Effects of oleanolic acid activation of GPR39 on neural development in developmental convulsive brain injury rats
Objective To investigate the effect of oleanolic acid(OA)on neurodevelopment and its mechanism in rats with developmental convulsive brain injury.Methods SD rats were randomly divided into RS group(penicillin induced rat model),RS+OA group(penicillin+20 mg·kg-1 OA),RS+OA+GPR39 CRISPR group[penicillin+20 mg·kg-1 OA+5 × 108 PFU G-protein-coupled receptor 39(GPR39)CRISPR plasmid],RS+OA+EX527[Penicillin+20 mg·kg-1 OA+10 mg·kg-1 silenced information regulatory factor 1(SIRT1)inhibitor EX527],and each group consisted of 10 rats.Neural development,learning and memory ability of rats were measured by neural development experiment,open field experiment and new foreign body experiment.The expression level of GPR39 in microglia was detected by immunofluorescence staining.The expression of oxidative stress was detected by the kit.mRNA expression levels of related genes were detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).Results The expression levels of GPR39 mRNA in RS group,RS+OA group,RS+OA+GPR39 CRISPR group and RS+OA+EX527 group were 1.00±0.05,1.29±0.14,0.97±0.11 and 1.05±0.09;SIRT1 mRNA expression levels were 1.00±0.10,1.33±0.20,1.05±0.09 and 1.01±0.06;receptor-γ coactivator 1α(PGC-1α)mRNA were 1.00±0.16,1.34±0.15,1.03±0.07 and 0.93±0.11;nuclear factor E2 associated factor 2(Nrf2)mRNA were 1.00±0.08,1.45±0.21,0.89±0.10 and 0.96±0.08.Compared between RS+OA group and RS group,RS+OA+GPR39 CRISPR group or RS+OA+EX527 group were compared with RS+OA group,the differences of the above indicators were statistically significant(all P＜0.05).Conclusion OA may inhibit the oxidative stress pathway by activating SIRT1/PGC-1α/Nrf2 pathway through GPR39,and improve the neurodevelopment and learning and memory ability of rats with developmental convulsive brain injury induced by penicillin.
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