激活LXR对海马神经元神经甾体合成的促进作用

Promoting role of liver X receptor activation in synthesis of neurosteriod in primary hippocampal neurons

目的:研究肝X受体(LXR)激活对海马神经元神经甾体合成的影响.方法:将大鼠海马神经元体外培养至第7日,在培养液中加入2.0μmol/L TO901317,继续培养48 h.应用高效液相-质谱联用(HPLC-MS)分离测定培养液中游离型神经甾体孕烯醇酮(PREG)、脱氢表雄酮(DHEA)和结合型神经甾体孕烯醇酮硫酸酯(PREGS)、脱氢表雄酮硫酸酯(DHEAS)的含量;RT-PCR方法观察海马神经元P450侧链裂解酶(P450scc)、甾体合成快速调节蛋白(StAR)和3β-羟基甾醇脱氢酶(3β-HSD)等神经甾体合成关键酶基因的mRNA的表达.结果:TO901317激活LXR,促进P450scc,StAR和3β-HSD的mRNA表达,增加海马神经元培养液中神经甾体PREG,DHEA,PREGS和DHEAS含量.结论:LXR激活时,可通过上调海马神经元P450scc,StAR和3β-HSD的mRNA表达,促进神经甾体的合成.

AIM： To investigate the effect of liver X receptor （LXR） activation on the synthesis of neurosteriod in hippocampal neurons. METHODS ： On day 7 of culture, hippocampal neurons were treated with 2.0 μmoL/L TO901317 dissolved in dimethylsulfoxide for 48 h. The mRNA expressions of P450 side chain cleavage （P450scc）, steroidogenic acute regulatory protein （STAR） and 3β-hydroxysteroid dehydrogenase （ 3β-HSD ） were measured by RT-PCR and the contents of unconjugated neurosteriods pregnenolone （PREG） , dehydroepiandrosterone （ DHEA ） and conjugated neurosteroids pregnenolone sulfate（PREGS） , dehydroepiandrosterone sulfate （DHEAS） in medium were analyzed and determined using high-performance liquid chromatography-mass spectrometry （HPLC-MS）. RESULTS： Incubation of hippocampal neurons with TO901317 significantly increased the expressions of P450scc, STAR and 3β-HSD mRNA and the levels of PREG, DHEA, PREGS and DHEAS. CONCLUSION： Activation of LXR contributes to the synthesis of neurosteriod by up-regulating the expressions of P450scc, StAR and 3β-HSD in hippocampal neurons.