目的 探讨嘌呤类生物碱1，3，7，9-四甲基尿酸（Theacrine）对Sirtuin3（SIRT3）调节的脂肪酸代谢相关基因的影响。方法 对3T3-L1前脂 肪细胞进行诱导分化，并在诱导的第5天对细胞培养液中加入不同浓度的Theacrine孵育，采用实时荧光PCR（RT-PCR）方法测定细胞内SIRT3及脂肪酸代谢相关基因的表达。 并对正常小鼠灌胃给予低、中、高剂量的Theacrine（10，20，40 mg·kg-1）及Caffeine（20 mg·kg-1）1h后，采用RT-PCR测定小鼠肝脏组织、棕色脂肪组织中SIRT3及脂 肪酸代谢相关基因LCAD、ATP5c、UCP1、HTGL、FABP4等基因的表达，同时采用Western Blotting检测肝脏中SIRT3的蛋白表达。 结果 与正常对照组比较，Theacrine可以上 调3T3-L1前脂肪细胞在分化过程中SIRT3、LCAD、FABP4、LPL的表达。低剂量的Theacrine可显著上调小鼠肝脏中SIRT3基因，高剂量则表现为抑制作用，与其蛋白表达结果一 致。同时，低、高剂量的Theacrine分别显著提升及抑制小鼠肝脏中LCAD、FABP4、HTGL、ATP5c等基因表达。此外，低剂量的Theacrine对小鼠棕色脂肪中SIRT3、LCAD等基因 表达的影响不大，但显著上调了UCP1的基因表达。结论 一定剂量的Theacrine能调节相关基因影响脂肪酸代谢，该作用可能与其上调SIRT3的表达相关。

Objective To observe the effects of 1，3，7，9-tetramethyl uric acid（theacrine） on fatty acid metabolism related gene regulated by Sirtuin 3（SIRT3）. Methods On the fifth day of the induction of 3T3-L1 preadipocyte differentiation，various concentrations of theacrine were added into the culturing solution. RT-PCR was used to detect SIRT3 and fatty acid metabolism related genes expression in 3T3-L1 cells during differentiation. In in-vivo experiment，normal mice were given intragastric administration of 10，20，40 mg/kg of theacrine，20 mg/kg of caffeine， respectively. One hour after later，gene expression levels of LCAD，ATP 5c，UCP1，HTGL and FABP4 in mice hepatic tissue and brown adipose tissue were investigated by RT-PCR，and SIRT3 protein expression in the hepatic tissue was also detected by using Western blotting method. Results In vitro experiment showed that theacrine could activate SIRT3. Compared with the blank control group，theacrine could up-regulate SIRT3，LCAD，FABP4 and LPL gene expression levels obviously during the differentiation of 3T3-L1 preadipocyte. Theacrine（10 mg/kg） could up-regulate SIRT3 gene expression in the liver，but 40 mg/kg of theacrine showed inhibition on SIRT3，the results being in accordance with those obtained by Western blotting method. Low- dose theacrine（10 and 40 mg/kg） could up-regulate hepatic LCAD，FABP4，HTGL and ATP5c mRNA expression to various degrees，while high-dose theacrine（ 40 mg/kg） could down-regulate their levels. Moreover，low-dose theacrine had no obvious effects on SIRT3 and LCAD gene expression levels in the brown adipose tissue，but could obviously up-regulate UCP1 mRNA expression. Conclusion Theacrine at certain dosage has an effect on fatty acid metabolism through regulating fatty acid metabolism related gene，and the mechanism may be related with the up-regulation of SIRT3 expression.

R285.5

国家自然科学基金资助项目（81102485）；广东省自然科学基金项目（20120011316）；辽宁省科技厅项目（201202129）。