The effects of hyperbilirubinemia on the myocardium of newborn rats / 中国新生儿科杂志

ABSTRACT

Objective:To study the influences of different levels of hyperbilirubinemia on the myocardium of newborn rats.Methods:Ninety-six 7-day-old newborn SD rats were selected and randomly assigned into control group (n=32, intraperitoneal injection of normal saline 0.5 ml), test group 1 (n=32, intraperitoneal injection of bilirubin solution 100 mg/kg) and test group 2 (n=32, intraperitoneal injection of bilirubin solution 200 mg/kg). Four time points were set at 0 h, 8 h, 24 h and 48 h. The general conditions of 8 rats from every group at each time point were recorded. The total serum bilirubin (TSB), cardiac troponin I (cTnI),heart fatty acid-binding protein (H-FABP) and B-type natriuretic peptide (BNP) were examined. The heart was removed and the pathological changes of the myocardium were observed under microscope. The caspase-3, B-cell lymphoma-2 protein (bcl-2) and bcl-2-associated X protein (bax) were tested. Using SPSS 20.0 statistical software, two-way ANOVA analysis of variance was conducted.Results:The TSB in test group 1 and 2 at 8~48 h were 2.5~4.4 times and 3.5~7.4 times higher than at 0 h [(20.8±3.0~36.5±10.4) μmol/L and (31.9±12.3~67.4±19.0) μmol/L vs. (8.4±2.1) μmol/L and (9.1±2.9) μmol/L]. No significant changes existed in cardiac histopathology at each time point among the three groups. At 48 h, as TSB level increased, the expression of apoptosis-related proteins caspase-3 and bax increased and the expression of bcl-2 decreased. Significant differences existed in the protein levels between any two groups (all P<0.05), except that bcl-2 in test group 1 was similar to control group ( P=0.255). With the prolonged duration of hyperbilirubinemia in test group 2, the expression of caspase-3 and bax increased, while the expression of bcl-2 decreased. Statistically significant differences existed in the protein levels between any two time points (all P<0.05), except that bax in 8 h subgroup was similar to 12 h subgroup ( P=0.820), and bcl-2 in 8 h subgroup was similar to 0 h subgroup ( P=0.064). The cTnI at 8 h, 24 h and 48 h in test group 1 and 2 were all significantly higher than the control group (all P<0.05),however, no significant differences existed between test group 1 and 2 (all P>0.05). H-FABP and BNP showed no significant differences among the three groups at any time point (all P>0.05). Conclusions:Hyperbilirubinemia can induce apoptosis of myocardial cells in newborn rats in a concentration- and time-dependent manner. Hyperbilirubinemia shows no significant effects on cardiac tissue pathology. Hyperbilirubinemia may cause mild injury to myocardium of newborn rats. The injury shows no correlation with TSB level and BNP level was not influenced.