Protective Effects Of Exogenous ACT A On The Brain Tissue Of Neonatal Rats With Hyperbilirubinemia

Objective To explore the protective effect and possible mechanisms of exogenous activin A (ACT A) on the brain tissue of neonatal rats with hyperbilirubinemia. Methods Totally 96 seven-day-old Wistar rats were randomly divided into 4 groups:Normal control group(Co), hyperbilirubinemia control group(C1) and ACT A treatment group I and II(T1,T2). Hyperbilirubinemia control group and both ACT A treatment groups were injected bilirubin intraperitoneally (I.P.).The ACT A treatment group I and II were respectively given orally high and low dose of ACT A rightly after I.P. The specimens were collected respectively at different time points (1h, 6h,12h,24h,48h,72h). The bilirubin contents (TB) in the serum and brain tissue were measured, brain tissue ultrastructure was observed with electron microscope, brain tissue apoptosis analysis was done with flow cytometry. All data was treated by statistics. Results The neurobehavioral abnormal of C1 group was severer significantly than that of T1 and T2 groups. The TB reached a peak at 6h in serum and 12h in brain tissue after I.P. of each group. The mean TB of each time point of C1, T1, T2 groups in both serum and brain tissue were higher than those of Co group (Serum: 142.43±99.53 vs 43.43±11.75, P<0.001; 71.93±33.08 vs 43.43±11.75, P＜0.001; 105.21±63.95 vs 43.43±11.75, P＜0.001; Brain tissue:129.82±36.19 vs 73.49±31.07, P＜0.001; 90.92±27.28 vs 73.49±31.07, P<0.01; 108.56±28.65 vs 73.49±31.07, P＜0.001). The mean TB of each time point of T1, T2 in both serum and brain tissue were lower than those of C1 group (Serum:71.93±33.08 vs142.43±99.53, P＜0.001; 105.21±63.95 vs 142.43±99.53, P<0.05; Brain tissue:90.92±27.28 vs 129.82±36.19, P＜0.001; 108.56±28.65 vs 129.82±36.19, P<0.01). The mean TB of each time point of T1 group in both serum and brain tissue were lower than those of T2 group (Serum: 71.93±33.08 vs 105.21±63.95, P＜0.01; Brain tissue:90.92±27.28 vs 108.56±28.65, P<0.01). Under the electron microscope, the neuron in C1 group was damaged significantly. Plerosis of ultramicrostructurein on different degrees was found in T1 and T2 groups compared with the C1 group. The results of flow cytometry showed that the mean value of the brain cell apoptosis of each time point in C1, T1, T2 groups were higher than those of Co group (0.060±0.009 vs 0.011±0.007, P＜0.001; 0.030±0.008 vs 0.011±0.007, P＜0.001; 0.053±0.014 vs 0.011±0.007, P＜0.001). The mean value of the brain cell apoptosis of each time point in T1 and T2 groups were lower than those of C1 group (0.030±0.008 vs 0.060±0.009, P＜0.001; 0.053±0.014 vs 0.060±0.009, P＜0.05). The mean value of the brain cell apoptosis of each time point in T1 group was lower than those of T2 group (0.030±0.008 vs 0.053±0.014, P< 0.001). Conclusion The exogenous ACT A can protect the brain tissue by depressing the brain cell apoptosis of neonatal rats with hyperbilirubinemia.