Luteolin attenuates sepsis‑induced myocardial injury by enhancing autophagy in mice

Wu,Bin; Song,Haixu; Fan,Miaomiao; You,Fei; Zhang,Liang; Luo,Jian; Li,Junzhi; Wang,Lingpeng; Li,Congye; Yuan,Ming

doi:10.3892/ijmm.2020.4536

Luteolin attenuates sepsis‑induced myocardial injury by enhancing autophagy in mice

Authors:
- Bin Wu
- Haixu Song
- Miaomiao Fan
- Fei You
- Liang Zhang
- Jian Luo
- Junzhi Li
- Lingpeng Wang
- Congye Li
- Ming Yuan
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Affiliations: Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China, Department of Cardiology, Xi'an Central Hospital, Xi'an, Shaanxi 710004, P.R. China, Department of Internal Medicine (VIP), First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China, Department of Pathology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China, Department of Cardiology, First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China
Published online on: March 11, 2020 https://doi.org/10.3892/ijmm.2020.4536
Pages: 1477-1487
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sepsis‑induced cardiomyopathy (SIC) is a complication of severe sepsis and septic shock characterized by an invertible myocardial depression. This study sought to explore the potential effects and mechanism of luteolin, a flavonoid polyphenolic compound, in lipopolysaccharide (LPS)‑induced myocardial injury. Experimental mice were randomly allocated into 3 groups (25 mice in each group): The control group (NC), the LPS group (LPS) and the LPS + luteolin group (LPS + Lut). Before the SIC model was induced, luteolin was dissolved in DMSO and injected intraperitoneally for 10 days into LPS + Lut group mice. NC group and LPS group mice received an equal volume of DMSO for 10 days. On day 11, the animal model of sepsis‑induced cardiac dysfunction was induced by intraperitoneal injection of LPS. A total of 12 h after LPS injection, measurements and comparisons were made among the groups. Luteolin administration improved cardiac function, attenuated the inflammatory response, alleviated mitochondrial injury, decreased oxidative stress, inhibited cardiac apoptosis and enhanced autophagy. In addition, luteolin significantly decreased the phosphorylation of AMP‑activated protein kinase (AMPK) in septic heart tissue. The protective effect of luteolin was abolished by 3‑methyladenine (an autophagy inhibitor) and dorsomorphin (compound C, an AMPK inhibitor), as evidenced by decreased autophagic activity, destabilized mitochondrial membrane potential and increased apoptosis in LPS‑treated cardiomyocytes, but was mimicked by 5‑aminoimidazole‑4‑carboxamide ribonucleotide (an AMPK activator), suggesting that luteolin attenuates LPS‑induced myocardial injury by increasing autophagy through AMPK activation. Luteolin may be a promising therapeutic agent for treating SIC.

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