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Scutellarin Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Myocardial Fibrosis, Apoptosis and Autophagy in Rats
Chemistry & Biodiversity ( IF 2.9 ) Pub Date : 2022-11-23 , DOI: 10.1002/cbdv.202200450
Xipeng Sun 1 , Li Zhou 1, 2 , Yonglong Han 1 , Quanjun Yang 1 , Xingxia Li 1 , Bo Xin 1 , Mengyi Chi 1 , Yaxian Wang 1 , Cheng Guo 1
Affiliation  

The anthracycline antibiotic doxorubicin (DOX) is an effective anticancer agent, but its clinical use is limited by dose-dependent cardiotoxicity. Scutellarin (SCU), a natural polyphenolic flavonoid, is used as a cardioprotective agent for infarction and ischemia-reperfusion injury. This study investigated the beneficial effect of SCU on DOX-induced chronic cardiotoxicity. Rats were injected intraperitoneally (i. p.) with DOX (2.5 mg/kg) twice a week for four weeks and then allowed to rest for two weeks to establish the chronic cardiotoxicity animal model. A dose of 10 mg/kg/day SCU was injected i. p. daily for six weeks to attenuate cardiotoxicity. SCU attenuated DOX-induced elevated oxidative stress levels and cardiac troponin T (cTnT), decreased left ventricular ejection fraction (LVEF) and fractional shortening (LVFS), elevated isovolumic relaxation time (IVRT), electrophysiology and histopathological alterations. In addition, SCU significantly attenuated DOX-induced cardiac fibrosis and reduced extracellular matrix (ECM) accumulation by inhibiting the TGF-β1/Smad2 signaling pathway. Furthermore, SCU also prevented against DOX-induced apoptosis and autophagy as evidenced by upregulation of Bcl-2, downregulation of Bax and cleaved caspase-3, inhibited the AMPK/mTOR pathway. These results revealed that the cardioprotective effect of SCU on DOX-induced chronic cardiotoxicity may be attributed to reducing oxidative stress, myocardial fibrosis, apoptosis and autophagy.

中文翻译:

灯盏花乙素通过抑制大鼠心肌纤维化、细胞凋亡和自噬减轻多柔比星诱导的心脏毒性

蒽环类抗生素多柔比星 (DOX) 是一种有效的抗癌剂,但其临床应用受到剂量依赖性心脏毒性的限制。灯盏花乙素 (SCU) 是一种天然多酚类黄酮,用作梗塞和缺血再灌注损伤的心脏保护剂。本研究调查了 SCU 对 DOX 诱导的慢性心脏毒性的有益作用。大鼠腹腔注射DOX (2.5 mg/kg),每周两次,持续 4 周,然后静置两周,建立慢性心脏毒性动物模型。腹腔注射 10 mg/kg/天 SCU 的剂量。p. 每天服用六周,以减轻心脏毒性。SCU 减弱了 DOX 引起的升高的氧化应激水平和心肌肌钙蛋白 T (cTnT)、降低的左心室射血分数 (LVEF) 和缩短分数 (LVFS)、升高的等容舒张时间 (IVRT)、电生理学和组织病理学改变。此外,SCU 通过抑制 TGF-β1/Smad2 信号通路显着减轻 DOX 诱导的心脏纤维化并减少细胞外基质 (ECM) 的积累。此外,SCU 还可以防止 DOX 诱导的细胞凋亡和自噬,这可以通过上调 Bcl-2、下调 Bax 和裂解的 caspase-3、抑制 AMPK/mTOR 通路来证明。这些结果表明,SCU 对 DOX 诱导的慢性心脏毒性的心脏保护作用可能归因于减少氧化应激、心肌纤维化、
更新日期:2022-11-23
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