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Improvement effect of arbutin on myocardial fibrosis model rats and its mechanism
- ZHONGGUO YAOFANG Vol. 35, Issue 5, Pages: 529-535(2024)
- 作者机构：
河南中医药大学医学院，郑州 450046
- 作者简介：
- 基金信息：
DOI：10.6039/j.issn.1001-0408.2024.05.04
CLC： R965;R285.5Published：15 March 2024，
Received：26 August 2023，
Revised：23 December 2023，
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张明昊,吴星霏,吴刘俊等.熊果苷对心肌纤维化模型大鼠的改善作用及机制研究 Δ[J].中国药房,2024,35(05):529-535.
ZHANG Minghao,WU Xingfei,WU Liujun,et al.Improvement effect of arbutin on myocardial fibrosis model rats and its mechanism[J].ZHONGGUO YAOFANG,2024,35(05):529-535.
张明昊,吴星霏,吴刘俊等.熊果苷对心肌纤维化模型大鼠的改善作用及机制研究 Δ[J].中国药房,2024,35(05):529-535. DOI： 10.6039/j.issn.1001-0408.2024.05.04.
ZHANG Minghao,WU Xingfei,WU Liujun,et al.Improvement effect of arbutin on myocardial fibrosis model rats and its mechanism[J].ZHONGGUO YAOFANG,2024,35(05):529-535. DOI： 10.6039/j.issn.1001-0408.2024.05.04.
摘要
目的
2
研究熊果苷对心肌纤维化（MF）模型大鼠的改善作用及机制。
方法
2
采用网络药理学方法预测熊果苷改善MF的潜在靶点并进行分子对接验证。将50只SD大鼠皮下注射异丙肾上腺素（5 mg/kg，每天1次，连续14 d）复制MF模型。将造模成功的大鼠随机分为模型组、卡托普利组（9 mg/kg）和熊果苷低、中、高剂量组（50、100、200 mg/kg），每组10只；另取10只未造模大鼠作为正常组。各组大鼠给予相应药物干预，每天1次，连续28 d。末次给药24 h后，检测大鼠心电图、心脏相关指数[心脏质量指数（HWI）、左心室质量指数（LVWI）]，检测大鼠心肌组织中肌酸激酶（CK）、乳酸脱氢酶（LDH）、N末端前脑钠肽前体（NT-proBNP）、Ⅰ型胶原蛋白（Col Ⅰ）、Col Ⅲ水平，观察大鼠心肌组织病理形态学变化，检测大鼠心肌组织中腺苷脱氨酶（ADA）、腺苷激酶（ADK）蛋白及其mRNA表达水平。
结果
2
网络药理学结果显示，熊果苷改善MF的主要靶点为ADA、ADK。分子对接结果显示，熊果苷与ADA、ADK结合稳定。验证实验结果显示，与模型组比较，各给药组大鼠心电图ST波段和T波的振幅有所恢复，心房出现扑动的症状减轻；HWI（熊果苷中剂量组除外）、LVWI和心肌组织中CK、LDH、NT-proBNP、Col Ⅰ、Col Ⅲ水平均显著降低（
P
＜0.05）；大鼠心肌纤维化程度减轻；心肌组织中ADA、ADK蛋白及其mRNA表达水平均显著升高（
P
＜0.05）。
结论
2
熊果苷可改善MF模型大鼠心脏纤维化和心脏功能，其作用机制可能与上调ADA、ADK蛋白及其mRNA表达，影响核苷酸代谢及胶原生成有关。
Abstract
OBJECTIVE
2
To study the improvement effects of arbutin on myocardial fibrosis （MF） model rats and its mechanism.
METHODS
2
The network pharmacology was used to predict the potential target of arbutin in improving MF and molecular docking was used to validated. Totally 50 SD rats were given isoprenaline subcutaneously （5 mg/kg， once a day， for 14 consecutive days） to induce the MF model. Modeled rats were randomly divided into model group， captopril group （9 mg/kg）， arbutin low-dose， medium-dose and high-dose groups （50， 100， 200 mg/kg）， with 10 rats in each group. Another 10 healthy rats were included as normal group. Each group was given the corresponding drugs， once a day， for 28 consecutive days. Twenty-four hours after the final administration， electrocardiograms and heart-related indexes [heart weight index （HWI）， left ventricular weight index （LVWI）] of rats were detected； the levels of creatine kinase （CK）， lactate dehydrogenase （LDH）， N-terminal pro-brain natriuretic peptide （NT-proBNP） and type Ⅰ collagen （Col Ⅰ） and Col Ⅲ were detected in myocardial tissue of rats； the pathological changes of myocardial tissue were observed， and protein and mRNA expressions of adenosine deaminase （ADA） and adenosine kinase （ADK） were detected in the myocardial tissue of rats.
RESULTS
2
The results of network pharmacology showed that the main targets of arbutin improving MF were ADA and ADK. The results of molecular docking showed that arbutin bind stably with ADA and ADK. The results of experimental verification showed that compared with model group， the amplitude of ST and T waves in electrocardiogram were improved in administration groups， and the symptoms of atrial flutter were alleviated； HWI （except for arbutin medium-dose group）， LVWI， the levels of CK， LDH， NT-proBNP， Col Ⅰ and Col Ⅲ in the myocardial tissue of rats were decreased significantly （
P
＜0.05）； the degree of myocardial fibrosis in rats decreased； protein and mRNA expressions of ADA and ADK in the myocardial tissue were significantly increased （
P
＜0.05）.
CONCLUSIONS
2
Arbutin can improve cardiac fibrosis and cardiac function of MF model rats， the mechanism of which may be associated with up-regulating protein and mRNA expressions of ADA and ADK， influencing the nucleotide metabolism and collagen generation.
关键词
熊果苷心肌纤维化网络药理学腺苷脱氨酶腺苷激酶
Keywords
myocardial fibrosisnetwork pharma-cologyadenosine deaminaseadenosine kinase
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