基于网络药理学研究丹参-川芎抗脑缺血再灌注损伤作用机制及试验验证

doi:10.16431/j.cnki.1671-7236.2022.09.038

Abstract

Abstract: 【Objective】 The experiment was aimed to study the effective components and corresponding gene targets of Salvia miltiorrhiza and Ligusticum chuanxiong in the treatment of ischemic stroke through network pharmacology, and to explore its mechanism of action.【Method】 Using Traditional Chinese Medicine System Pharmacology Enumeration Platform (TCMSP), GeneCards and OMIM database, the potential targets of Salvia miltiorrhiza and Ligusticum chuanxiong for the treatment of ischemic stroke were screened, and GO function and KEGG pathway enrichment analysis were carried out.The sham-operated group, the model group, and the low-dose, medium-dose and high-dose Salvia miltiorrhiza-Ligusticum chuanxiong groups were set up respectively, and the cerebral ischemia-reperfusion model rats prepared by suture were intervened by means of preventive and therapeutic administration.The 24-h blood reperfusion model rats were scored for neurological function by Zea-longa method, and hematoxylin-eosin (HE) staining was used to observe the pathological changes of brain tissue for preliminary verification.【Result】 In this study, a total of 72 main active ingredients of Salvia miltiorrhiza-Ligusticum chuanxiong pairs were screened, 7 from Ligusticum chuanxiong, 65 from Salvia miltiorrhiza, and 1 972 target genes for ischemic stroke.There were 94 common targets, including IL6, IL10, TNF, MMP9, VEGFA, CASP3, etc.The results of GO function and KEGG pathway enrichment suggested that the treatment of ischemic stroke by Salvia miltiorrhiza-Ligusticum chuanxiong was related to PI3K-Akt, cGMP-PKG, VEGF and other signal pathways.Animal experiments showed that Salvia miltiorrhiza-Ligusticum chuanxiong could reduce the pathological changes of brain tissue, reduce neurological deficits, and improve cerebral ischemia-reperfusion injury.【Conclusion】 Salvia miltiorrhiza-Ligusticum chuanxiong medicine pair might improve cerebral ischemia-reperfusion injury through PI3K/Akt signaling pathway, and played an anti-apoptotic effect.

Key words: Salvia miltiorrhiza-Ligusticum chuanxiong; cerebral ischemia-reperfusion; network pharmacology; pharmacological mechanism of action

CLC Number:

S853.74

FU Xueqin, LAN Rui, ZOU Xuhuan, WANG Weiwei, WANG Manman. Action Mechanism of Salvia miltiorrhiza-Ligusticum chuanxiong Against Cerebral Ischemia-reperfusion Injury Based on Network Pharmacology and Experimental Verification[J]. China Animal Husbandry and Veterinary Medicine, 2022, 49(9): 3643-3654.

References

[1] VAHIDINIA Z, KARIMIAN M, JOGHATAEI M T.Neurosteroids and their receptors in ischemic stroke:From molecular mechanisms to therapeutic opportunities[J].Pharmacological Research, 2020, 160:105163.
[2] 薛璐, 董莹, 刘欣琦, 等. 《医林改错》论治缺血性脑中风经验撷要[J]. 四川中医, 2022, 40(4):35-38. XUE L, DONG Y, LIU X Q, et al. Experience of treating ischemic cerebral apoplexy in Yilin Correcting Mistakes[J]. Journal of Sichuan of Traditional Chinese Medicine, 2022, 40(4):35-38. (in Chinese)
[3] 韦园诗, 朱黎霞, 黄星星, 等.基于UPLC-Q/TOF-MS的丹参-川芎对局灶性脑缺血大鼠保护作用的脂质组学研究[J].中草药, 2019, 50(2):408-417. WEI Y S, ZHU L X, HUANG X X, et al.Lipidomic study of protective dffect of Salvia miltiorrhiza and Ligusticum chuanxiong on rats with focal cerebral ischemia injury based on UPLC-Q/TOF-MS[J].Chinese Traditional and Herbal Drugs, 2019, 50(2):408-417.(in Chinese)
[4] 范文慧, 裘五四.丹参川芎嗪注射液对急性颅脑损伤患者炎症因子的影响[J].中国临床药理学杂志, 2017, 33(12):1082-1084. FAN W H, QIU W S.Influence of Salvia miltiorrhiza and ligustrazine injection on inflammatory factor in acute craniocerebral injury patients[J].The Chinese Journal of Clinical Pharmacology, 2017, 33(12):1082-1084.(in Chinese)
[5] 张玉淼, 王红莲, 周宏斌, 等.丹参川芎嗪注射液对缺血性脑卒中患者血流变及外周血BCL-2、BAX、Caspase-3蛋白水平的影响[J].中药材, 2015, 38(9):2003-2005. ZHANG Y M, WANG H L, ZHOU H B, et al.Effects of Salvia miltiorrhiza and ligustrazine injection on hemorheology and peripheral blood BCL-2, BAX and Caspase-3 protein levels in patients with ischemic stroke[J].Journal of Chinese Medicinal Materials, 2015, 38(9):2003-2005.(in Chinese)
[6] 姚文博, 李丰, 石彬彬, 等.系统药理学Ⅲ:在诠释中医药整体作用机制中的应用进展[J].中国实验方剂学杂志, 2020, 26(13):219-227. YAO W B, LI F, SHI B B, et al.Systems pharmacology Ⅲ:Application progress in interpretation of holistic mechanism of traditional Chinese medicine[J].Chinese Journal of Experimental Traditional Medical Formulae, 2020, 26(13):219-227.(in Chinese)
[7] 章洪.丹参-川芎药对的药代动力学研究[D].郑州:河南中医学院, 2015. ZHANG H.Pharmacokinetic research on Salviae miltiorrhizae radix et rhizoma and Chuanxiong rhizoma in compatibility[D].Zhengzhou:Henan College of Traditional Chinese Medicine, 2015.(in Chinese)
[8] 孙青.不同配伍配比对丹参-川芎药对中10个有效成分含量的影响[J].中国药师, 2022, 25(1):154-158. SUN Q.Influence of different compatibility proportions on the dissolution of 10 components drug pair in Salvia miltiorrhiza and Ligusticum chuanxiong[J].China Pharmacist, 2022, 25(1):154-158.(in Chinese)
[9] 张翠英, 章洪, 张盈颖, 等.丹参-川芎不同配比对丹酚酸B和阿魏酸煎出率的影响[J].中国医院药学杂志, 2014, 34(13):1056-1059. ZHANG C Y, ZHANG H, ZHANG Y Y, et al.Effects of the decoctions of Salviae radix et rhizoma and Chuanxiong rhizoma at different ratio on the decocting rate of salvianolic acid B and ferulic acid[J].Chinese Journal of Hospital Pharmacy, 2014, 34(13):1056-1059.(in Chinese)
[10] 徐淑云, 卞如濂, 陈修.药理实验方法学[M].3版.北京:人民卫生出版社, 2001. XU S Y, BIAN R L, CHEN X.Pharmacological Experiment Methodology[M].3rd ed.Beijing:People's Medical Publishing House, 2001.(in Chinese)
[11] LONGA E Z, WEINSTEIN P R, CARLSON S, et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke, 1989, 20(1):84-91.
[12] 王敏, 刘建勋, 姚明江, 等.抗脑缺血后神经损伤中药及其药理学研究进展[J].中国中药杂志, 2020, 45(3):513-517. WANG M, LIU J X, YAO M J, et al.Advances in research on pharmacological and neuroprotective effects of traditional Chinese medicine after cerebral ischemia[J].China Journal of Chinese Materia Medica, 2020, 45(3):513-517.(in Chinese)
[13] PATEL R A G, MCMULLEN P W.Neuroprotection in the treatment of acute ischemic stroke[J].Progress in Cardiovascular Diseases, 2017, 59(6):542-548.
[14] 周惠芬, 万海同, 何昱, 等.丹参-川芎有效成分配伍对氧糖剥夺海马神经元细胞保护作用研究[J].中草药, 2019, 50(6):1372-1381. ZHOU H F, WAN H T, HE Y, et al.Protective effects of compatibility of effective constituents in Salvia miltiorrhiza and Ligusticum chuanxiong on hippocampal neurons injured by oxygen glucose deprivation[J].Chinese Traditional and Herbal Drugs, 2019, 50(6):1372-1381.(in Chinese)
[15] 惠贤瑞, 金强, 何江敏, 等.基于转录组学的冠心宁抗小鼠脑缺血再灌注损伤作用机制研究[J].中国中药杂志, 2022, 47(11):3015-3022. HUI X R, JIN Q, HE J M, et al.Mechanisms of Guanxinning against cerebral ischemia-reperfusion injury mice based on transcriptomic analysis[J].China Journal of Chinese Materia Medica, 2022, 47(11):3015-3022.(in Chinese)
[16] 杨喜忠, 孙静, 孙辉.冠心宁注射液治疗早期脑梗死的观察[J].中国医院药学杂志, 2005, 12:1156-1157. YANG X Z, SUN J, SUN H.Observation of Guanxinning injection in the treatment of early cerebral infarction[J].Chinese Journal of Hospital Pharmacy, 2005, 12:1156-1157.(in Chinese)
[17] 王丽萍, 李雯.丹参川芎注射液联合依达拉奉治疗急性脑梗死的临床疗效[J].临床医学研究与实践, 2018, 3(23):37-38. WANG L P, LI W.Clinical effect of Danshen Chuanxiong injection and edaravone in the treatment of acute cerebral infarction[J].Clinical Research and Practice, 2018, 3(23):37-38.(in Chinese)
[18] 董庆海, 刘慧, 王涵, 等.丹参川芎嗪注射液对急性血瘀模型大鼠血液流变学及血浆中GMP-140、vWF的影响[J].中南药学.2019, 17(7):1044-1046. DONG Q H, LIU H, WANG H, et al.Effect of Danshen Chuangxiongqin injection on hemorheology and plasma GMP-140 and vWF in acute blood stasis model rats[J]. Central South Pharmacy, 2019, 17(7):1044-1046.(in Chinese)
[19] 单晓晓, 洪帮振, 刘洁, 等.丹参化学成分、药理作用、临床应用的研究进展及质量标志物的预测分析[J].中国中药杂志, 2021, 46(21):5496-5511. SHAN X X, HONG B Z, LIU J, et al.Review of chemical composition, pharmacological effects, and clinical application of Salviae miltiorrhizae Radix et rhizoma and prediction of its Q-markers[J].China Journal of Chinese Materia Medica, 2021, 46(21):5496-5511.(in Chinese)
[20] 王钺夫, 徐闯, 崔一喆.基于网络药理学探讨中药复方治疗奶牛子宫内膜炎的作用机制[J].中国畜牧兽医, 2022, 49(4):1545-1555. WANG Y F, XU C, CUI Y Z.Study on the mechanism of traditional Chinese medicine compound in the treamt of endometritis in dairy cows based on network pharmacology[J].China Animal Husbandry & Veterinary Medicine, 2022, 49(4):1545-1555.(in Chinese)
[21] 张晓娟, 张燕丽, 左冬冬.川芎的化学成分和药理作用研究进[J].中医药信息, 2020, 37(6):128-133. ZHANG X J, ZHANG Y L, ZUO D D.Research progress on chemical constituents and pharmacological effects of Ligusticum chuanxiong hort[J].Information on Traditional Chinese Medicine, 2020, 37(6):128-133.(in Chinese)
[22] YUAN J H, PAN F, CHEN J, et al.Neuroprotection by plumbagin involves BDNF-TrkB-PI3K/Akt and ERK1/2/JNK pathways in isoflurane-induced neonatal rats[J].The Journal of Pharmacy and Pharmacology, 2017, 69(7):896-906.
[23] LAN R, XIANG J, ZHANG Y, et al.PI3K/Akt pathway contributes to neurovascular unit protection of Xiao-Xu-Ming decoction against focal cerebral ischemia and reperfusion injury in rats[J].Evidence-based Complementary and Alternative Medicine, 2013, 2013:459467.
[24] 张晓璇, 朱江, 李佳佳, 等.丁苯酞对缺血性脑卒中大鼠脑组织NF-κB p65、IL6、TNF-α表达的影响[J].中国免疫学杂志.2019, 35(15):1825-1828. ZHANG X X, ZHU J, LI J J, et al.Effects of butylphthalide on expression of serum NF-κB p65, IL6 and TNF-α in rats with cerebral ischemic stroke[J].Chinese Journal of Immunology. 2019, 35(15):1825-1828.(in Chinese)
[25] 潘之光, 毛颖, 孙凤艳.血管内皮生长因子促损伤脑内神经血管单元的重构[J].生理学报.2017, 69(1):96-108. PAN Z G, MAO Y, SUN F Y.VEGF enhances reconstruction of neurovascular units in the brain after injury[J].Acta Physiologica Sinica, 2017, 69(1):96-108.(in Chinese)
[26] 宋先兵.17β-雌二醇对去卵巢大鼠局灶性脑缺血的神经保护和认知修复作用及其受体机制[D].合肥:安徽医科大学, 2011. SONG X B.17β-estradiol in ovariectomized rats with focal cerebral ischemia neuroprotection, cognitive rehabilitation and its receptor mechanism[D].Hefei:Anhui Medical University, 2011.(in Chinese)
[27] 陈海, 王建.PI3K/Akt信号通路在缺血性脑卒中后细胞程序性死亡中的研究进展[J].中药药理与临床, 2022, 38(2):247-252. CHEN H, WANG J.Research progress of PI3K/Akt signaling pathway in programmed cell death after ischemic stroke[J].Pharmacology and Clinics of Chinese Materia Medica, 2022, 38(2):247-252.(in Chinese)
[28] LORENZ R, BERTINETTI D, HERBERG F W.cAMP-dependent protein kinase and cGMP-dependent protein kinase as cyclic nucleotide effectors[J].Handbook of Experimental Pharmacology, 2017, 238:105-122.
[29] 潘建玲.电针对脑缺血再灌注模型大鼠总抗氧化能力、cAMP、cGMP调节机理的研究[D].南京:南京中医药大学, 2010. PAN J L.Study on the regulating mechansm of electro-acupuncture on T-AOC, cAMP and cGMP of the cerebral ischemia-reperfusion model rats[D].Nanjing:Nanjing University of Traditional Chinese Medicine, 2010.(in Chinese)
[30] WANG L, ZHANG Z G, ZHANG R L, et al.Activation of the PI3-K/Akt pathway mediates cGMP enhanced-neurogenesis in the adult progenitor cells derived from the subventricular zone[J].Journal of Cerebral Blood Flow and Metabolism, 2005, 25(9):1150-1158.
[31] 朱百科, 王新新, 赵恒.川芎嗪通过激活VEGF介导的PI3K/Akt信号通路缓解大鼠脑缺血再灌注引起的损伤[J].河北医学, 2020, 26(6):912-917. ZHU B K, WANG X X, ZHAO H.Tetramethylpyrazine alleviates cerebral ischemia-reperfusion injury by activating VEGF mediated PI3K/Akt signaling pathway in rats[J].Hebei Medicine, 2020, 26(6):912-917.(in Chinese)

Action Mechanism of Salvia miltiorrhiza-Ligusticum chuanxiong Against Cerebral Ischemia-reperfusion Injury Based on Network Pharmacology and Experimental Verification

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