蛋白激酶B
PI3K/AKT/mTOR通路
细胞凋亡
LY294002型
败血症
下调和上调
内生
内分泌学
伊诺斯
脂多糖
内科学
化学
心肌细胞
药理学
医学
一氧化氮
一氧化氮合酶
生物化学
基因
作者
Yun Xing,Tian Tian,Xue Zhang,Duomeng Yang,Chanjuan Zhang,Miao Wang,Yiyang Wang,Tao Luo,Zhi Wang,Huadong Wang,Hongmei Li
出处
期刊:Shock
[Ovid Technologies (Wolters Kluwer)]
日期:2024-03-25
标识
DOI:10.1097/shk.0000000000002354
摘要
ABSTRACT β 3 -adrenergic receptor (β 3 -AR) has been proposed as a new therapy for several myocardial diseases. However, the effect of β 3 -AR activation on sepsis-induced myocardial apoptosis is unclear. Here, we investigated the effect of β 3 -AR activation on the cardiomyocyte apoptosis and cardiac dysfunction in cecal ligation and puncture (CLP)-operated rats and lipopolysaccharide (LPS)-treated cardiomyocytes. We found that β 3 -AR existed both in adult rat ventricular myocytes (ARVMs) and H9c2 cells. The expression of β 3 -AR was upregulated in LPS-treated ARVMs and the heart of CLP rats. Pretreatment with β 3 -AR agonist, BRL37344, inhibited LPS-induced cardiomyocyte apoptosis and caspase-3, -8 and -9 activation in ARVMs. BRL37344 also reduced apoptosis and increased the protein levels of PI3K, p-Akt Ser473 and p-eNOS Ser1177 in LPS-treated H9c2 cells. Inhibition of PI3K using LY294002 abolished the inhibitory effect of BRL37344 on LPS-induced caspase-3, -8, and -9 activation in H9c2 cells. Furthermore, administration of β 3 -AR antagonist, SR59230A (5 mg/kg), significantly decreased the maximum rate of left ventricular pressure rise (+dP/dt) in CLP-induced septic rats. SR59230A not only increased myocardial apoptosis, reduced p-Akt Ser473 and Bcl-2 contents, but also increased mitochondrial Bax, cytoplasm cytochrome c, cleaved caspase-9 and cleaved caspase-3 levels of the myocardium in septic rats. These results suggest that endogenous β 3 -AR activation alleviates sepsis-induced cardiomyocyte apoptosis via PI3K/Akt signaling pathway and maintains intrinsic myocardial systolic function in sepsis.
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