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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 observe the effect of single oral administration of 20 mg rosuvastatin on the gene expression of serum lipids and peripheral white blood cells in Chinese healthy volunteers, and to explore the mechanism of the early effect of rosuvastatin. Methods: Thirty healthy male subjects were orally given rosuvastatin 20 mg once daily in the morning. Differentially expressed genes of peripheral white blood cells were screened 72 h after treatment with oligonucleotide microarray gene expression chips. The mRNA expression of four differentially expressed genes (ATM, CASP8, IL8RB and S100B) was then verified by RT-PCR. At the same time also measured before taking the medication 72h after the blood lipids, serum high-sensitivity C-anti-protein and plasma fibrinogen. RESULTS: Twenty-four hours after the treatment, 24 genes whose expression was significantly different in peripheral white blood cells were screened by gene expression chips, and their functions involved in the interaction of cytokines, receptors and apoptosis signaling pathways. The results of RT-PCR analysis of the differences in the expression of ATM, CASP8, IL8RB and S100B genes were obtained. Oral rosuvastatin 20 mg decreased serum LDL-cholesterol by 23.8% ([(0.54 ± 0.34) mmo.L-1; P = 0.000] in healthy subjects; but did not affect serum HDL-cholesterol, Glycerol and high-sensitivity C-anti-protein and plasma fibrinogen had no effect. Conclusion: Rosuvastatin has a rapid lipid-lowering effect, which may be related to the differential expression of peripheral leukocyte genes.