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贝特类药物在大鼠肝脏中对硬脂酰辅酶 A 去饱和酶 1 和 2 基因的差异诱导。

Differential induction of stearoyl-CoA desaturase 1 and 2 genes by fibrates in the liver of rats.

机构信息

Faculty of Pharmaceutical Sciences, Josai University, 1–1 Keyakidai, Sakado, Saitama 350–0295, Japan.

出版信息

Biol Pharm Bull. 2012;35(1):116-20. doi: 10.1248/bpb.35.116.

Abstract

The administration of fibrates (fenofibrate, bezafibrate and clofibric acid) to rats induced stearoyl-CoA desaturase (SCD) in the liver, and increased relative expression of mRNAs encoding SCD1 and SCD2 in dose- and time-dependent manners. The magnitudes of the increases in SCD2 mRNA level caused by fenofibrate and clofibric acid were much higher than those of SCD1 at relatively higher doses of the fibrates, and a relatively long time (7 or 14 d) was required for significant induction of SCD2 mRNA expression compared with that of SCD1. Although the absolute number of transcripts for SCD2 was 1,800 times lower than that of SCD1 in the control liver, it was strikingly increased by fibrates. These results suggest that differential regulations operate for the gene expression between SCD1 and SCD2, and that the physiological significance of SCD2 is distinct from that of SCD1 in the liver.

摘要

给予大鼠应用贝特类药物(非诺贝特、苯扎贝特和氯贝酸),可诱导肝脏中硬脂酰辅酶 A 去饱和酶(SCD)的产生,并呈剂量和时间依赖性增加编码 SCD1 和 SCD2 的 mRNAs 的相对表达。与 SCD1 相比,非诺贝特和氯贝酸引起的 SCD2 mRNA 水平增加幅度在相对较高的贝特剂量时要高得多,并且与 SCD1 相比,SCD2 mRNA 表达的显著诱导需要相对较长的时间(7 或 14d)。尽管在对照肝脏中 SCD2 的转录本绝对数量比 SCD1 低 1800 倍,但贝特类药物可显著增加 SCD2 的表达。这些结果表明,SCD1 和 SCD2 之间的基因表达存在不同的调控机制,并且 SCD2 在肝脏中的生理意义不同于 SCD1。

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