| 引用本文: |
买买提明·买合木提, 乃比江·阿不拉, 海白尔·火加艾合买提, 马强强, 乃比江·麦图荪.基于UHPLC-Q-Orbitrap-MS的爱维心口服液化学成分鉴定及其抗心肌缺血再灌注损伤的作用机制研究[J].湖南中医药大学学报,2025,45(7):1210-1220[点击复制] |
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| 基于UHPLC-Q-Orbitrap-MS的爱维心口服液化学成分鉴定及其抗心肌缺血再灌注损伤的作用机制研究 |
| 买买提明·买合木提,乃比江·阿不拉,海白尔·火加艾合买提,马强强,乃比江·麦图荪 |
| (新疆和田学院新疆和田特色中医药研究重点实验室, 新疆 和田 848000;新疆和田学院新疆和田中药民族医药工程技术研究中心, 新疆 和田 848000;新疆和田学院基础医学院, 新疆 和田 848000) |
| 摘要: |
| 目的 探讨爱维心口服液（AWX）缓解大鼠缺血再灌注心肌损伤的药效物质及保护作用。方法 采用UHPLC-Q-Orbitrap-MS对AWX的化学成分进行鉴定，并从ETCM数据库中获得其作用靶点；通过GeneCards、OMIM等数据查询库中筛选MIRI相关靶点；通过STRING数据库进行蛋白质-蛋白质相互作用（PPI）分析，构建PPI网络。通过David数据库分析“AWX成分－靶点”及其参与的生物学过程及信号通路，采用Cytoscape 3.9.1软件构建“AWX成分-疾病-靶点”网络。75只雄性SD大鼠随机分为正常组、模型组以及AWX低（2 mL/kg）、中（4 mL/kg）、高剂量（8 mL/kg）组，连续药物干预7 d后采用左冠状动脉前降支结扎的方式建立大鼠模型，并继续灌胃14 d后腹主动脉取血。ELISA检测大鼠血清乳酸脱氢酶（LDH）、肌酸激酶（CK）变化、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）水平的变化；检测心肌组织丙二醛（MDA）、谷胱甘肽过氧化物酶（GPX）含量；HE染色观察心肌病理改变； Western blot和TUNEL等方法 检测心肌细胞凋亡及相关蛋白表达水平。结果 从AWX中共推断鉴定出52个化学成分，其中筛选活性成分22个，药物疾病交集基因109个，其中蛋白激酶B1（AKT1）、β-胞质肌动蛋白（ACTB）、雌激素受体1（ESR1）等靶点AWX治疗MIRI密切相关，富集分析预测AWX治疗MIRI主要涉及三羧酸循环等信号通路等。动物实验验证结果显示，与模型组相比，AWX各剂量组MIRI大鼠心肌组织损伤程度减轻，线粒体形态改善，凋亡信号降低；AWX中、高剂量组血清LDH、CK、心肌组织MDA含量降低（P<0.05，P<0.01），心肌组织GPX水平升高（P<0.05，P<0.01）；AWX高剂量组血清IL-6水平明显降低（P<0.05）；AWX中、高剂量组MIRI大鼠心肌组织p-Akt/Akt1、BCL2/BAX蛋白比值提高（P<0.05）。结论 AWX通过多成分、多靶点、多通路发挥防治缺血再灌注大鼠心肌保护作用，尤其是可通过激活AKT1，抑制心肌细胞凋亡，从而减少心肌细胞的丢失而发挥保护心肌作用。 |
| 关键词: 心肌缺血再灌注损伤 爱维心口服液 化学成分 线粒体功能 细胞凋亡 心肌保护作用 |
| DOI：10.3969/j.issn.1674-070X.2025.07.003 |
| 投稿时间：2025-03-04 |
| 基金项目:和田地区本级技术研究与开发计划项目（202113）；新疆和田学院校企合作项目（2024JSFW-08）；新疆和田学院校级课题重点项目（2021XK12）。 |
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| Chemical components identification of Aiweixin oral liquid by UHPLC-Q-Orbitrap-MS and its protective mechanism of action against myocardial injury in ischemia-reperfusion rats |
| Maimaitiming Maihemuti, Naibijiang Abula, Haibai'er Huojia'aihemaiti, MA Qiangqiang, Naibijiang Maitusun |
| (Xinjiang Key Laboratory of Hetian Characteristic Chinese Medicine Research, Xinjiang Hetian College, Hetian, Xinjiang 848000, China;Hetian Chinese Medicine and Ethnic Medicine Engineering Technology Research Center, Xinjiang Hetian College, Hetian, Xinjiang 848000, China;School of Basic Medicine, Xinjiang Hetian College, Hetian, Xinjiang 848000, China) |
| Abstract: |
| Objective To explore the pharmacodynamic substances and protective effects of Aiweixin (AWX) oral liquid in alleviating myocardial ischemia-reperfusion injury (MIRI) in rats. Methods The chemical components of AWX were identified using UHPLC-Q-Orbitrap-MS, and its potential targets were obtained from the ETCM database. MIRI-related targets were screened from databases such as GeneCards and OMIM. Protein-protein interaction (PPI) analysis was conducted using the STRING database to construct a PPI network. The "AWX component-target" interactions, along with their involved biological processes and signaling pathways, were analyzed using the David database. An "AWX component-disease-target" network was constructed using Cytoscape 3.9.1 software. Seventy-five male SD rats were randomly divided into normal group, model group, and low- (2 mL/kg), medium- (4 mL/kg), and high-dose (8 mL/kg) AWX groups. After seven days of continuous drug intervention, a rat model was established by ligating the left anterior descending coronary artery, followed by another 14 days of intragastric administration. Blood samples were collected from the abdominal aorta. ELISA was used to determine changes in serum lactate dehydrogenase (LDH), creatine kinase (CK), interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels in rats. The content of malondialdehyde (MDA) and glutathione peroxidase (GPX) in myocardial tissue was measured. HE staining was used to observe myocardial pathological changes, and Western blot and TUNEL methods were used to check myocardial cell apoptosis and related protein expression levels. Results A total of 52 chemical components were identified from AWX, of which 22 active components were screened. There were 109 intersecting genes between drug and disease targets. Targets such as Akt1, ACTB, and ESR1 were closely related to AWX treatment for MIRI. Enrichment analysis predicted that AWX treatment for MIRI mainly involved signaling pathways such as the tricarboxylic acid cycle. Animal experimental validation results showed that compared with the model group, the degree of myocardial tissue damage was reduced, the mitochondrial morphology was improved, and the apoptotic signals were reduced in the AWX groups at all doses. The levels of serum LDH, CK, and MDA content in myocardial tissue decreased (P<0.05, P<0.01), and the level of GPX in myocardial tissue increased in the medium- and high-dose AWX groups (P<0.05, P<0.01). Compared with the model group, the serum IL-6 level significantly decreased in the high-dose AWX group (P<0.05). The protein expression ratios of p-Akt/Akt1 and BCL2/BAX in the myocardial tissue of MIRI rats increased in the medium- and high-dose AWX groups compared with the model group (P<0.05). Conclusion AWX exhibits myocardial protective effects against ischemia-reperfusion injury through multiple components, targets, and pathways. In particular, it can activate Akt1 and inhibit myocardial cell apoptosis, thereby reducing the loss of myocardial cells and exerting protective effects on the myocardium. |
| Key words: myocardial ischemia-reperfusion injury aiweixin oral liquid chemical component mitochondrial function apoptosis cardioprotective effect |
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