Effects Of Simvastatin On BDNF-TrKB Pathway And Apoptosis In Bilirubin Encephalopathy Model Rats

Objective: To investigate the effect of simvastatin on BDNF-Tr KB pathway and apoptosis in neonatal rats with bilirubin encephalopathy,and whether the neuroprotective effect is exerted through BDNF-Tr KB pathway.Methods: 7-day-old SD rats were randomly divided into NS group and T group.The T group was intraperitoneally injected with bilirubin solution at a dose of 150 mg/kg,and the NS group was intraperitoneally injected with the same amount of normal saline.After successful film-making,SD rats in T group were randomly assigned to T1 group and T2 group.The T1 group was intragastric with simvastatin at 20 mg/kg at 8 days old,and the NS group and T2 groups were intragastric with normal saline at 8 days old until 21 days old.After 12 hours of modeling and gavage of simvastatin,3 rats in each group were randomly selected for HE staining,Tunel staining,and detecting the expression levels of BDNF,Tr KB and caspase-3 in hippocampal tissues.At 7,8 and 21 days old,10 SD rats in each group were randomly selected and weighed,and behavioral tests were performed on SD rats at 21 days old.Results :(1)Body weight analysis showed that the body weight of 7-day-old T group was significantly lower than that of NS group(P< 0.01);Weight loss in 8-day-old T1 and T2 groups(P<0.05),there was no significant difference in body weight between T1 group and T2 group(P>0.05);At 21 days old,T1 and T2 groups were significantly lower than NS group(P<0.01),the body weight of T1 group was higher than that of T2 group(P<0.05).(2)Behavioral test results showed that the score of NS group was higher than that of T1 group and T2 group in the rejection response test,suspension test and neurological function test,and the score of T1 group was higher than that of T2 group,with statistical significance(P< 0.05).(3)HE staining results showed that mild vacuoles in the cytoplasm of neurons in the hippocampus and edema around neurons and blood vessels of SD rats in groups T,T1.In addition,some neurons in T group were necrotic,while nucleus pyknosis was occasionally observed in T2 group.The tissue structure of NS group hippocampus was normal.(4)Tunel staining showed that the apoptosis rate of hippocampal cells in T group was higher than that in NS group(P< 0.01),the apoptosis rate of hippocampus in NS group at 21 days old was lower than that in T1 and T2 groups(P<0.001),and T1 group was lower than T2 group(P<0.01).(5)Western Blot results showed that the expression of BDNF protein in the hippocampus of T group was higher than that of NS group at 7 days of age(P< 0.05);At 21 days old,the expression of BDNF protein in hippocampus of T1 and T2 groups was higher than that of NS group(P<0.01),and T2 group was lower than T1 group(P<0.01).At 7 days of age,the expression of Tr KB protein in T group was higher than that in NS group(P< 0.05);At 21 days old,the expression of Tr KB protein in hippocampus of T1 and T2 groups was higher than that of NS group(P<0.05),and there was no significant difference between T1 group and T2 group(P>0.05).At 7 days of age,the expression of caspase-3 protein in hippocampus of T group was higher than that of NS group(P<0.05);At 21 days old,the expression of caspase-3protein in hippocampus of T1 and T2 groups was higher than that of NS group(P< 0.01),and there was no significant difference between T1 group and T2 group(P>0.05).Conclusion: 1.Simvastatin can improve the behavior of mice with bilirubin encephalopathy;2.Simvastatin can promote the expression of BDNF and Tr KB protein and inhibit the expression of Caspase-3 protein in bilirubin encephalopathy model rats,and inhibiting apoptosis and play a neuroprotective role by activating the BDNF-Tr KB pathway in bilirubin encephalopathy model mice.