宫内生长迟缓和高脂饮食对大鼠血脂及肝脏相关基因转录水平的影响

Effects of intrauterine growth restriction and high-fat diet on serum lipid and transcriptional levels of related hepatic genes in rats

摘要:

目的 探讨宫内生长迟缓(IUGR)和高脂饮食对大鼠生长、脂代谢及肝脏相关基因的作用。方法 采用母鼠孕期全程限食法建立IUGR 大鼠模型。断奶后,将32 只正常子鼠和24 只IUGR 子鼠随机分配到标准饮食组和高脂饮食组。10 周龄时,测量空腹血糖、血脂,观察肝脏组织病理切片,并测定肝脏相关基因转录水平。结果 IUGR 大鼠与正常大鼠比较,10 周龄时,标准饮食下两者体重差异有统计学意义,而高脂饮食下两者体重差异无统计学意义。和正常大鼠相比,两种饮食下的IUGR 大鼠均出现能量摄入增加、空腹血糖、总胆固醇和甘油三酯水平升高。无论在正常大鼠还是IUGR 大鼠,高脂饮食均降低了血清甘油三酯浓度。IUGR和高脂饮食均加重了肝脏的脂肪堆积。双因素方差分析显示,10 周龄时,与正常大鼠比较, IUGR 大鼠肝脏脂代谢相关基因PGC-1α、CPT-1、SREBF-2、HMGR、LDLR 和SREBF-1 的表达差异有统计学意义;与标准饮食比较,高脂饮食增加了正常大鼠和IUGR 大鼠PPARα、SREBF-1、SREBF-2、ABCG5 和CYP7A1 的表达;IUGR 和高脂饮食对LDLR 水平存在交互作用。结论 IUGR 大鼠呈现出高血脂和肝脏脂肪堆积,可能与IUGR 大鼠的食欲增强和转录水平上脂肪酸氧化相关基因调节紊乱有关。高脂饮食可加重大鼠的肝脏脂肪堆积,可能与转录水平上调节脂肪酸合成的相关基因表达增加和甘油三酯分泌减少相关。

Abstract:

Objective To study the effects of intrauterine growth restriction (IUGR) and high-fat diet on the growth, lipid metabolism, and related hepatic genes in rat offspring. Methods The rat model of IUGR was established by food restriction during the entire pregnancy. After weaning, 32 normal rats and 24 offspring rats with IUGR were randomly allocated to standard diet group or high-fat diet group. At the age of 10 weeks, fasting plasma glucose and blood lipid were examined. Additionally, pathological sections for hepatic tissues were observed, and the transcriptional levels of related hepatic genes were measured. Results At the age of 10 weeks, there was a significant difference in body weight between IUGR rats and normal rats on standard diets, but no significant difference in body weight was observed between the two groups on high-fat diets. Compared with the normal rats, IUGR rats showed increased energy intake and increased levels of fasting plasma glucose, total cholesterol, and triglyceride on both standard and highfat diets. High-fat diets reduced the concentration of serum triglyceride in both normal rats and IUGR rats. IUGR and high-fat diets aggravated the fat accumulation in the liver. Two-factor analysis of variance showed that at the age of 10 weeks, the expression of genes related to lipid metabolism in the liver, PGC-1α, CPT-1, SREBF-2, HMGR, LDLR and SREBF-1, differed significantly between IUGR and normal rats. Compared with standard diets, high-fat diets increased the expression of PPARα, SREBF-1, SREBF-2, ABCG5, and CYP7A1 in both normal rats and IUGR rats. IUGR and high-fat diets had an interactive effect on LDLR expression. Conclusions Hyperlipidemia and fat accumulation in the liver observed in IUGR rats may be related to increased appetite and regulation disorder in genes related to fatty acid oxidation at the transcriptional level. High-fat diets may aggravate fat accumulation in the liver in rats, which may be related to increased expression of genes related to regulation of fatty acid synthesis at the transcriptional level and reduction in secretion of triglyceride.