外科理论与实践Issue(5)：412-417,6.DOI:10.16139/j.1007-9610.2015.05.012
PDZK1对成石喂养小鼠肝脏SRB1调节作用的研究
Regulation of hepatic SRB1 expression by PDZK1 in mice fed with lithogenic diet
摘要
Abstract
Objective To investigate the expression of genes involving in hepatic lipid metabolism in mice fed with lithogenic diet and the regulation of hepatic scavenger receptor B type 1 (SRB1) by PDZ domain-containing 1 (PDZK1) protein. Methods Male C57BL/6J mice were fed with lithogenic diet and the differences in the expression of hepatic genes were studied. PDZK1-overexpressing lentivirus vector and small interfering RNA adenovirus vector were constructed and were used to infect C57BL/6J mice fed with lithogenic diet. mRNA expression of the genes involved in lipid metabolism in liver was quantified by real-time PCR. The protein levels of PDZK1 and SRB1 were determined by Western blot. Results The mRNA expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key enzyme in cholesterol synthesis, in-creased (P<0.01) in the mice fed with lithogenic diet for 4 weeks. However the expression of cholesterol 7-αhydroxylase, the rate-limiting enzyme of bile acid synthesis, decreased significantly (P<0.001). Both the mRNA expression of SRB1 and PDZK1 decreased under lithogenic diet (P<0.001). Intraperitoneal injection to mice with PDZK1-overexpressing lentivirus increased the hepatic PDZK1 protein 37% (P<0.01) after 4 weeks fed with lithogenic diet. The increased expression of SRB1 protein was found in the liver plasma membrane (+136%, P<0.05) but not in the whole liver lysates. On contrary, the intraperitoneal injection to the mice with SiPDZK1 adnovirus after feeding with lithogenic diet 2 weeks reduced PDZK1 protein 49%(P<0.05). In accompany, the total SRB1 protein of liver increased 60%(P<0.05) and SRB1 protein in hepatic membrane decreased 14%. Conclusions Lithogenic diet changed the expression of hepatic genes in lipids metabolism in mice. The down-regulation of SRB1 might be due to the suppression of PDZK1 expression. Intervention of hepatic PDZK1 expression could affect the expression of SRB1 protein in the membrane of hepatocytes.关键词
肝脏/PDZK1/B族Ⅰ型清道夫受体/成石饲料Key words
Liver/PDZK1/Scavenger receptor B type 1/Lithogenic diet分类
医药卫生引用本文复制引用
蔡强,吴健,蔡劬,吴卫泽,韩天权,蒋兆彦..PDZK1对成石喂养小鼠肝脏SRB1调节作用的研究[J].外科理论与实践,2015,(5):412-417,6.基金项目
国家自然科学基金 （）
