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

作　　者：李振宏 纪剑清 许运琳 LI Zhen-hong;JI Jian-qing;XU Yun-lin(Department of Pediatrics,The Affiliated Ganzhou Hospital of Nanchang University,Ganzhou 341000,Jiangxi Province,China)

机构地区：[1]南昌大学附属赣州医院儿科,江西赣州341000

出　　处：《中国临床药理学杂志》2024年第10期1468-1472,共5页The Chinese Journal of Clinical Pharmacology

基　　金：博士科研启动基金资助项目(Bsqd2018004)。

摘　　要：目的研究齐墩果酸(OA)对发育期惊厥性脑损伤大鼠神经发育的改善作用及其作用机制。方法将SD大鼠随机分为RS组(青霉素诱导大鼠模型)、RS+OA组(青霉素+20 mg·kg^(-1)OA)、RS+OA+GPR39 CRISPR组[青霉素+20 mg·kg^(-1)OA+5×10^(8)PFU的G蛋白偶联受体39(GPR39)CRISPR质粒]、RS+OA+EX527组[青霉素+20 mg·kg^(-1)OA+10 mg·kg^(-1)的沉默信息调节因子1(SIRT1)抑制剂EX527],每组均为10只大鼠。通过神经发育实验、旷场实验及新异物实验检测大鼠神经发育、学习记忆能力;用免疫荧光染色检测小胶质细胞GPR39表达水平;用试剂盒检测氧化应激相关表达;用实时荧光定量聚合酶链反应(RT-qPCR)实验检测相关基因mRNA表达水平。结果RS组、RS+OA组、RS+OA+GPR39 CRISPR组和RS+OA+EX527组的GPR39 mRNA相对表达水平分别为1.00±0.05、1.29±0.14、0.97±0.11和1.05±0.09,SIRT1 mRNA相对表达水平分别为1.00±0.10、1.33±0.20、1.05±0.09和1.01±0.06,受体γ辅激活因子1α(PGC-1α)mRNA相对表达水平分别为1.00±0.16、1.34±0.15、1.03±0.07和0.93±0.11,核因子E2相关因子2(Nrf2)mRNA相对表达水平分别为1.00±0.08、1.45±0.21、0.89±0.10和0.96±0.08。RS组的上述指标与RS+OA组比较,RS+OA+GPR39 CRISPR组、RS+OA+EX527组的上述指标分别与RS+OA组比较,在统计学上差异均有统计学意义(均P<0.05)。结论OA可能通过GPR39激活SIRT1/PGC-1α/Nrf2通路抑制氧化应激途径,改善青霉素诱导的发育期惊厥性脑损伤大鼠神经发育及学习记忆能力的影响。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+CPR39 CRISPR group[penicillin+20 mg·kg OA+5×10^(8)PFU G-protein-coupled receptor 39(CPR39)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).ResulstsThe expression levels of GPR39 mRNA in RS group,RS+OA group,RS+0A+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-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/PCC-lα/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 

分 类 号：R28[医药卫生—中药学]