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西藏民族大学医学院,西藏民族大学藏药检测技术教育部工程研究中心,陕西 咸阳 712082
ZHANG XiaoYing, E-mail:xyzhang@xzmu.edu.cn
Received:11 July 2026,
Revised:2026-08-03,
Accepted:24 August 2026,
Online First:25 August 2026,
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ZHANG Xiaoying, XIE yuquan, ZHANG yuchan, et al. Bawei Chenxiang Wan Protects Against Acute Myocardial Ischemia by Activating PI3K to Inhibit Cuproptosis in Rats[J/OL]. Journal of Sun Yat-sen University(Medical Sciences), 2026, 1-15.
ZHANG Xiaoying, XIE yuquan, ZHANG yuchan, et al. Bawei Chenxiang Wan Protects Against Acute Myocardial Ischemia by Activating PI3K to Inhibit Cuproptosis in Rats[J/OL]. Journal of Sun Yat-sen University(Medical Sciences), 2026, 1-15. DOI: 10.11714/jsysu.med.YX20260105.
目的
2
为了研究藏药八味沉香丸(Bawei Chenxiang Wan,BCW)防治心肌缺血的有效活性部位及机制。
方法
2
建立异丙肾上腺素(isoproterenol,ISO)诱导大鼠在体心肌缺血模型、冠脉结扎离体心脏缺血模型,评估BCW全方、醇提物及其不同极性萃取物对心电图ST段、心肌损伤、血流动力学及心肌梗死的影响。检测心肌组织磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)磷酸化水平、铜死亡相关蛋白的表达,以及Cu²⁺含量。利用氧糖剥夺(oxygen-glucose deprivation,OGD)心肌细胞损伤模型联合PI3K激动剂和抑制剂验证通路调控关系。
结果
2
BCW全方可改善心肌缺血大鼠心电图ST段抬高(
P
<0.01),降低心肌损伤标志物含量,改善血流动力学,上调PI3K磷酸化水平(
P
<0.01),减少Cu²⁺蓄积(
P
<0.01),缩小心肌梗死范围。BCW醇提物及各萃取物可改善离体大鼠离体心肌缺血,减少Cu²⁺蓄积,其中BCW正丁醇萃取物效果较好(
P
<0.01);其可上调PI3K磷酸化水平(
P
<0.01)、下调铁氧还蛋白还原酶(ferredoxin reductase 1, FDX1)(
P
<0.05)、硫辛酸合酶(lipoic acid synthetase, LIAS)、二氢硫辛酰胺乙酰转移酶(dihydrolipoamide S-acetyltransferase, DLAT)多聚体表达(
P
<0.05)。在OGD诱导心肌细胞模型中,PI3K激动剂可抑制DLAT多聚体表达(
P
<0.05),而PI3K抑制剂可削弱正丁醇萃取物对DLAT多聚体的抑制作用(
P
<0.05)。
结论
2
BCW正丁醇萃取物是改善大鼠心肌缺血的主要有效部位,其机制可能与PI3K激活介导的铜死亡抑制有关。
Objective
2
To investigate the protective effect and underlying mechanisms of the Bawei Chenxiang Wan (BCW) against myocardial ischemic injury.
Methods
2
Myocardial ischemia was induced in rats by subcutaneous injection of isoproterenol (ISO), and ex
vivo
ischemia was established by coronary artery ligation in isolated rat hearts.The effects of BCW and its polar extracts on electrocardiogram (ECG), myocardial histopathology, serum cardiac enzymes, hemodynamic parameters, and infarct size were evaluated. The expression of proteins related to the PI3K and cuproptosis (FDX1, LIAS, DLAT) were detected. The levels of Cu²⁺and glutathione in myocardial tissue were measured. In an oxygen-glucose deprivation (OGD) model of H9c2 cardiomyocyte injury, the effects of the n-butanol extract of BCW and the PI3K agonist and inhibitor were examined.
Results
2
BCW ameliorated ST-segment abnormalities on electrocardiograms, reduced serum levels of myocardial injury markers, improved hemodynamic parameters, upregulated PI3K phosphorylation(
P
<0.01), and decreased Cu²⁺ accumulation in rats with myocardial ischemia(
P
<0.01). Moreover, BCW reduced the myocardial infarct size. In the isolated rat heart model of ischemia, both the ethanol extract and various solvent fractions of BCW exerted protective effects and reduced Cu²⁺ content, among which the n-butanol fraction exhibited the most potent activity(
P
<0.01). Specifically, the n-butanol fraction upregulated PI3K phosphorylation(
P
<0.01) and downregulated the expression of cuproptosis-related proteins, including FDX1(
P
<0.05), LIAS, and DLAT oligomerization(
P
<0.05). In the OGD-induced cardiomyocyte injury model, treatment with a PI3K agonist inhibited DLAT oligomerization(
P
<0.05), whereas co-administration of a PI3K inhibitor attenuated the inhibitory effect of the n-butanol fraction on DLAT oligomer formation(
P
<0.05).
Conclusion
2
BCW exerts a significant protective effect against myocardial ischemic injury, and its mechanism may involve activation of the PI3K and inhibition of cuproptosis.
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