The effect of Ulinastatin on myocardial cell apoptosis and Caspase-3 channel / 中华急诊医学杂志

ABSTRACT

Objective To investigate the effect of ulinastatin on myocardial injury in rats with sepsis.Methods Thirty male SD rats were randomly (random number) divided into 3 groupssham operation group (Sham group,n=10),sepsis group (sepsis group,n=10) and ulinastatin group (UTI group,n=10).The sepsis model of the rats was subjected to cecal ligation and puncture (CLP).Rats of UTI group were given 200 000 U/kg ulinastatin at 6 hour after modeling,and dosing was repeated every 12 h.Blood samples were collected from inferior vena cava at 6,12,24,36 h after modeling for determination of cardiac troponin-Ⅰ (cTnI) and the inflammatory factor by ELISA,then the rats were sacrificed and hearts were removed for myocardial tissue stained with hematoxylin eosin (HE) staining,the expression of Bax/Bcl-2 protein level and myocardial cell apoptosis were detected by TUNEL.The level of caspase-3 protein in myocardial tissue was detected by Western-blot.Results The level of cTnI (ng/mL) in serum in UTI group at 6,12,24 and 36 h after modeling were significantly lower compared with sepsis group(P＜0.05).The protein expression levels of TNF-α and IL-6 (ng/mL) in group UTI were higher than those in Sham group,but was significantly lower than those in Sepsis group (P＜0.05).HE staining showed that inflammatory cell infiltration present in myocardial cells,edema and vacuole formation were observed in sepsis group,while those were significantly attenuated in UTI group compared with sepsis group.UTI increased the level of myocardial Bcl-2 protein in the rats (P＜0.05),and reduced the level of myocardial Bax protein (P＜0.05).TUNEL and HE staining showed apoptosis cells in UTI group was significantly reduced compared with sepsis group [(32.2±4.8)％ vs.(58.4±5.6)％,P＜0.05];Western-blot method showed the level of Caspase-3 protein in UTI group was higher than that in group sham (0.32±0.048) vs.(0.12±0.03),P＜0.05],but significantly lower than that of Sepsis group [(0.32±0.048) vs.(0.55±0.052),P＜0.05].Conclusions Ulinastatin can reduce proinflammatory mediators release in the blood of sepsis rats,and inhibit the apoptosis of myocardial cells protecting myocardial cells through the regulation of the Caspase-3 pathway during sepsis.