AIM To investigate possible mechanisms of Kawasaki disease-related myocardial injury in a rat model of Kawasaki disease established utilizing Lactobacillus casei cell wall extract (LCWE).
METHODS Forty-five one-month old SD rats were randomly divided into control group, LCWE model group and 4-phenylbutyrate (4-PBA) treatment group. After 4 weeks of modeling, the content of Lcn 2 in the plasma and myocardial tissue homogenates of Kawasaki disease rats was detected by ELISA. The heart function of rats was detected by echocardiography. Paraffin sections were made from rat myocardial tissue and TUNEL staining was performed. Marker changes in expression of rat endoplasmic reticulum stress were detected by Western blotting. The primary culture of neonatal rat cardiomyocytes was performed in vitro. Cell viability, Caspase 3 activity, and endoplasmic reticulum stress were measured 48h after Lcn 2 treatment.
RESULTS The levels of Lcn 2 in Kawasaki disease rats were significantly higher than those in the control group (P<0.05). Lcn 2 induced apoptosis in cardiomyocytes. ER stress markers, ATF6, CHOP, p-PERK and p-elF2α in cardiomyocytes all increased, resulting in a significant increase in apoptotic signals Caspase 12 and cleave-Caspase 3 levels. Quantitative detection of Caspase 3 activity in cardiomyocytes demonstrated significant increases (P<0.05). Inhibition of endoplasmic reticulum stress by 4-PBA reduced the levels of ATF6, CHOP, p-PERK and p-elF2α and decreased the levels of Caspase 12 and cleave-Caspase 3 (P<0.05), which in turn relieved cardiomyocyte apoptosis and improved cardiac function in Kawasaki disease rats.
CONCLUSION Kawasaki disease induces systolic diastolic dysfunction and is accompanied by a significant increase in Lcn2. The direct effect of Lcn2 on cardiomyocytes is pro-apoptotic endoplasmic reticulum stress. Inhibition of endoplasmic reticulum stress in Kawasaki disease can inhibit myocardial apoptosis and improve cardiac function.
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