重楼皂苷I预防给药对心肌缺血再灌注损伤大鼠调节PI3K/AKT信号通路的作用研究
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陕西省自然科学基础研究计划一般项目(面上)(2022JM-488)


Polyphyllin I regulate the rats with myocardial ischemia-reperfusion injury by PI3K/AKT signaling pathway
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    摘要:

    目的 从磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)信号通路探讨重楼皂苷I预防给药对心肌缺血再灌注损伤(MI/IR)大鼠的干预机制。方法 将购买的72只SPF级SD大鼠按照随机数字法分为假手术组、模型组、阿司匹林组、重楼皂苷I低、中和高剂量组,每组12只。分组后即给予相应药物干预2周,2周后构建MI/IR模型。模型构建成功24 h后先采用动物彩色多普勒超声仪检测心脏功能,后处死大鼠收集相关组织采用HE染色观察心肌病理学、TTC法检测心肌梗死面积,试剂盒检测心功能指标[乳酸脱氢酶(LDH)、肌酸激酶同工酶MB(CK-MB)和谷草转氨酶(AST),抗氧化指标丙二醛(MDA)、超氧化物歧化酶(SOD)和谷胱甘肽(GSH)],TUNNEL染色检测心肌细胞凋亡特点,Western blot检测心肌PI3K、AKT、B细胞淋巴瘤/因子2(Bcl-2)、Bcl-2 相关蛋白(Bax)蛋白表达。结果 假手术组心肌纤维排列整齐、无水肿,模型组有心肌纤维断裂,重楼皂苷I低、中、高剂量组和阿司匹林组明显改善心肌纤维断裂情况。与假手术组相比,模型组大鼠心肌梗死面积、LVEDP、LDH、CK-MB、AST和MDA明显升高(P<0.05),LVDP、+dp/dtmax、-dp/dtmax、SOD和GSH明显降低(P<0.05);相较于模型组,阿司匹林组和重楼皂苷I低、中、高剂量组干预后,心肌梗死面积、LVEDP、LDH、CK-MB、AST和MDA明显降低(P<0.05),LVDP、+dp/dtmax、-dp/dtmax、SOD和GSH则明显升高(P<0.05)。Tunnel染色可见,假手术组几乎没有心肌细胞凋亡,而模型组呈现出明显的大量的细胞凋亡;与模型组相比,阿司匹林组和重〖JP2〗楼皂苷I低、中、高剂量组凋亡情况明显好转。此外,与假手术组相比,模型组大鼠心肌PI3K、AKT和Bcl-2蛋白表达均明显降低,Bax明显升高(均P<0.05);相较于模型组,重楼皂苷I低、中、高剂量组以及阿司匹林组PI3K、AKT和Bcl-2蛋白表达均明显升高,Bax蛋白表达明显降低(均P<0.05)。结论 重楼皂苷I对心肌缺血再灌注损伤有一定的预防作用,其作用机理可能与其能够调节PI3K/AKT信号通路有关

    Abstract:

    Objective To explore the intervention mechanism of myocardial ischemia/reperfusion injury (MI/IR) rats model from PI3K/AKT signaling pathway by preventive administration of polyphyllin I. Methods A total of 72 purchased clean-grade (SPF) SD rats were randomly divided into sham operation, model, aspirin, Polyphyllin I low-dose, medium-dose and high-dose groups(n=12), and the corresponding drug intervention was given for 2 weeks immediately after grouping, and the MI/IR model was constructed after 2 weeks of administration. After 24 h of successful model construction, cardiac function was first measured by color Doppler ultrasonography, then the rats were executed and the relevant tissues were collected by HE staining to observe myocardial pathology. TTC method was to detect myocardial infarction area. The kits were used to detect cardiac function indicators lactate dehydrogenase (LDH), creatine kinase isoenzyme MB (CK-MB) and glutathione transaminase (AST), antioxidant indicators malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH). The expression of myocardial phosphatidylinositol-3-kinase (PI3K), protein kinase B (AKT), B-cell lymphoma/factor 2 (Bcl-2) and Bcl-2-associated protein (Bax) were measured by Western blotting. Results The sham-operated group had neatly arranged myocardial fibers without edema, and the model group had myocardial fiber breaks. Myocardial fiber breakage was significantly improved in the three treatment groups of polyphyllin I and aspirin. Compared with sham operation group, the myocardial infarction area, LVEDP, LDH, CK-MB, AST and MDA were significantly increased in model group (P<0.05), while LVDP, +dp/dtmax, -dp/dtmax, SOD and GSH were significantly decreased in model group (P<0.05). Compared with model group, after aspirin and Polyphyllin I intervention, the myocardial infarction area, LVEDP, LDH, CK-MB, AST and MDA were significantly decreased (P<0.05), while LVDP, +dp/dtmax, -dp/dtmax, SOD and GSH were significantly increased (P<0.05). Tunnel staining showed that there was almost no myocardial apoptosis in the sham group, while in the model group showed a significant amount of apoptosis. Compared with the model group, the apoptosis was significantly improved in the aspirin group and the three Polyphyllin I groups. In addition, compared with sham operation group, the protein expressions of PI3K, Akt and Bcl-2 in model group were significantly decreased (P<0.05), while Bax was significantly increased (P<0.05). Compared with model group, the protein expressions of PI3K, Akt and Bcl-2 in the three dose Polyphyllin I groups and aspirin group were significantly increased (P<0.05), while the Bax protein expression was significantly decreased (P<0.05).Conclusion Polyphyllin I has a certain preventive effect on myocardial ischemia-reperfusion injury, and its mechanism may be related to its regulation of PI3K/AKT signaling pathway

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  • 在线发布日期: 2024-03-20
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