Melatonin attenuates aortic oxidative stress injury and apoptosis in STZ-diabetes rats by Notch1/Hes1 pathway.

Oxidative stress injury is an important link in the pathogenesis of diabetes, and reducing oxidative stress damage caused by long-term hyperglycemia is an important diabetic treatment strategy. Melatonin has been proved to be a free radical scavenger with strong antioxidant activity, and its protective effect on diabetes and the complications has been confirmed. However, the role and potential mechanism of melatonin in oxidative stress injury of diabetic aorta have not been reported. Besides, Notch signaling pathway plays an important role in vascular growth, differentiation, and apoptosis. We speculated that melatonin could improve oxidative stress injury of diabetic aorta through Notch1/Hes1 signaling pathway. STZ-induced diabetic rats and vascular smooth muscle cells (VSMCs) cultured with high glucose were treated with or without melatonin, melatonin receptor antagonist Luzindole, γ-secretase inhibitor DAPT respectively. We found that melatonin could improve the oxidative stress injury of diabetic aorta and reduce the apoptosis of VSMCs. Interestingly, melatonin could activate Notch1 signaling pathway, play an antioxidant role, and reduce the expression of apoptosis-related proteins. However, these protective effects could be largely eliminated by Luzindole or DAPT. We concluded that the repression of Notch1 signaling pathway would inhibit the repair of oxidative stress injury in diabetes. Melatonin could ameliorate oxidative stress injury and apoptosis of diabetic aorta by activating Notch1/Hes1 signaling pathway.