Objective: To study the effect of epigallocatechin-3-gallate (EGCG) on liver lipid metabolism in rats with intrauterine growth restriction (IUGR) and related mechanism.
Methods: A rat model of IUGR was established by food restriction during entire pregnancy, and then the rats were randomly divided into an IUGR group and an EGCG group (n=8 each). The rats in the EGCG group were fed with water containing EGCG from after weaning to 10 weeks. Eight pup rats born from the pregnant maternal rats without food restriction were used as the control group. At the age of 13 weeks, body weight was measured. Blood and liver tissue samples were collected to measure fasting total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), fasting plasma glucose (FPG), fasting insulin (FINS), and liver lipids. Homeostasis model assessment of insulin resistance (HOMA-IR) and adipose insulin resistance (adipo-IR) were calculated. Pathological sections of the liver were observed and quantitative real-time PCR was used to measure the mRNA expression of related genes in the liver.
Results: At the age of 13 weeks, there was no significant difference in body weight between groups (P=0.067). There were significant differences between groups in FPG, FFA, FINS, HOMA-IR, and adipo-IR (P<0.05). There were no significant differences in the serum levels of TC and TG between groups (P>0.05), while the IUGR group had significantly higher levels of TC and TG in the liver than the EGCG group (P<0.05). Oil red staining showed that the IUGR group had a significant increase in hepatic lipid accumulation, while the EGCG group had certain improvement after EGCG treatment. PCR results suggested that compared with the control group, the IUGR group had significant reductions in the mRNA expression of Ampk and Adipor1 and a significant increase in the mRNA expression of Srebf1 (P<0.05), while EGCG increased the mRNA expression of Ampk and reduced the mRNA expression of Srebf1, with no significant differences in the two indices between the EGCG and control groups (P>0.05).
Conclusions: Early EGCG intervention can down-regulate the de novo synthesis of fatty acids through the Ampk/Srebf1 signaling pathway and reduce hepatic lipid accumulation in IUGR rats by improving insulin resistance of hepatocytes.
目的: 探讨表没食子儿茶素-3-没食子酸酯（EGCG）对宫内生长受限（IUGR）大鼠肝脏脂代谢的影响和机制。
方法: 采用母鼠孕期全程限食法建立IUGR大鼠模型，随机分为IUGR组和EGCG组，EGCG组大鼠在离乳后用含EGCG的饮用水喂养至10周，同时设立正常对照组，每组8只。13周龄时，测量各组大鼠体重后，采集大鼠血液及肝脏组织标本，检测各组大鼠血清空腹总胆固醇（TC）、甘油三酯（TG）、游离脂肪酸（FFA）、血糖（FPG）、胰岛素（FINS）和肝脏脂质水平，计算稳态模型评估胰岛素抵抗（HOMA-IR）和脂肪组织胰岛素抵抗（adipo-IR），观察肝脏组织病理切片，并采用实时荧光定量PCR法检测肝脏相关基因的相对表达水平。
结果: 13周龄时，各组大鼠体重比较差异无统计学意义（P=0.067）。各组间的FPG、FFA、FINS、HOMA-IR和adipo-IR水平比较差异均有统计学意义（P < 0.05）。各组间的血清TC和TG水平比较差异无统计学意义（P > 0.05），但在肝脏中IUGR组TC和TG水平均明显高于EGCG组（P < 0.05）。油红染色结果提示，IUGR大鼠的肝脏脂肪储积明显增加，而EGCG能够改善该现象。PCR结果显示，与对照组相比，IUGR组的Ampk mRNA及Adipor1 mRNA表达水平降低，Srebf1 mRNA表达水平增加（P < 0.05），EGCG能逆转IUGR大鼠Ampk mRNA及Srebf1 mRNA的表达水平，且与对照组比较差异无统计学意义（P > 0.05）。
结论: 早期EGCG干预可能通过Ampk/Srebf1通路下调脂肪酸的从头合成，并通过改善肝细胞的胰岛素抵抗，从而降低IUGR大鼠的肝脏脂肪积累。