附子对异丙肾上腺素诱导的大鼠心肌梗死的心脏保护作用。
Cardioprotective Effects of Aconite in Isoproterenol-Induced Myocardial Infarction in Rats.
机构信息
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
National Engineering Research Center for Marine Aquaculture, Institute of Innovation & Application, Zhejiang Ocean University, Zhoushan, China.
出版信息
Oxid Med Cell Longev. 2022 Dec 26;2022:1090893. doi: 10.1155/2022/1090893. eCollection 2022.
BACKGROUND
Myocardial infarction (MI) is a severe clinical condition caused by decreased or complete cessation of blood flow to a portion of the myocardium. Aconite, the lateral roots of Debx., is a well-known Chinese medicine for treatment of heart failure and related cardiac diseases. The present study is aimed at investigating the cardioprotective effect of aconite on isoproterenol- (ISO)- induced MI.
METHODS
The qualitative analysis of aqueous extracts from brained aconite (AEBA) was conducted by HPLC. A rat model of MI induced by ISO was established to examine the effects of AEBA. The cardiac function was assessed by echocardiography. The serum levels of SOD, CK-MB, cTnT, and cTnI were detected to estimate myocardial injury. The pathological changes of heart tissue were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and Masson's trichrome staining. The expressions of abnormal vascular remodeling and hypoxia-related components and the levels of inflammation-associated genes and proteins were detected by RT-qPCR, western blotting, and immunofluorescence.
RESULTS
The contents of benzoylaconine, benzoylmesaconine, benzoylhypacoitine, and hypaconitine in AEBA were 1.35 g/g, 37.35 g/g, 57.10 g/g, and 2.46 g/g, respectively. AEBA obviously improved heart function through promoting echocardiographic parameters, radial strain, and circumferential strain. The data of TTC staining, HE staining, and Masson's trichrome staining disclosed that AEBA could significantly reduce infarct size, inhibit inflammatory cell infiltration, and decrease the myocardial fibrosis. Moreover, AEBA distinctly suppressed the serum levels of SOD, MDA, CK-MB, cTnT, and cTnI in ISO-induced rats. The results of RT-qPCR indicated that AEBA inhibited the expressions of hypoxia- and inflammation-related genes, including VEGF, PKM2, GLUT-1, LDHA, TNF-, IL-1, IL-6, and COX2. In addition, the western blotting and immunofluorescence analyses further confirmed the results of RT-qPCR.
CONCLUSION
In summary, our results indicate that the AEBA could improve ISO-induced myocardial infarction by promoting cardiac function, alleviating myocardial hypoxia, and inhibiting inflammatory response and fibrosis in heart tissue.
背景
心肌梗死（MI）是一种严重的临床病症，由心肌部分血流减少或完全停止引起。乌头是一种著名的中药，用于治疗心力衰竭和相关的心脏疾病。本研究旨在探讨乌头对异丙肾上腺素（ISO）诱导的心肌梗死的心脏保护作用。
方法
采用高效液相色谱法对脑乌头水提物（AEBA）进行定性分析。建立 ISO 诱导的大鼠心肌梗死模型，观察 AEBA 的作用。通过超声心动图评估心功能。检测血清中超氧化物歧化酶（SOD）、肌酸激酶同工酶-MB（CK-MB）、肌钙蛋白 T（cTnT）和肌钙蛋白 I（cTnI）水平，以评估心肌损伤。通过 2,3,5-三苯基氯化四氮唑（TTC）染色、苏木精-伊红（HE）染色和 Masson 三色染色评估心脏组织的病理变化。通过 RT-qPCR、western blot 和免疫荧光检测异常血管重塑和缺氧相关成分的表达以及炎症相关基因和蛋白的水平。
结果
AEBA 中苯甲酰乌头碱、苯甲酰新乌头碱、苯甲酰次乌头碱和次乌头碱的含量分别为 1.35g/g、37.35g/g、57.10g/g和 2.46g/g。AEBA 通过促进超声心动图参数、径向应变和周向应变明显改善心功能。TTC 染色、HE 染色和 Masson 三色染色结果显示，AEBA 可显著减少梗死面积，抑制炎性细胞浸润，减少心肌纤维化。此外，AEBA 明显抑制 ISO 诱导大鼠血清中 SOD、MDA、CK-MB、cTnT 和 cTnI 的水平。RT-qPCR 结果表明，AEBA 抑制了缺氧和炎症相关基因的表达，包括 VEGF、PKM2、GLUT-1、LDHA、TNF-α、IL-1、IL-6 和 COX2。此外，western blot 和免疫荧光分析进一步证实了 RT-qPCR 的结果。
结论
综上所述，我们的研究结果表明，AEBA 通过促进心功能、减轻心肌缺氧、抑制心肌组织炎症反应和纤维化，改善 ISO 诱导的心肌梗死。
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