Geniposide protects against sepsis -induced myocardial dysfunction through AMPK α-dependent pathway
Geniposide protects against sepsis -induced myocardial dysfunction through AMPK α-dependent pathway
复制标题
京尼平苷通过 AMPKα 依赖性途径预防脓毒症引起的心肌功能障碍
DOI：
10.1016/j.freeradbiomed.2020.02.011
复制
发表时间：
2020-05-20
影响因子：
7.4
通讯作者：
Ma, Zhen-Guo
中科院分区：
文献类型：
--
作者：
Song, Peng;Shen, Di-Fei;Ma, Zhen-Guo
Uncontrolled inflammatory response and subsequent cardiomyocytes loss (apoptosis and pyroptosis) are closely involved in sepsis -induced myocardial dysfunction. Our previous study has found that geniposide (GE) can protect the murine hearts against obesity -induced inflammation. However, the effect of GE on sepsis -related cardiac dysfunction is still unknown. Mice were exposed to lipopolysaccharide (LPS) to generate sepsis -induced myocardial dysfunction. And 50 mg/kg GE was used to treat mice for consecutive 7 days. Our results showed that GE treatment significantly improved survival rate and cardiac function, and suppressed myocardial in- flammatory response, as well as myocardial loss in LPS-treated mice. Those effects of GE were largely abolished in NOD -like receptor protein 3 (NLRP3)-deficient mice. Further detection revealed that the inhibition of NLRP3 inflammasome activation depended on the reduction of p47phox by GE. GE treatment restored the phosphor- ylation and activity of AMP -activated protein kinase ? (AMPK ?) in the hearts of sepsis mice, and knockout of AMPK ? abolished the protection of GE against reactive oxygen species (ROS) accumulation, NLRP3 in- flammasome activation and cardiomyocytes loss in sepsis mice. In conclusion, our findings revealed that GE activated AMPK ? to suppress myocardial ROS accumulation, thus blocking NLRP3 inflammasome-mediated cardiomyocyte apoptosis and pyroptosis and improving cardiac function in mice with sepsis.
