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紫云英苷通过阻断 HMGB1 依赖的 NF-κB 信号通路保护糖尿病大鼠心脏免受缺血再灌注损伤。

Astilbin protects diabetic rat heart against ischemia-reperfusion injury via blockade of HMGB1-dependent NF-κB signaling pathway.

机构信息

School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, PR China.

School of Pharmaceutical Sciences, Binzhou Medical University, Yantai 264003, PR China.

出版信息

Food Chem Toxicol. 2014 Jan;63:104-10. doi: 10.1016/j.fct.2013.10.045. Epub 2013 Nov 6.

Abstract

Astilbin, a flavonoid compound was isolated from the rhizome of Smilax china L. In this study, we investigated the anti-myocardial ischemia and reperfusion (I/R) injury effect of Astilbin on diabetic rats in vivo and elucidated the potential mechanism in vitro. The results showed that Astilbin significantly attenuated hypoxia-induced cell injury in a concentration-dependent manner. Treatment of H9c2 cells with Astilbin at 15 μM blocked nuclear factor kappaB (NF-κB) phosphorylation by blocking High-mobility group box protein 1 (HMGB1) expression. Treatment of diabetic rats with Astilbin by intravenous injection (i.v.) at a single dose of 50 mg/kg protected the rats from myocardial I/R injury as indicated by decreasing infarct volume, improving hemodynamics and reducing myocardial damage, and also lowered serum levels of pro-inflammatory factors, reduced HMGB1 and phosphorylated NF-κB expression in ischemic myocardial tissue from diabetic rats. Additionally, treatment of diabetic rats with Astilbin at dose of 50 mg/kg by i.v. for continuous 14 days attenuated cardiac remodeling in the model myocardial I/R injury. These protective effects suggested that Astilbin might be due to block of the myocardial inflammatory cascade via the HMGB1-dependent NF-κB signaling pathway.

摘要

朝藿定 B 是从菝葜属植物中分离得到的一种黄酮类化合物。本研究旨在探讨朝藿定 B 对糖尿病大鼠体内心肌缺血再灌注(I/R)损伤的保护作用及其潜在机制。结果表明,朝藿定 B 可显著减轻缺氧诱导的细胞损伤,呈浓度依赖性。15μM 朝藿定 B 处理 H9c2 细胞可通过抑制高迁移率族蛋白 B1(HMGB1)表达来阻断核因子 κB(NF-κB)磷酸化。单次静脉注射 50mg/kg 朝藿定 B 可减轻糖尿病大鼠心肌 I/R 损伤,表现为梗死面积减小、血流动力学改善和心肌损伤减轻,同时降低血清促炎因子水平,减少缺血性心肌组织中 HMGB1 和磷酸化 NF-κB 的表达。此外,连续静脉注射 50mg/kg 朝藿定 B 14 天可减轻模型心肌 I/R 损伤中的心脏重构。这些保护作用表明,朝藿定 B 可能通过 HMGB1 依赖的 NF-κB 信号通路阻断心肌炎症级联反应。

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