文章摘要
冠心宁片改善大鼠心肌焦亡机制探究
Study on the mechanism of Guanxinning tablet improving myocardial pyroptosis in rats
投稿时间:2022-06-28  修订日期:2022-07-05
DOI:
中文关键词: 冠心宁片  心力衰竭  大鼠  阿霉素  心肌细胞焦亡
英文关键词: Guanxinning tablet  Heart failure  Rat  Doxorubicin  Cardiomyocyte pyroptosis
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中文摘要:
      目的:观察冠心宁片(GXN)对阿霉素诱导的大鼠心力衰竭(HF)的治疗作用,并从细胞焦亡的角度探讨其作用机制,为冠心宁片的临床应用提供参考。方法:将大鼠30只随机分为正常对照组、模型对照组、冠心宁片低剂量组(600mg/kg)、冠心宁片高剂量组(600mg/kg)和地高辛组(0.05mg/kg),每组6只,通过多次腹腔注射阿霉素诱导大鼠HF模型,造模的同时开始给药,连续灌胃9周。末次给药后行超声心动图检测心功能指标,血清检测NT-proBNP、IL-1β和IL-18,心脏组织行HE染色,观察心肌病理学形态变化,行Masson染色观察心肌纤维化并测定心肌胶原容积分数(CVF),RT-PCR法检测NF-κB、TXNIP、NLRP3、ASC、Caspase-1、IL-1β和IL-18的mRNA表达。结果:与正常对照组比,模型对照组的IVSd、IVSs、LVPWs、SV、FS、EF和心率显著降低,LVIDs、ESV显著增加,心肌出现明显的病理改变,纤维化增加,NF-κB、TXNIP、NLRP3、ASC、Caspase-1、IL-1β和IL-18的mRNA表达均显著增加。与模型对照组相比,冠心宁片可显著增加IVSs、SV、FS、EF和心率,显著降低LVIDs、ESV,改善心肌病理损伤,减少纤维化,降低心衰大鼠的NF-κB、TXNIP、NLRP3、ASC、Caspase-1、IL-1β和IL-18的mRNA表达。结论 冠心宁片可降低阿霉素对心肌的损伤,增强大鼠的心脏功能,其作用机制可能是通过抑制NLRP3/ASC/Caspase-1通路改善大鼠心肌焦亡。
英文摘要:
      [Abstract] Objective To observe the therapeutic effect of Guanxinning Tablets on doxorubicin-induced heart failure (HF) in rats, and to explore its action pathway from the perspective of cell pyroptosis, so as to provide reference for the clinical application of Guanxinning Tablets. Methods The 30 rats were randomly divided into normal control group, model control group, Guanxinning tablet low-dose group (600 mg/kg), Guanxinning tablet high-dose group (600 mg/kg) and digoxin group (0.05 mg/kg). ), 6 pieces per group, the rat HF model was induced by multiple intraperitoneal injections of doxorubicin, and the drug was administered at the same time as the model was established, and it was continuously administered by gavage for 9 weeks. The survival of the rats was recorded in the experiment. After the last administration, echocardiography was used to detect cardiac function indexes. After the rats were sacrificed, serum was collected to detect NT-proBNP, IL-1β and IL-18, and HE staining was performed on cardiac tissue to observe cardiomyopathy. Physical morphological changes, Masson staining was used to observe myocardial fibrosis and myocardial collagen volume fraction (CVF) was determined, RT-PCR was used to detect the mRNA expression of NF-κB, TXNIP, NLRP3, ASC, Caspase-1, IL-1β and IL-18. Results Compared with the normal control group, the IVSd, IVSs, LVPWs, SV, FS, EFand heart rate of the model control group were significantly reduced, LVIDs and ESV were significantly increased, myocardium showed significant pathological changes, fibrosis increased, and the mRNA expression of NF-κB, TXNIP, NLRP3, ASC, Caspase-1, IL-1β and IL-18 was significantly increased. Compared with the model control group, Guanxinning tablet significantly increased IVSs, SV, FS, EF and heart rate, significantly reduced LVIDs and ESV, improved myocardial pathological damage, reduced fibrosis, and reduced mRNA expression of NF-κB, TXNIP, NLRP3, ASC, Caspase-1, IL-1β and IL-18. Conclusion Guanxinning tablet can reduce doxorubicin damage to myocardium and enhance cardiac function in rats, and its mechanism may be to improve myocardial pyroptosis in rats by inhibiting the NLRP3/ASC/Caspase-1 pathway.
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