Ginsenoside Rb1 activates janus kinase 2/signal transducer and activator of transcription 3 pathway to reduce myocardial injury in mice with Kawasaki disease / 中国小儿急救医学

ABSTRACT

Objective:To investigate the therapeutic effect and signaling pathway of ginsenoside Rb1 on myocardial injury in mice with Kawasaki disease.Methods:BALB/C mice aged 5-6 weeks were randomly divided into control group, model group, aspirin group, ginsenoside Rb1 low dose group(50 mg/kg) and high dose group(100 mg/kg), with 12 mice in each group.Except the control group, other groups were treated with intermittent intraperitoneal injection of 10% bovine serum albumin saline solution to induce Kawasaki disease myocardial injury pathological model with a total of 6 days(twice a day); aspirin group, Rb1 low and high-dose group were given corresponding drugs by gavage for 20 days after modeling.The pathological changes of myocardial tissue were observed by hematoxylin eosin staining.The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) and cardiac troponin I(cTnI) in serum and myocardial tissue were detected by ELISA.The activities of creatine kinase(CK), creatine kinase isoenzyme(CK-MB), lactate dehydrogenase(LDH), α-hydroxybutyrate dehydrogenase(α-HBDH) and aspartate aminotransferase(AST) in serum were detected by enzyme coupling method.The expression levels of janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signaling pathway related proteins in myocardial tissue were detected by Western blot.Results:High dose of Rb1 significantly improved myocardial fiber rupture and tear, inflammatory infiltration and necrosis induced by myocardial injury in model group.ELISA results showed that, compared with the model group, high-dose Rb1 could significantly inhibit the high expression of tumor necrosis factor-α, interleukin-1β, interleukin-6, which were restored to the level of the control group, and there was a dose-dependent relationship between the low and high-dose groups( P<0.05). The results of enzyme coupling method showed that creatine kinase, creatine kinase isoenzyme-MB, lactate dehydrogenase, α-hydroxybutyrate dehydrogenase, and aspartate aminotrasferase in Rb1 high-dose group were restored to the level in control group, and there was a dose-dependent relationship between low and high-dose group( P<0.05). At the same time, compared with model group, Rb1 high-dose group significantly down regulated the expression level of cardiac troponin I( P<0.05). Western blot results showed that, compared with the model group, Rb1 significantly increased the relative expression levels of p-JAK2/JAK2, p-STAT3/STAT3 and B-cell lymphoma-2(Bcl-2)/β-actin, and significantly decreased the expression levels of Cleaved caspase-3/β-actin in a dose-dependent manner( P<0.05). Conclusion:Ginsenoside Rb1 can effectively reduce the myocardial injury induced by Kawasaki disease mice.The high-dose group of Rb1 can recover to the level of the control group, and the curative effect is related to the dosage of Rb1.Ginsenoside Rb1 may activate JAK2/STAT3/Bcl-2 signaling pathway, thus down regulate the expression of Cleaved caspase-3, and inhibit cardiomyocyte apoptosis and inflammation.