Kojima Misaki, Degawa Masakuni
Laboratory of Animal Gene Function, Department of Physiology and Genetic Regulation, Institute of Insect and Animal Sciences, National Institute of Agrobiological Sciences, Tsukuba, Ibaraki, Japan.
J Appl Toxicol. 2006 Jul-Aug;26(4):381-4. doi: 10.1002/jat.1138.
Changes in gene expression levels of hepatic sterol regulatory element binding protein-2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) after a single i.v. injection of lead nitrate (LN, 100 micromol kg(-1) body weight) were examined comparatively by real time reverse transcriptase-polymerase chain reaction (RT-PCR) in male and female rats. Significant increases in the gene expression level of SREBP-2, a transcription factor for the HMGR gene, occurred at 6-12 h in male and at 24-36 h in female rats after LN-treatment. The gene expression level of HMGR, a rate-limiting enzyme for cholesterol biosynthesis, significantly increased at 3-48 h in male rats and 12-48 h in female rats. Subsequently, significant increases in the amount of hepatic total cholesterol in male and female rats were also observed at 3-48 h and 24-48 h, respectively. The present findings demonstrate that increases in gene expressions of hepatic SREBP-2 and HMGR and the amount of hepatic total cholesterol by LN occur earlier in male rats than in the females, and that increases in the gene expression level of HMGR and the amount of hepatic total cholesterol occur prior to the increase in the gene expression level of SREBP-2 in either sex of rats.
通过实时逆转录聚合酶链反应（RT-PCR）比较研究了单次静脉注射硝酸铅（LN，100微摩尔/千克体重）后，雄性和雌性大鼠肝脏中固醇调节元件结合蛋白-2（SREBP-2）和3-羟基-3-甲基戊二酰辅酶A还原酶（HMGR）基因表达水平的变化。在LN处理后，雄性大鼠在6至12小时、雌性大鼠在24至36小时时，HMGR基因的转录因子SREBP-2的基因表达水平显著增加。胆固醇生物合成的限速酶HMGR的基因表达水平在雄性大鼠3至48小时、雌性大鼠12至48小时时显著增加。随后，分别在雄性和雌性大鼠的3至48小时和24至48小时时也观察到肝脏总胆固醇量显著增加。本研究结果表明，LN导致的肝脏SREBP-2和HMGR基因表达增加以及肝脏总胆固醇量增加在雄性大鼠中比雌性大鼠更早出现，并且在大鼠的两种性别中，HMGR基因表达水平和肝脏总胆固醇量的增加均先于SREBP-2基因表达水平的增加。
