Department of Emergency Intensive Care Unit, Beijing LuHe Hospital, Capital Medical University, Beijing, China
Department of Emergency Intensive Care Unit, Beijing LuHe Hospital, Capital Medical University, Beijing, China.
Ann Clin Lab Sci. 2020 Nov;50(6):769-774.
To investigate the possible role of Naringenin in AMPK signaling pathway in LPS-induced septic cardiac dysfunction in mice and to elucidate the inherent mechanism.
Male C57 mice were used in the establishment of mouse sepsis model. The effect of Naringenin on septic cardiac dysfunction was observed. Echocardiographic parameters were recorded. Western blot was employed to detect the expressions of BCL-2, BAX, cleaved caspase-3, pNF-kB and IkB-α. Myocardial mitochondria were isolated and extracted. Real-time PCR was applied to detect the expressions of Cox4i, Cox5a mRNA, mt-Nd1, mt-Nd2, mt-Co1 and mt-Co2 mRNA. Western blot was employed to detect the expressions of Complex I, Complex II, and OPA1 to evaluate the effects of Naringenin on myocardial mitochondrial biology and function in septic cardiac dysfunction.
The expressions of TNF-α, IL-6, pNF-κB and IκB-α have changed after Naringenin treatment. IκB-α expression was decreased, expressions of TNF-α, IL-6 and pNF-κB were increased. Naringenin has significantly inhibited AMPK and ACC phosphorylation, and decreased PGC1α expression. Moreover, Naringenin reversed the increased expressions of PGC1α and phosphorylation of AMPK and ACC by U75302 treatment, and decreased the expressions of complex I, complex II and OPA1.
Naringenin inhibits LTB4/BLT1 receptors to attenuate cardiomyocyte inflammation and apoptosis, which may mediate the protective effect of anti-septic cardiac dysfunction by activating AMPK signaling pathway and inhibiting NF-κB signaling and mitochondrial damage.
探讨柚皮素在 LPS 诱导的脓毒症性心功能障碍小鼠 AMPK 信号通路中的可能作用，并阐明其内在机制。
采用雄性 C57 小鼠建立脓毒症模型，观察柚皮素对脓毒症性心功能障碍的影响，记录超声心动图参数。采用 Western blot 检测 BCL-2、BAX、cleaved caspase-3、pNF-κB 和 IkB-α的表达。分离提取心肌线粒体，实时 PCR 检测 Cox4i、Cox5a mRNA、mt-Nd1、mt-Nd2、mt-Co1 和 mt-Co2 mRNA 的表达，Western blot 检测 Complex I、Complex II 和 OPA1 的表达，评估柚皮素对脓毒症性心功能障碍心肌线粒体生物学和功能的影响。
柚皮素处理后 TNF-α、IL-6、pNF-κB 和 IκB-α的表达发生变化。IκB-α表达减少，TNF-α、IL-6 和 pNF-κB 的表达增加。柚皮素明显抑制了 AMPK 和 ACC 的磷酸化，降低了 PGC1α的表达。此外，柚皮素逆转了 U75302 处理引起的 PGC1α和 AMPK、ACC 磷酸化的增加，并降低了复合物 I、复合物 II 和 OPA1 的表达。
柚皮素抑制 LTB4/BLT1 受体，减轻心肌细胞炎症和凋亡，可能通过激活 AMPK 信号通路、抑制 NF-κB 信号通路和线粒体损伤来介导其抗脓毒症性心功能障碍的保护作用。
