(7): BSR20190267. |
[36] | Cai H, Liu Y, Men H, et al. Protective mechanism of humanin against oxidative stress in aging-related cardiovascular diseases [J]. Front Endocrinol(Lausanne), 2021, 12: 683151. doi:10.3389/fendo.2021.683151. |
[37] | 周学红, 张晶. 白细胞介素-6和白细胞介素-17与急性心肌梗死相关性的研究进展[J]. 实用临床医药杂志, 2020, 24(1): 128-132. ZHOU Xuehong, ZHANG Jing. Research progress on the correlation between interleukin-6, interleukin-17 and acute myocardial infarction [J]. Journal of Clinical Medicine in Practice, 2020, 24(1): 128-132. |
[38] | Rai A, Narisawa M, Li P, et al. Adaptive immune disorders in hypertension and heart failure: focusing on T-cell subset activation and clinical implications [J]. J Hypertens, 2020, 38(10): 1878-1889. |
[39] | Xue GL, Li DS, Wang ZY, et al. Interleukin-17 upregulation participates in the pathogenesis of heart failure in mice via NF-κB-dependent suppression of SERCA2a and Cav1.2 expression [J]. Acta Pharmacologica Sinica, 2021, 42(11): 1780-1789. |
[40] | Zhou SF, Yuan J, Liao MY, et al. IL-17A promotes ventricular remodeling after myocardial infarction [J]. J Mol Med(Berl), 2014, 92(10): 1105-1116. |
[41] | Chang SL, Hsiao YW, Tsai YN, et al. Interleukin-17 enhances cardiac ventricular remodeling via activating MAPK pathway in ischemic heart failure [J]. J Mol Cell Cardiol, 2018, 122: 69-79. doi:10.1016/j.yjmcc.2018.08.005. |
[42] | Hsiao YW, Tsai YN, Huang YT, et al. Rhodiola crenulata reduces ventricular arrhythmia through mitigating the activation of IL-17 and inhibiting the MAPK signaling pathway [J]. Cardiovasc Drugs Ther, 2021, 35(5): 889-900. |
[1] | 董雪,赵霞,程子捷,韩毅. 左西孟旦和米力农治疗重症心力衰竭合并肾损伤患者711例的药物经济学评价[J]. 山东大学学报 (医学版), 2022, 60(4): 91-98. |
[2] | 李明波,黄燕波,刘俊城,任东成,谭成双,徐继禧,丁金勇. 黄芪桂枝五物汤治疗强直性脊柱炎的网络药理学探讨[J]. 山东大学学报 (医学版), 2022, 60(3): 29-38. |
[3] | 兰洪涛,贾旭,童洲杰,郑曼,胡伯昂,钟明,张薇,王志浩. 无选择性152例成年慢性心力衰竭患者再入院的危险因素[J]. 山东大学学报 (医学版), 2021, 59(4): 63-69. |
[4] | 于莹,张功,刘晶,颜世童,韩涛,黄海量. 基于网络药理学和分子对接方法探析黄芪预防新型冠状病毒肺炎的潜在作用机制[J]. 山东大学学报 (医学版), 2021, 59(4): 6-16. |
[5] | 张淑莹,武晓峰,郭丽敏,乔温,彭洁琼,李大庆. 两种阿霉素心力衰竭模型及心功能进展的评估[J]. 山东大学学报 (医学版), 2020, 58(12): 1-7. |
[6] | 高源,季伟,肖丹,刘井,彭丹冰,季春. 基于网络药理学预测沙苑子的抗炎作用机制[J]. 山东大学学报 (医学版), 2019, 57(9): 59-68. |
[7] | 米传晓,刘军妮,邹承伟,周南南. 血清可溶性肿瘤因子2抑制剂、半乳糖凝集素-3蛋白水平在慢性心衰分级及预后中的应用[J]. 山东大学学报 (医学版), 2019, 57(1): 62-67. |
[8] | 陈欧,李国勇,刘爱红,朱晓波,陈少杰,王一彪. 网络药理学预测麻黄治疗哮喘的抗炎作用机制[J]. 山东大学学报 (医学版), 2019, 57(1): 55-61. |
[9] | 姜蕴珊,谈红,李晓燕,苏莉,张国明,张红明,孟楠. 培哚普利对慢性心力衰竭患者血浆miR-423-5p的调控及对心功能的影响[J]. 山东大学学报(医学版), 2016, 54(8): 55-59. |
[10] | 许天一,吴萍,王爱玲,陈丽萍. 米力农雾化治疗小儿重症肺炎合并心力衰竭的疗效[J]. 山东大学学报(医学版), 2016, 54(7): 88-90. |
[11] | 尹黎波, 李慧萍. 曲美他嗪治疗重症疾患并发 慢性心力衰竭患者的临床疗效[J]. 山东大学学报(医学版), 2014, 52(S2): 99-100. |
[12] | 刘霄岩. 米力农治疗难治性心力衰竭80例临床观察[J]. 山东大学学报(医学版), 2014, 52(S2): 61-61. |
[13] | 周长学. 多巴酚丁胺联合参附注射液治疗扩张型心肌病重度心力衰竭(附典型病例1例)[J]. 山东大学学报(医学版), 2014, 52(S1): 132-133. |
[14] | 姜红梅1,2,陈文强1. 老年冠心病心衰患者运动康复治疗中心理干预的临床意义[J]. 山东大学学报(医学版), 2014, 52(4): 85-88. |
[15] | 刘善文1,王福1, 李彬2,耿海华3,李彩娥4,许哲5,李睿1,肖洁1,张森1,季晓平1. 大鼠骨髓间充质干细胞exosome提取及其心肌细胞H9C2靶向作用的实验探索[J]. 山东大学学报(医学版), 2013, 51(9): 1-7. |
|