论文部分内容阅读
目的探讨小鼠孕晚期肝脏脂质代谢变化特点,并进一步分析妊娠对小鼠肝脏脂肪酸摄取、从头合成和氧化关键酶基因表达和相应核受体的影响。方法选取孕第17天小鼠和未孕小鼠的血清和肝脏组织。检测空腹血糖、血清和肝脏甘油三酯(TG)、总胆固醇(TCH)和极低密度脂蛋白(VLDL)水平,油红O染色法分析肝脏脂质沉积。实时定量PCR检测肝脏组织相关基因mRNA水平,Western blot检测肝脏组织相关核受体核蛋白水平。结果妊娠晚期小鼠血清、肝脏TG和VLDL含量较未孕鼠均明显升高;油红O染色显示妊娠晚期小鼠肝脏脂质沉积明显;妊娠晚期小鼠肝脏核蛋白孕烷X受体(PXR)明显激活,其靶基因肝脏脂肪酸转位酶(cd36)mRNA水平显著上调;妊娠晚期小鼠肝脏核蛋白固醇调节元件结合蛋白-1c(SREBP-1c)激活,上调靶基因肝脏脂肪酸合成酶(fas)和乙酰辅酶A羧化酶(acc)等mRNA水平;肝脏核蛋白过氧化物酶体增殖物激活受体α(PPARα)明显受抑,下调靶基因肝脏肉碱棕榈酰转移酶1α(cpt1α)、细胞色素P450酶4a10(cyp4a10)和cyp4a14 mRNA水平。结论妊娠可能通过激活PXR上调肝细胞脂肪酸摄取关键酶、激活SREBP-1c上调从头合成脂肪酸关键酶、抑制PPARα下调肝脏脂肪酸氧化关键酶,引起妊娠晚期肝脏脂质合成增加和脂质沉积。
OBJECTIVE: To investigate the characteristics of liver lipid metabolism in mice during the third trimester of pregnancy, and to further analyze the effect of pregnancy on the uptake and de novo synthesis of fatty acid and the expression of key nuclear oxidase genes in mouse liver. Methods The serum and liver tissues of mice and non-pregnant mice on the 17th day of pregnancy were selected. Fasting blood glucose, serum and liver triglyceride (TG), total cholesterol (TCH) and very low density lipoprotein (VLDL) levels were measured. Lipid O staining was used to analyze the lipid deposition in the liver. Real-time quantitative PCR was used to detect the mRNA level of liver tissue related genes, and Western blot was used to detect the nuclear protein level of liver nuclear receptor. Results The levels of serum TG and VLDL in the third trimester of pregnancy were significantly higher than those of the third trimester of pregnant women. The results of oil red O staining showed that the liver lipid deposition in the third trimester of pregnancy was marked. In the second trimester of pregnancy, the nuclear protein pregnane X receptor (PXR ), And its target gene hepatic fatty acid translocase (cd36) mRNA level was significantly up-regulated. The activation of nucleoprotein-1c (SREBP-1c) in the third trimester of pregnancy increased the hepatic fatty acid synthase fas, and acetyl coenzyme A carboxylase (ACP) mRNA levels. Liver nuclear protein peroxisome proliferator-activated receptor α (PPARα) was significantly inhibited and the target gene hepatic carnitine palmitoyl transferase 1α (cpt1α ), Cytochrome P450 enzymes 4a10 (cyp4a10) and cyp4a14 mRNA levels. Conclusion Pregnancy may activate key enzyme of up-regulation of fatty acid uptake in hepatocytes by activating PXR, activate SREBP-1c up-regulates key enzyme of de novo synthesis of fatty acid, inhibit PPARα down-regulation of hepatic fatty acid oxidation, and cause lipid synthesis and lipid deposition in liver during late pregnancy.