中国临床药理学杂志2024，Vol.40Issue(10)：1468-1472,5.DOI:10.13699/j.cnki.1001-6821.2024.10.016
齐墩果酸激活GPR39对发育期惊厥性脑损伤大鼠神经发育的影响
Effects of oleanolic acid activation of GPR39 on neural development in developmental convulsive brain injury rats
摘要
Abstract
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.关键词
齐墩果酸/发育期惊厥性脑损伤/神经发育/学习记忆能力/G蛋白偶联受体39/沉默信息调节因子1/受体γ辅激活因子1α/核因子E2相关因子2信号Key words
oleanolic acid/developmental convulsive brain injury/neurodevelopment/learning and memory ability/G protein-coupled receptor 39/silence information regulatory factor 1/receptor-γ coactivator 1α/nuclear factor E2 associated factor 2 signaling分类
医药卫生引用本文复制引用
李振宏,纪剑清,许运琳..齐墩果酸激活GPR39对发育期惊厥性脑损伤大鼠神经发育的影响[J].中国临床药理学杂志,2024,40(10):1468-1472,5.基金项目
博士科研启动基金资助项目(Bsqd2018004) （Bsqd2018004）
