褪黑素抑制氧化应激和铁死亡缓解妊娠糖尿病大鼠病理损伤

目的:探讨褪黑素对妊娠糖尿病(GDM)大鼠的治疗作用及可能作用机制.方法:将24只雌性大鼠分成4组:正常妊娠组、GDM模型组、低剂量褪黑素[5 mg/(kg·d)]治疗组及高剂量褪黑素[10mg/(kg·d)]治疗组,每组6只.不同剂量褪黑素治疗14天后,检测大鼠胰腺组织形态病理变化及细胞凋亡水平,检测血清生化指标、细...

Melatonin alleviates pathological damage in gestational diabetes mellitus rats by inhibiting oxidative stress and ferroptosis

Objective:To investigate the therapeutic effect of melatonin on gestational diabetes mellitus(GDM)rats and its possible mechanism.Methods:Twenty four female rats were divided into four groups:6 normal pregnancy rats as control group,6 rats with gestational diabetes mellitus as GDM model group,6 GDM rats treated with low dose melatonin[5mg/(kg·d)]as GDM+LM group,6 GDM rats treated with high dose melatonin[10mg/(kg·d)]as GDM+HM group.The GDM rats were treated by melatonin with different concentrations for 14 days.The morphological and pathological changes of pancreas and the level of apoptosis were detected.The serum biochemical indexes,redox status and iron content in pancreatic tissue were determined.In addition,the mRNA and protein expression of melatonin receptor gene and ferroptosis pathway related gene in pancreatic tissue were analyzed.Results:Treatment with melatonin significantly reduced the pathological damage and apoptosis level of pancreatic tissue,as well as the levels of glucose,glycosylated hemoglobin and insulin in serum.The activities of antioxidant enzymes such as CAT,GSH-Px,SOD and the levels of antioxidant GSH in pancreatic tissue were significantly increased,and the contents of H2O2,MDA and iron were obviously decreased.Melatonin significantly increased the expression of melatonin receptor gene MTNR1B in the pancreatic tissue of rats.Simultaneously,the expression of iron death pathway related genes were regulated by melatonin,the expression levels of genes GPX4 and FTH1 were significantly increased,and the expression level of gene ACSL4 was significantly decreased.Conclusions:Melatonin could inhibit the imbalance of tissue redox level,reduce apoptosis and ferroptosis which may be mediated by melatonin receptor,and then alleviate the pathological damage caused by GDM.