Regulation of LKB1/AMPK/Nrf2 signaling pathway by theaflavins on cardiac protection in mice with diabetic cardiomyopathy

Objective To investigate the protective effect of Theaflavine (TF) on the heart of diabetic cardiomyopathy (DCM) mice and its mechanism.Methods Sixty male wild type (WT) C57BL/6J mice aged 6-8 weeks were randomly divided into 5 groups. The normal control (WT) group, DCM model (DCM) group, low dose of theaflavine 5mg/kg (DCM+TF5) group, high dose of theaflavine 50mg/kg (DCM+TF50) group, high dose of theaflavine 50mg/kg (DCM+TF50) group and high dose of theaflavine 50mg/kg (DCM+TF50) group +Dorsomorphin (AMPK inhibitor, 0.2mg/kg) (DCM+TF50+Dorsomorphin) group. There were 12 mice in each group. DCM model was induced by intraperitoneal injection of 50 mg/kg streptozotocin and 45% high-fat diet for 20 weeks. The mice in the control group were intraperitoneally injected with the same volume of citrate buffer and fed with ordinary diet. Blood glucose and body weight were measured every two weeks during the experiment and cardiac function were measured by small animal ultrasound. Intraperitoneal glucose tolerance test (IPGTT) was performed after the intervention, and HE staining and Masson staining were used to detect the pathological changes of myocardial tissue in each group. Elisa and Westernblot were used to detect oxidative stress, inflammatory markers and protein expression of LKB1/AMPK/Nrf2 pathway in myocardial tissue of mice in each group.Results Compared with the DCM model group, the mice in the low - and high-dose theaflavin groups had alleviated myocardial tissue damage, reduced oxidative stress, reduced release of inflammatory factors, and increased protein expression of LKB1/AMPK/Nrf2 signaling pathway（P＜0.05）. Compared with the theaflavin-low dose group, the myocardial tissue injury of the mice in the theaflavin-high dose group was further alleviated.Conclusion Theaflavine can alleviate myocardial injury and fibrosis in diabetic mice by activating LKB1/AMPK/Nrf2 signaling pathway.