肝X受体激动剂对C57/BL6小鼠大脑C型1类尼曼-匹克蛋白表达的影响

Effects of Liver X receptor agonist on the expression of Niemann-Pick C1 protein in the brain of C57/BL6 mice

目的:研究肝X受体(LXR)激动剂T0901317对C57/BL6小鼠大脑C型1类尼曼-匹克蛋白(NPC1)表达和胆固醇流出的影响。方法:C57/BL6小鼠被随机分成3组,对照组(n=13)给予赋型剂灌胃;处理1组(n=13)给予T0901317(10mg/kg)灌胃;处理2组(n=13)给予T0901317(20mg/kg)灌胃。通过高效液相色谱法测定大脑胆固醇含量;采用逆转录聚合酶链反应、蛋白质印迹和免疫组化方法分别检测大脑组织NPC1mRNA和蛋白质表达。结果:两处理组小鼠大脑胆固醇含量明显少于对照组(P<0.05),其NPC1mRNA和蛋白质表达较对照组明显增高(P<0.05)。结论:T0901317减少大脑胆固醇含量可能与其上调NPC1表达有关。

Objective To investigate the effects of Liver X receptor （LXR） agonist T0901317 on the expression of Niemann-Pick C1 protein （NPC1） and cholesterol efflux in the brain of C57/BL6 mice. Methods C57/BL6 mice were randomly divided into three groups：control group （n = 13）,treatment group 1 （n = 13） and treatment group 2（n = 13）. Control group and treatment groups were treated with vehicle,T0901317 （10 mg/kg and 20 mg/kg） daily by oral gavage respectively. Cholesterol level in the brain was measured by high performance liquid chromatography. And the expression of NPC1 in the brain was analyzed by reverse transcriptase-polymerase chain reaction（RT-PCR）,immunohistochemistry and western blotting. Results Compared to the control group,cholesterol levels in the brains of both T0901317 treated groups were significantly decreased（P〈 0.05）,and the expression of NPC1 in the brain of both treated groups were up-regulated （P 〈0.05）. Conclusion T0901317 treatment reduces cholesterol level in the brain of C57/BL6 mice,which maybe related to the upregulated expression of NPC1.