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清热活血汤改善大鼠心肌缺血再灌注损伤的药效成分及作用机制研究
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| 篇名： | 清热活血汤改善大鼠心肌缺血再灌注损伤的药效成分及作用机制研究 |
| TITLE： | Study on pharmacological components and mechanism of Qingre huoxue decoction in improving myocardial ischemia-reperfusion injury |
| 摘要： | 目的 探讨清热活血汤改善大鼠心肌缺血再灌注损伤（MIRI）的药效成分及作用机制。方法将42只大鼠随机分为假手术组（生理盐水），模型组（生理盐水），清热活血汤低、中、高剂量组（4.94、9.88、19.79g/kg），清热活血汤含药血清组（19.79g/kg），空白血清组（生理盐水），每组6只。各组大鼠灌胃相应药物/生理盐水，每天1次，连续2周。末次给药12h后，除各血清组外，其余各组大鼠进行MIRI造模（假手术组仅穿线不结扎），并在造模成功后，进行心脏组织病理学形态观察及细胞凋亡水平检测。取清热活血汤含药血清组、空白血清组样本进行超高效液相色谱质谱联用（UPLC-MS）分析，结合相关数据库筛选清热活血汤含药血清中的主要药效成分，结合多元统计学方法分析其差异代谢物及相关代谢通路，并基于氧化应激指标进行实验验证。结果清热活血汤可改善MIRI模型大鼠心脏组织病理损伤，显著降低细胞凋亡率（P＜0.05）。清热活血汤含药血清包括黄芩苷、琥珀酸、黄芩素、隐丹参酮、异阿魏酸、原儿茶醛等20种主要药效成分，可上调L-异亮氨酸、左旋精氨酸、柠檬酸、谷胱甘肽、β-D-葡萄糖、左旋肉碱等15种代谢物水平（P＜0.05），下调花生四烯酸、3-磷酸-d-甘油磷酸酯、亚油酸、二十二碳六烯酸、磷脂酰胆碱、溶血磷脂酰胆碱等14种代谢物水平（P＜0.05），主要涉及能量代谢、炎症损伤、氧化应激和自噬等代谢途径。验证实验结果显示，清热活血汤可显著降低MIRI模型大鼠血清中丙二醛水平，显著升高超氧化物歧化酶（低剂量组除外）及谷胱甘肽过氧化物酶水平（P＜0.05）。结论清热活血汤可改善MIRI模型大鼠心脏组织损伤，其药效成分包括黄芩苷、隐丹参酮、异阿魏酸、原儿茶醛等，其作用机制可能与改善心肌能量代谢、下调氧化应激水平、抑制炎症浸润有关。 |
| ABSTRACT： | OBJECTIVE To investigate the pharmacological components and mechanism of Qingre huoxue decoction in improving myocardial ischemia-reperfusion injury（MIRI）. METHODS Forty-two rats were randomly divided into sham operation group （normal saline）， model group （normal saline）， Qingre huoxue decoction low-dose， medium-dose and high-dose groups （4.94， 9.88， 19.79 g/kg），Qingre huoxue decoction drug-containing serum group （19.79 g/kg） and blank serum group （normal saline）， with 6 rats in each group. Each group was given corresponding drug/normal saline intragastrically， once a day， for consecutive 2 weeks. Twelve hours after last administration， except for serum groups， MIRI model was induced in other groups （only threading without ligation in sham operation group）. After modeling， cardiac histopathology was observed and apoptosis level was detected. UPLC-MS was used to analyze the samples in Qingre huoxue decoction drug-containing serum group and blank serum group. The main pharmacological components were screened with the help of relevant databases. Multivariate statistical methods were used to analyze the differential metabolites and related metabolic pathways. Validation test was performed based on oxidative stress indicators. RESULTS Qingre huoxue decoction could improve the pathological injury of cardiac tissue and decrease apoptosis rate of cardiac cells in MIRI model rats （P＜0.05）. Qingre huoxue decoction drug-containing serum contained 20 main pharmacological components such as baicalin， succinic acid， baicalein， cryptotanshinone， isoferulic acid， protocatechuic aldehyde. Qingre huoxue decoction could significantly up-regulate the levels of 15 metabolites including L-arginine， L-arginine， citric acid， glutathione， β-D- glucose and L-carnitine， and down-regulated the levels of 14 metabolites including arachidonic acid， 3-phosphate-d-glycerol phosphate， linoleic acid， docosahexaenoic acid， phosphatidylcholine and lysophosphatidylcholine （P＜0.05）. These metabolites were mainly involved in energy metabolism， inflammatory injury， oxidative stress and autophagy. Results of validation tests showed that Qingre huoxue decoction could significantly reduce the levels of malondialdehyde， and increased the levels of superoxide dismutase （except for low-dose group） and glutathione peroxidase significantly （P＜0.05）. CONCLUSIONS Qingre huoxue decoction can improve the injury of cardiac tissue in MIRI model rats. Its pharmacological components include baicalin， cryptotanshinone， isoferulic acid， protocatechualdehyde， etc. Furthermore， it may play a protective role in MIRI by improving myocardial energy metabolism， down-regulating oxidative stress， inhibiting inflammation infiltration. |
| 期刊： | 2022年第33卷第23期 |
| 作者： | 李睿，纪树亮，章洁淳，孙治中，杨晓丹，刘煜德，邝枣园，卿立金，吴伟 |
| AUTHORS： | LI Rui，JI Shuliang， ZHANG Jiechun，SUN Zhizhong，YANG Xiaodan，LIU Yude，KUANG Zaoyuan，QING Lijin，WU Wei |
| 关键字： | 清热活血汤；心肌缺血再灌注损伤；药效成分；机制 |
| KEYWORDS： | Qingre huoxue decoction； myocardial ischemia-reperfusion injury； pharmacological components； mechanism |
| 阅读数： | 216 次 |
| 本月下载数： | 5 次 |
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