Abstract: Abstract: Objective To explore the protective effect and molecular mechanism of silibinin (SIL) on myocardial injuryin endotoxemic mice. Methods Twenty-four C57BL/6 mice were grouped as follows: Control group, SIL group, LPS group and LPS + SIL group (n=6 in each group). The mouse model of endotoxemic cardiomyopathy was established by intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg). Three days before LPS injection, SIL was administered daily by gavage at a dose of 100 mg/kg for 3 times in the SIL group and the LPS+SIL group. The mice in the Control group and the SIL group were treated with normal saline (0.2 mL, by gavage) for 3 times. Six hours after LPS injection, the cardiac contractile function was detected by ultrasound in mice, the expression levels of serum IL-1β and TNF-α were detected by ELISA, the production of reactive oxygen species (ROS) in heart tissue was observed by DHE staining, the apoptotic ratio was detected by TUNEL staining and the expression of apoptosis-related proteins (Bax, Bcl-2, Caspase 3) and NOX2 were detected by Western blot assay. Results Compared with the Control group, the left ventricular ejection fraction, left ventricular fractional shortening and Bcl-2 expression were significantly decreased, while ROS production, the expressions of NOX2, Bax, Caspase 3, IL-1β, TNF-α and the apoptotic ratio were significantly increased in the LPS group (P＜0.05).Compared with the LPS group, silibinin pretreatment significantly improved the above changes caused by LPS (P＜0.05).Compared with the Control group, SIL alone showed little influence on the parameters metioned above (P＞0.05).Conclusion Silibinin can effectively alleviate myocardial injury in endotoxemic mice, and its cardioprotective role is possibly mediated by inhibiting oxidative stress, inflammatory response and apoptosis.

Key words: endotoxemia, lipopolysaccharides, myocardial contraction, apoptosis, reactive oxygen species, inflammation, silibinin