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黄芪甲苷通过调节 Toll 样受体 4/核因子-κB 信号通路减轻大鼠心肌缺血再灌注损伤。

Astragaloside IV attenuates injury caused by myocardial ischemia/reperfusion in rats via regulation of toll-like receptor 4/nuclear factor-κB signaling pathway.

机构信息

Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Liaoning Medical University, Jinzhou, 121001, PR China.

出版信息

Phytother Res. 2015 Apr;29(4):599-606. doi: 10.1002/ptr.5297. Epub 2015 Jan 21.

Abstract

Myocardial ischemia/reperfusion (MI/R) injury, in which inflammatory response and cell apoptosis play a vital role, is frequently encountered in clinical practice. Astragaloside IV (AsIV), a small molecular saponin of Astragalus membranaceus, has been shown to confer protective effects against many cardiovascular diseases. The present study was aimed to investigate the antiinflammatory and antiapoptotic effects and the possible mechanism of AsIV on MI/R injury in rats. Rats were randomly divided into sham operation group, MI/R group and groups with combinations of MI/R and different doses of AsIV. The results showed that the expressions of myocardial toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) were significantly increased, and apoptosis of cardiomyocytes was induced in MI/R group compared with that in sham operation group. Administration of AsIV attenuated MI/R injury, downregulated the expressions of TLR4 and NF-κB and inhibited cell apoptosis as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells, B-cell lymphoma-2 associated X protein and caspase-3 expressions and increased B-cell lymphoma-2 expression compared with that in MI/R group. In addition, AsIV treatment reduced levels of inflammatory cytokines induced by MI/R injury. In conclusion, our results demonstrated that AsIV downregulates TLR4/NF-κB signaling pathway and inhibits cell apoptosis, subsequently attenuating MI/R injury in rats.

摘要

心肌缺血/再灌注(MI/R)损伤,其中炎症反应和细胞凋亡起着至关重要的作用,在临床上经常遇到。黄芪甲苷(AsIV)是黄芪的一种小分子皂甙,已被证明对许多心血管疾病具有保护作用。本研究旨在探讨 AsIV 对大鼠 MI/R 损伤的抗炎和抗凋亡作用及可能的机制。大鼠随机分为假手术组、MI/R 组和 MI/R 与不同剂量 AsIV 组合组。结果显示,与假手术组相比,MI/R 组心肌 toll 样受体 4(TLR4)和核因子-κB(NF-κB)的表达明显增加,诱导心肌细胞凋亡。AsIV 给药减轻了 MI/R 损伤,下调了 TLR4 和 NF-κB 的表达,并抑制了细胞凋亡,这表现在末端脱氧核苷酸转移酶 dUTP 缺口末端标记阳性细胞、B 细胞淋巴瘤-2 相关 X 蛋白和半胱天冬酶-3 的表达减少,B 细胞淋巴瘤-2 的表达增加,与 MI/R 组相比。此外,AsIV 治疗降低了由 MI/R 损伤引起的炎症细胞因子的水平。总之,我们的结果表明,AsIV 下调 TLR4/NF-κB 信号通路并抑制细胞凋亡,从而减轻大鼠的 MI/R 损伤。

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