单次口服瑞舒伐他汀对国人健康受试者外周白细胞基因表达的影响

Effect of a single dose of rosuvastatin administration on peripheral blood cells gene expression in Chinese volunteers

目的:观察单次口服20 mg瑞舒伐他汀对国人健康志愿者血脂和外周白细胞基因表达的影响,探讨瑞舒伐他汀的早期效应的作用机理。方法:30名健康男性受试者单次晨起空腹口服瑞舒伐他汀20 mg。用寡核苷酸微阵列基因表达芯片筛检服药72 h后外周白细胞的差异表达基因。然后用RT-PCR验证其中4个差异表达基因(ATM,CASP8,IL8RB和S100B)的mRNA表达改变。同时还测定服药前、服药72h后血脂、血清高敏C反-应蛋白和血浆纤维蛋白原。结果:服药72 h后基因表达芯片筛选到外周白细胞有明显表达差异的基因24个,其功能涉及细胞因子、受体的相互作用及凋亡信号通路等。其中ATM,CASP8,IL8RB和S100B基因差异的表达的结果得到RT-PCR方法的验证。口服瑞舒伐他汀20 mg使健康受试者的血清低密度脂蛋白胆固醇下降23.8%[(0.54±0.34)mmo.lL-1;P=0.000];但对血清高密度脂蛋白胆固醇、三酰甘油和高敏C反-应蛋白和血浆纤维蛋白原均无影响。结论:瑞舒伐他汀具有快速的降脂作用,疗效可能与外周白细胞基因差异表达有关。

Objective： To investigate the acute effects of rosuvastatin on lipids profile and gene expression of peripheral leukocytes following a single dose of rosuvastatin therapy.Methods： Thirty healthy Chinese male volunteers were enrolled.The serum lipids,high-sensitivity C-reactive protein,and plasma fibrinogen were determined before and 72 h after a single dose of 20 mg rosuvastatin.The differentially expressed genes of peripheral leukocytes after rosuvastatin administration were screened by human oligonucleotide microarray expression chips.Then the mRNA levels of four differentially expressed genes of ATM,CASP8,IL8RB and S100B were identified by RT-PCR.Results： Rosuvastatin decreased both serum total cholesterol and low density lipoprotein cholesterol significantly at 72 h following a single dose of 20 mg rosuvastatin administration.However,no significant changes occurred in blood high-density lipoprotein cholesterol,triglycerides,C-reactive protein and fibrinogen after treatment.A total of 24 genes were differentially expressed after treatment.Their function involved important cell biological processes such as cytokine-cytokine receptor interaction,and apoptosis signaling pathway.The expression levels of ATM,CASP8,IL8RB and S100B measured by RT-PCR agreed with those by microarray,thus confirmed that the expression of these genes were changed by rosuvastatin.Conclusion： Rosuvastatin rapidly decreased the serum cholesterol as well as affected the gene expression of peripheral leukocytes in healthy volunteers.It may provide us some new clues for further studies on its potential pleitropic effects.