The Effect And Mechanism Of Melatonin In Coronary Artery Lesions Of Kawasaki Disease

Objective: Kawasaki disease(KD)is an acute,systemic vascular inflammatory disease.Coronary artery lesion is the most serious complication.Endothelial dysfunction caused by inflammatory cascade and oxidative stress injury is of great importance during the process.Melatonin has anti-inflammatory and anti-oxidative effects and plays a protective role in various cardiovascular diseases.This study investigated whether melatonin could protect coronary artery lesions by improving endothelial function in the acute phase of KD.Methods:(1)Serum samples from children with KD of acute phase,normal control group(NC),and febrile control(FC)were obtained.Serum levels of SDC-1,IL-6,sICAM-1 were detected by ELISA.(2)The animal model of coronary arteritis was constracted by Lactobacillus casei cell wall extract(LCWE)injection and treated with melatonin.Cardiological pathologic examinations were performed,the serum SDC-1 was detected by ELISA,the expression levels of IL-1?,TNF-?,ICAM-1,SOD-1,GPx and SOD-2 were detected by RT-qPCR or WB.(3)After pretreatment with melatonin,human coronary artery endothelial cells(HCAECs)were stimulated with TNF-?.The total SOD activities were detected,and the expression levels of ET-1,IL-6,MMP-9,sICAM-1 were detected by RT-qPCR.SDC-1 levels in cell supernatant were detected by ELISA.Results:(1)Compared with the healthy control group and the fever control group,serum SDC-1 levels were significantly increased,albumin and hemoglobin were significantly decreased in KD patients(p<0.05).In KD patients with coronary artery lesions SDC-1 was significantly increased while albumin and hemoglobin were significantly decreased(p<0.05).After IVIG treatment,the levels of IL-6,sICAM-1 and resistin were decreased while the level of SDC-1 was significantly increased(p<0.05).(2)The inflammatory cells infiltration was alleviated in coronary arteritis mice after melatonin treatment.The mRNA expression levels of IL-1?,TNF-?,sICAM-1 were decreased,and SOD-1,SOD-2,GPx,catalase were increased.The vascular endothelial damage was recovered under the electron microscopy.The serum SDC-1 levels were significantly decreased.(3)After pretreatment with different concentrations of melatonin,10 ng/ml TNF-? was added to HCAECs for 12 hours,and then mRNA expression levels of IL-6,MMP-9,ICAM-1,ET-1 decreased and SDC-1 levels in the supernatant decreased,the total SOD activity restored.Conclusion:(1)Serum levels of SDC-1 which associated with coronary artery lesions may reflect the state of vascular endothelial damage and the inflammation of vascular in the acute phase of Kawasaki disease.(2)Melatonin could inhibit the degradation of SDC-1 in coronary arteritis.(3)Melatonin could protect the endothelium by inhibiting the degradation of SDC-1 induced by TNF-?.