Effect of ulinastatin on cell apoptosis mediated by mitochondrial pathways in endotoxic myocardial injury rats

Abstract

Objective To discuss the influence of ulinastatin on cell apoptosis mediated by mitochondrial pathways in endotoxic myocardial injury rats. Methods A total of 24 male Wistar rats were randomly divided into three groups: the control group, the endotoxin group and the ulinastatin group, 8 rats in each group. Rats in the endotoxin group and ulinastatin group both received 10 mg/kg lipopolysaccharide by intraperitoneal injection, and rats in the ulinastatin group were given 20 000 U/kg ulinastatin 1 h after injection. Rats in the control group only injected equal dose saline at the same time. The pathological changes of myocardial tissues were observed. The serum troponin T (cTnT), and brain natriuretic peptide (BNP) levels were detected by enzyme-linked immunosorbent assay, and the myocardial cell apoptosis index was calculated. The expressions of Bcl-2, Bax, CytC, Caspases-3 proteins in myocardial cell were also determined by immunohistochemistry. Results Rats in the endotoxin group had severe myocardial tissue damage, while rats in the ulinastatin group had a slightly myocardial tissue damage. The levels of cTnT, BNP all showed significantly differences among these three groups (F = 69.217, 18.250; all P < 0.05); the cTnT expressions [(20.3 ± 1.0), (18.7 ± 1.3), (12.2 ± 1.0) μg/L] and BNP expressions [(26.6 ± 1.4), (23.0 ± 2.4), (17.0 ± 1.6) μg/L] in the endotoxin and ulinastatin groups were much higher than those in the control group, and were highest in the endotoxin group (all P < 0.05). The myocardial cell apoptosis index in the ulinastatin group was much lower than that in the endotoxin group [(19.8 ± 1.7)% vs. (22.6 ± 1.2)%, t = 3.675, P = 0.020]. Meanwhile, the expression of Bcl-2 in the endotoxin and ulinastatin groups was much higher than that in the control group [(80.3 ± 3.8), (76.6 ± 2.90), (49.6 ± 3.9)], and was highest in the endotoxin group (all P < 0.05); the expressions of Bax [(70.8 ± 1.7), (80.0 ± 4.8), (99.7 ± 5.6)], CytC [(120 ± 5), (132 ± 3), (151 ± 7)] and Caspases-3 [(108.8 ± 4.0), (113.9 ± 5.2), (157.2 ± 2.5)] in the endotoxin and ulinastatin groups were lower than those in the control group, and were lowest in the endotoxin group (all P < 0.05). Conclusion Ulinastatin may reduce the occurrence of myocardial cell apoptosis by inhibiting the activation of mitochondrial pathways, and plays a certain protective role on endotoxic myocardial injury. Key words: Endotoxemia; Apoptosis; Myocardium; Mitochondria; Rats; Ulinastatin