Effect of Schisandrin B on acute myocardial ischemic injury in rats based on thioredoxin interaction protein /thioredoxin/apoptosis signal-regulating kinase 1 pathway
WANG Yuan LIU Shengnan HAO Na JIANG Hong LI Liping ZHANG Qinzeng XIE Lijun
Institute of Materia Medica, Hebei Academy of Medical Science, Hebei Province, Shijiazhuang 050021, China
Abstract：Objective To study the effect of Schisandrin B (Sch B) on the expression of thioredoxin interaction protein (TXNIP), thioredoxin (TRX), and apoptosis signal-regulating kinase 1 (ASK1) in acute myocardial ischemic injury of rats. Methods Sixty SPF male SD rats (body weight 210-250 g) were selected and divided into control group, model group, and SchB low-dose, medium-dose, and high-dose groups (20, 40, 80 mg/kg) by random number table method, with 12 rats in each group. SchB low-dose, medium-dose, and high-dose groups were intragastrically given the corresponding drug (10 ml/kg), while control group and model group were intragastrically given 1% sodium carboxymethylcellulose, once a day, for consecutive 14 days. Two hours after the last administration, myocardial ischemia model was establishedby ligation of the left anterior descending branch of coronary artery in the model group and SchB low-dose, medium-dose, high-dose groups, while the control group only underwent thoracotomy without ligation. Mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximum rate of rise or fall of left ventricular pressure (±dp/dtmax), and left ventricular developmental pressure (LVDP) were measured at 3 h of ischemia. Then the rats were killed and the heart tissue was taken. The contents of lipid peroxides (LPO), glutathione (GSH), and the activities of TRX reductase (TrxR) of heart tissues in five groups were determined by enzyme-labeled instrument. TTC staining was used to measure myocardial infarction size. Myocardial cell apoptosis was observed by TUNEL staining. TXNIP, TRX, cysteine aspartic acid specific protease-3 (caspase-3), ASK1, and p-ASK1 levels were detected by Western blot. Results The MAP, LVDP, ±dp/dtmax, expression of GSH, TrxR, and TRX in model group were lower than those in control group, while the LVEDP, LPO, myocardial apoptosis index (AI), and expressions of TXNIP, caspase-3, and p-ASK1/ASK1 in model group were higher than those in control group (P＜0.05). The expression of GSH, TrxR, and TRX in SchB low-dose, medium-dose, and high-dose groups were higher than those in model group, while LPO and myocardial infarction area were lower than those in model group (P＜0.05). MAP, LVDP, ±dp/dtmax in SchB medium-dose and high-dose groups were higher than those in model group, while the LVEDP, myocardial AI, and expressions of TXNIP, caspase-3, and p-ASK1/ ASK1 in SchB medium-dose and high-dose groups were lower than those in model group (P＜0.05). The MAP, LVDP, ±dp/dtmax, and expression of TRX in SchB high-dose group were higher than those in SchB low-dose group, and the LVEDP, myocardial infarction area, myocardial AI, and expressions of TXNIP, caspase-3, p-ASK1/ASK1 in SchB high-dose group were lower than those in SchB low-dose group (P＜0.05). Conclusion SchB may play a myocardial protective role by reducing oxidative stress injury and inhibiting myocardial apoptosis through TXNIP/TRX/ASK1 pathway.
王媛 刘晟楠 郝娜 姜红 李立萍 张勤增 解丽君. 五味子乙素基于硫氧还蛋白互作蛋白/硫氧还蛋白/凋亡信号调节激酶1通路对大鼠急性心肌缺血损伤的影响[J]. 中国医药导报, 2023, 20(10): 23-27,41.
WANG Yuan LIU Shengnan HAO Na JIANG Hong LI Liping ZHANG Qinzeng XIE Lijun. Effect of Schisandrin B on acute myocardial ischemic injury in rats based on thioredoxin interaction protein /thioredoxin/apoptosis signal-regulating kinase 1 pathway. 中国医药导报, 2023, 20(10): 23-27,41.
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