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匝迪-5味丸改善心肌缺血再灌注损伤的作用机制预测及验证
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| 篇名： | 匝迪-5味丸改善心肌缺血再灌注损伤的作用机制预测及验证 |
| TITLE： | Prediction and validation of the mechanism of Zadi-5 pill in protecting myocardial ischemia-reperfusion injury |
| 摘要： | 目的 探讨匝迪-5味丸改善心肌缺血再灌注损伤（MIRI）的作用机制。方法通过网络药理学方法筛选匝迪-5味丸改善MIRI的潜在作用靶点和通路。将72只大鼠随机分为模型组、假手术组、丹参组[复方丹参滴丸80mg/（kg·d）]和匝迪-5味丸高、中、低剂量组[1.6、0.8、0.4g/（kg·d）]，每组12只。各组大鼠灌胃相应药物，每天1次，连续14d。末次给药后，结扎大鼠左冠状动脉前降支建立MIRI模型，假手术组大鼠只穿线不结扎。检测建模后各组大鼠血清中肌酸激酶（CK）、乳酸脱氢酶（LDH）、天冬氨酸转氨酶（AST）、心肌肌钙蛋白T（CTn-T）的含量，心肌细胞凋亡率，心肌组织中磷脂酰肌醇3-激酶（PI3K）、蛋白激酶B（Akt）、B淋巴细胞瘤2（Bcl-2）及Bcl-2相关X蛋白（Bax）、胱天蛋白酶3（caspase-3）蛋白表达水平；观察心肌组织形态变化。结果共获得匝迪-5味丸的活性成分177个，作用靶点220个，参与改善心肌缺血相关的靶点51个，其中核心靶点为AKT1，涉及PI3K-Akt、内质网、缺氧诱导因子-1等多个通路。与模型组比较，丹参组和匝迪-5味丸高剂量组大鼠血清中CK、LDH、AST、CTn-T含量和心肌细胞凋亡率，以及心肌组织中caspase-3、Bax蛋白表达水平均显著降低（P＜0.05或P＜0.01），心肌组织中PI3K、Akt、Bcl-2蛋白表达水平均显著升高（P＜0.05或P＜0.01），心肌组织病理形态改变均明显改善；匝迪-5味丸低、中剂量组大鼠上述指标亦有不同程度改善。结论匝迪-5味丸可能通过激活PI3K-Akt信号通路抑制细胞凋亡，从而发挥改善MIRI的作用。 |
| ABSTRACT： | OBJECTIVE To explore the mechanism of Zadi-5 pill in improving myocardial ischemia-reperfusion injury （MIRI）. METHODS The targets and pathways of potential effects of Zadi-5 pill improving MIRI were screened based on the network pharmacology. Seventy-two rats were randomly divided into model group， sham operation group， Danshen group [Compound danshen dripping pills 80 mg/（kg·d）] and Zadi-5 pill high-dose， medium-dose and low-dose groups [1.6， 0.8， 0.4 g/（kg·d）]， with 12 rats in each group. The rats in each group were given corresponding drugs intragastrically， once a day， for 14 consecutive days. After the last administration， MIRI model was established by ligating the anterior descending branch of left coronary artery in rats， while rats in the sham operation group were threaded without ligation. The contents of creatine kinase （CK）， lactate dehydrogenase （LDH）， aspartate transaminase （AST）， cardiac troponin T （CTn-T）， apoptotic rate of cardiomyocyte， phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， B-cell lymphoma-2 （Bcl-2）， Bcl-2 related X protein （Bax） and caspase-3 in myocardial tissue were detected in each group after modeling； the morphological changes of myocardial tissue were observed. RESULTS A total of 177 active ingredients and 220 targets of Zadi-5 pill were obtained， including 51 targets involved in improving myocardial ischemia； the core target of Zadi-5 pill improving MIRI was AKT1， including PI3K-Akt， endoplasmic reticulum and hypoxia-inducible factor-1. Compared with model group， the contents of CK， LDH， AST and CTn-T， the apoptotic rate of cardiomyocyte as well as the protein expressions of caspase-3 and Bax were significantly decreased in Danshen group and Zadi-5 pill high-dose group （P＜0.05 or P＜0.01）， while the protein expressions of PI3K， Akt and Bcl-2 in myocardial tissue were significantly increased （P＜0.05 or P＜0.01）， respectively； the myocardial histopathological changes were significantly improved. The above indicators were improved to varying degrees in Zadi-5 pill low-dose and medium-dose groups， too. CONCLUSIONS Zadi-5 pill may inhibit apoptosis by activating the PI3K-Akt signaling pathway， thus playing a role in improving MIRI. |
| 期刊： | 2024年第35卷第04期 |
| 作者： | 乌日嘎；威力斯；乌日拉嘎；苏斯；阿茹罕；佟立军；布图雅；呼日乐巴根 |
| AUTHORS： | Wuriga，Weilisi，Wurilaga，Susi，Aruhan，TONG Lijun，Butuya，Hurilebagen |
| 关键字： | 匝迪-5味丸；心肌缺血再灌注损伤；作用机制；磷脂酰肌醇3-激酶/蛋白激酶B信号通路；凋亡 |
| KEYWORDS： | Zadi-5 pill； myocardial ischemic-reperfusion |
| 阅读数： | 9 次 |
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