Resveratrol alleviates Kawasaki disease-induced myocardial injury by activating Notch1/Hes1 signaling
XIONG Fengmei1, KONG Lingheng2, SUN Na2, DING Hui3, SHI Zhaoling4
1. Department of Pharmacy,Xi'an Children's Hospital,Xi'an 710003,China; 2. Institute of Basic Medical Science,Xi'an Medical University,Xi'an 710021,China; 3. Department of Intensive Care,4. Department of Respiratory Asthma,Children's Hospital,the Second Affiliated Hospital of Shaanxi University of Chinese Medicine,Xianyang 712000,China
Abstract:Objective To investigate the role of resveratrol (Res) in Kawasaki disease-induced myocardial injury and the effect of Notch1/Hes1 signaling pathway.Methods Forty-eight young male SD rats were randomly divided into the control group,Res group,LCWE-induced Kawasaki disease group (KD),and Res treatment group (Res+KD).The control group was intraperitoneally injected with 0.5 ml saline,Res group with resveratrol (100 mg/kg),KD group with 0.5 ml LCWE (1 mg/ml),and Res+KD group with 0.5 ml LCWE (1 mg/ml) and resveratrol (100 mg/kg).After four weeks,the rat cardiac function was tested by ultrasonic testing,and myocardial TNF-α and IL-1β contents were detected by ELISA.The apoptotic index was detected by TUNEL staining.The morphological changes in myocardial fibers were analyzed via HE staining.Western blot was used to detect the protein levels of Bcl2,Bax,Notch1,and Hes1.Results There was no significant difference between the Res group and the control group (P>0.05).Compared with the control group,the left ventricular ejection fraction (LVEF),fractional shortening (LVFS) and expression of Bcl2 were significantly decreased in the KD group (P<0.05),but the expression of Bax was increased (P<0.05).The myocardial TNF-α and IL-1β contents and apoptotic index were increased (P<0.05),while the levels of Notch1 and Hes-1 were reduced (P<0.05).Res could alleviate myocardial injury induced by KD and reduce the inflammation in the myocardium (P<0.05).Conclusions KD can induce myocardial injury by increasing apoptosis and inflammation via inhibition of Notch1/Hes1 signaling.Res can activate Notch1/Hes1 signaling to inhibit myocardial apoptosis and inflammation and improve cardiac function in case of KD-induced myocardial injury.
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