Ouyang Yi, Hu Shaowei, Chang Mengli, Xu Jing, Tian Guanghuan, Kong Xixian, Liu Jingtong, Zhang Dong, Zhang Fangbo, Yang Hongjun, Tang Liying, Wu Hongwei
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, PR China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, PR China; Zunyi Medical University, Zunyi, PR China.
Phytomedicine. 2024 Sep;132:155697. doi: 10.1016/j.phymed.2024.155697. Epub 2024 May 7.
Myocardial injury (MI) after acute ischemic stroke (AIS) poses a significant threat to patient prognosis. However, effective intervention strategies are currently lacking.
To elucidate the mechanism of MI after AIS and effects of Naoxintong capsule (NXT) therapy.
In vivo, after a rat model of middle cerebral artery occlusion (MCAO)-induced MI was established and assessed. NXT was administered prophylactically to evaluate its pharmacodynamic effects and mechanisms. In vitro, a noradrenaline (NA)-induced damage cell model was constructed. Subsequently, the NXT was applied to the cell models to examine its cardioprotective effects and potential mechanisms.
The in vivo findings revealed that following MCAO, there was a notable upregulation of TH expression in the rat brain, which subsequently triggered an increase in serum levels of various biomarkers, including AD, NA, AST, cTnT, CK-MB, and NT-proBNP. Histological analysis employing H&E staining and TUNEL assay disclosed significant pathological alterations and an escalation in apoptotic activity within the myocardial tissue. The myocardial tissue exhibited elevated levels of MDA alongside diminished CAT activity. Additionally, a marked increase in the Bax/Bcl-2 ratio, Cytochrome C release, and Caspase-3 activation was observed, all of which are indicative of heightened apoptotic activity. Administration of the NXT intervention successfully attenuated TH expression in the brains of rats subjected to MCAO, consequently leading to a reduction in circulating levels of catecholamines (CAs). NXT also exhibited significant efficacy at ameliorating cardiac oxidative stress and reducing apoptosis. In vitro, stimulation with NA led to an increase in ROS levels and calcium ion concentration in H9c2 cardiomyocytes. However, the administration of NXT has been found to effectively alleviate these adverse effects, thereby protecting H9c2 cardiomyocytes from the deleterious consequences of oxidative stress and calcium dyshomeostasis.
Overall, this study has demonstrated that increased CAs synthesis in the brain after AIS in experimental rats led to a surge in circulating CAs, ultimately leading to MI. NXT can alleviate MI due to cerebral ischemia by increasing improving brain catecholamine synthesis, cardiac oxidative stress, and apoptosis.
急性缺血性卒中（AIS）后的心肌损伤（MI）对患者预后构成重大威胁。然而，目前缺乏有效的干预策略。
阐明AIS后MI的机制及脑心通胶囊（NXT）治疗的效果。
在体内，建立并评估大鼠大脑中动脉闭塞（MCAO）诱导的MI模型。预防性给予NXT以评估其药效学作用和机制。在体外，构建去甲肾上腺素（NA）诱导的损伤细胞模型。随后，将NXT应用于细胞模型以检查其心脏保护作用和潜在机制。
体内研究结果显示，MCAO后，大鼠脑中TH表达显著上调，随后导致包括AD、NA、AST、cTnT、CK-MB和NT-proBNP在内的各种生物标志物血清水平升高。采用苏木精-伊红（H&E）染色和TUNEL检测的组织学分析揭示了心肌组织中显著的病理改变和凋亡活性的增加。心肌组织中MDA水平升高，CAT活性降低。此外，观察到Bax/Bcl-2比值、细胞色素C释放和半胱天冬酶-3激活显著增加，所有这些均表明凋亡活性增强。给予NXT干预成功减弱了MCAO大鼠脑中的TH表达，从而导致循环儿茶酚胺（CAs）水平降低。NXT在改善心脏氧化应激和减少凋亡方面也表现出显著疗效。在体外，NA刺激导致H9c2心肌细胞中ROS水平和钙离子浓度增加。然而，已发现给予NXT可有效减轻这些不良反应，从而保护H9c2心肌细胞免受氧化应激和钙稳态失调的有害影响。
总体而言，本研究表明，实验大鼠AIS后脑内CAs合成增加导致循环CAs激增，最终导致MI。NXT可通过改善脑儿茶酚胺合成、心脏氧化应激和凋亡来减轻脑缺血所致的MI。
