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Heat shock protein 70 expression protects against sepsis-associated cardiomyopathy by inhibiting autophagy
Human & Experimental Toxicology ( IF 2.8 ) Pub Date : 2020-10-19 , DOI: 10.1177/0960327120965758
Xiaofeng Wang , Yan Zhu , Qiuxiang Zhou 1 , Yueyue Yan 1 , Jinlong Qu 1 , Hongwei Ye 2
Affiliation  

Objectives:

Increasing evidence suggests that heat shock protein 70 (Hsp70) has a protective effect in sepsis-induced cardiomyopathy; however, the protective mechanism remains unclear.

Methods:

Previous studies have also implicated autophagy in sepsis-induced cardiomyopathy. The aim of the current study was to reveal the protective mechanisms of Hsp70 in sepsis-induced cardiomyopathy using a cecal ligation and puncture (CLP) rat sepsis model. The roles of Hsp70 and autophagy in sepsis-induced cardiomyopathy were investigated by pretreating rats with the Hsp70 inhibitor quercetin or the autophagy inhibitor 3-methyladenine (3-Ma) before CLP. We also investigated the protective mechanisms of Hsp70 and the relationship between Hsp70 and autophagy in vitro by stimulating H9c2 cells with lipopolysaccharide (LPS) to simulate sepsis.

Results:

The result show that inhibition of Hsp70 promoted sepsis-induced death in rats, while inhibition of autophagy inhibited sepsis-induced death. These results suggested that both Hsp70 and autophagy were involved in sepsis-induced cardiomyopathy. Overexpression of Hsp70 in H9c2 myocardial cells in vitro suppressed LPS-induced apoptosis, while inhibition of autophagy with 3-Ma also decreased LPS-induced H9c2 cell apoptosis, suggesting that the protective effect of Hsp70 in sepsis-induced cardiomyopathy was related to autophagy regulation.

Conclusion:

Overall, these results suggested that Hsp70 protected against sepsis-induced cardiac impairment by attenuating sepsis-induced autophagy.



中文翻译:

热休克蛋白 70 表达通过抑制自噬预防脓毒症相关心肌病

目标:

越来越多的证据表明热休克蛋白 70 (Hsp70) 对脓毒症引起的心肌病具有保护作用;然而,保护机制仍不清楚。

方法:

先前的研究也表明自噬与脓毒症引起的心肌病有关。本研究的目的是利用盲肠结扎穿刺(CLP)大鼠脓毒症模型揭示 Hsp70 在脓毒症诱发的心肌病中的保护机制。通过在 CLP 前用 Hsp70 抑制剂槲皮素或自噬抑制剂 3-甲基腺嘌呤 (3-Ma) 预处理大鼠,研究了 Hsp70 和自噬在脓毒症诱发的心肌病中的作用。我们还通过用脂多糖(LPS)刺激H9c2细胞模拟脓毒症,在体外研究了Hsp70的保护机制以及Hsp70与自噬之间的关系。

结果:

结果表明,抑制Hsp70促进脓毒症诱导的大鼠死亡,而抑制自噬则抑制脓毒症诱导的死亡。这些结果表明 Hsp70 和自噬均参与脓毒症诱发的心肌病。体外H9c2心肌细胞中Hsp70的过表达抑制了LPS诱导的细胞凋亡,而3-Ma抑制自噬也减少了LPS诱导的H9c2细胞凋亡,表明Hsp70对脓毒症诱导的心肌病的保护作用与自噬调节有关。

结论:

总体而言,这些结果表明 Hsp70 通过减弱脓毒症诱导的自噬来预防脓毒症引起的心脏损伤。

更新日期:2020-10-19
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