Naringenin Attenuates Myocardial Ischemia-Reperfusion Injury via cGMP-PKGIα Signaling and In Vivo and In Vitro Studies
Naringenin Attenuates Myocardial Ischemia-Reperfusion Injury via cGMP-PKGIα Signaling and In Vivo and In Vitro Studies
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柚皮素通过 cGMP-PKGI α 信号传导和体内外研究减轻心肌缺血再灌注损伤
DOI：
10.1155/2019/7670854
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发表时间：
2019-01-01
影响因子：
--
通讯作者：
Wang, Hui-Shan
中科院分区：
文献类型：
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作者：
Yu, Li-Ming;Dong, Xue;Wang, Hui-Shan
Endoplasmic reticulum (ER) stress and oxidative stress contribute greatly to myocardial ischemia-reperfusion (MI/R) injury. Naringenin, a flavonoid derived from the citrus genus, exerts cardioprotective effects. However, the effects of naringenin on ER stress as well as oxidative stress under MI/R condition and the detailed mechanisms remain poorly defined. This study investigated the protective effect of naringenin on MI/R-injured heart with a focus on cyclic guanosine monophosphate- (cGMP-) dependent protein kinase (PKG) signaling. Sprague-Dawley rats were treated with naringenin (50 mg/kg/d) and subjected to MI/R surgery with or without KT5823 (2 mg/kg, a selective inhibitor of PKG) cotreatment. Cellular experiment was conducted on H9c2 cardiomyoblasts subjected to simulated ischemia-reperfusion treatment. Before the treatment, the cells were incubated with naringenin (80 mu mol/L). PKGI alpha siRNA was employed to inhibit PKG signaling. Our in vivo and in vitro data showed that naringenin effectively improved heart function while it attenuated myocardial apoptosis and infarction. Furthermore, pretreatment with naringenin suppressed MI/R-induced oxidative stress as well as ER stress as evidenced by decreased superoxide generation, myocardial MDA level, gp91(phox) expression, and phosphorylation of PERK, IRE1 alpha, and EIF2 alpha as well as reduced ATF6 and CHOP. Importantly, naringenin significantly activated myocardial cGMP-PKGI alpha signaling while inhibition of PKG signaling with KT5823 (in vivo) or siRNA (in vitro) not only abolished these actions but also blunted naringenin's inhibitory effects against oxidative stress and ER stress. In summary, our study demonstrates that naringenin treatment protects against AIM injury by reducing oxidative stress and ER stress via cGMP-PKGI alpha signaling. Its cardioprotective effect deserves further clinical study.
