宫内轻度高糖暴露及出生后高脂饮食对子鼠体质量和脂代谢的远期影响

摘要

目的 通过建立孕鼠宫内轻度高糖环境模型,探讨宫内轻度高糖暴露及出生后高脂饮食对子鼠体质量和脂代谢的远期影响.方法 21只Wistar孕鼠随机分为高糖组(14只)和对照组(7只),高糖组孕鼠一次性腹腔注射20％的链脲佐菌素25 mg/kg,诱导宫内轻度高糖环境模型；对照组孕鼠以同样方法仅行腹腔注射等体积的柠檬酸-柠檬酸钠缓冲液.将其子鼠分为高糖环境正常饮食(DN)组,高糖环境高脂饮食(DF)组,对照正常饮食(CN)组,对照高脂饮食(CF)组.记录两组孕鼠的血糖水平和4组子鼠出生后体质量变化,测定28周龄时各组子鼠肠系膜、附睾和肾周等内脏脂肪含量以及甘油三酯(TG)和高密度脂蛋白(HDL-C)水平.结果 (1)高糖组孕鼠孕期平均血糖水平为(16.6±3.4) mmol/L,显著高于对照组的(5.8 ±1.1) mmol/L,两组比较,差异有统计学意义(P＜0.01).(2) CN组子鼠在出生时、3周龄、4周龄时的体质量分别为(6.6±0.5)、(35.6±4.4)、(71.5±6.8)g,DN组子鼠分别为(7.4±0.6)、(44.1±5.9)、(79.6±7.4)g,DF组子鼠分别为(7.4±0.2)、(43.9 ±6.9)、(76.1 ±5.8)g,DN组及DF组均明显高于CN组,分别比较,差异均有统计学意义(P＜0.05)；CF组子鼠分别为(6.7±0.5)、(33.0±6.5)、(66.1±10.2)g,与CN组比较,差异均无统计学意义(P＞0.05).(3)超过4周龄以后,直至28周龄时,各组子鼠体质量增长均呈增高趋势,但各组分别比较,差异均无统计学意义(P＞0.05).(4)DN组、CF组和DF组的子鼠肾周脂肪含量分别为(13.8±3.3)、(14.3±3.2)、(18.4±1.3)g,均明显高于CN组的(9.7±3.5)g,分别比较,差异均有统计学意义(P＜0.05);CF组和DF组的子鼠附睾脂肪含量均明显高于CN组,分别比较,差异也均有统计学意义(P＜0.05).各组子鼠肠系膜脂肪含量分别比较,差异均无统计学意义(P＞0.05).(5)DN组、CF组和DF组的子鼠TG水平分别为(0.52 ±0.14)、(0.52±0.09)、(0.54±0.17) mmol/L,明显高于CN组的(0.41 ±0.09) mmol/L,分别比较,差异有统计学意义(P＜0.05),但前3组之间分别比较,差异均无统计学意义(P＞0.05)；各组子鼠HDL-C分别比较,差异均无统计学意义(P＞0.05).结论 宫内轻度高糖环境下,子鼠出生时和生后早期存在体质量增长过快的趋势,远期出现内脏脂肪含量增多和脂代谢紊乱的情况,出生后高脂饮食使这些代谢紊乱进一步加重.%Objective To investigate the long-term effects of intrauterine mild hyperglycemia exposure and postnatal high fat diet on the body weight and metabolism of offspring through a pregnant rat model of intrauterine mild hyperglycemia.Methods Twenty-one pregnant Wistar rats were randomly divided into intrauterine hyperglycemia group and control group.Twenty percent streptozotocin (STZ,25 mg/kg)was given to rats of intrauterine hyperglycemia group by a single intraperitoneal injection to induce intrauterine mild hyperglycemia; control group rats received an equal volume of citric acid-sodium citrate buffer.Off springs were divided into 4 groups:exposed to intrauterine hyperglycemia and fed with normal diet group(group DN)or high fat diet group (group DF) ; exposed to intrauterine euglycemia and fed with normal diet group(group CN)or high fat diet group(group CF).The blood glucose levels of pregnant rats in two groups and body weights of offsprings in four groups were recorded.At the age of 28 weeks,the mesenteric fat amount,epididymal amount,perirenal fat amount,total triglyceride (TG)and high density 1 ipoprotein-cholestrol(HDL-C) were measured in all four groups.Results (1) The average blood glucose level of intrauterine hyperglycemia group[(16.6 ± 3.4) mmol/L] was significantly higher than that of the control group [(5.8 ± 1.1) mmol/L,P ＜ 0.01].(2) On the birth day,3 weeks and 4 weeks,the body weight of group DN [(7.4 ± 0.6),(44.1 ± 5.9),(79.6 ± 7.4) g] and group DF [(7.4 ± 0.2),(43.9 ±6.9),(76.1 ± 5.8) g] were remarkably increased compared with group CN [(6.6 ± 0.5),(35.6 ± 4.4),(71.5±6.8) g,P＜0.05]; but the body weight in group CF [(6.7 ±0.5),(33.0 ±6.5),(66.1 ±10.2) g] had no statistical difference compared with group CN(P ＞ 0.05).(3)From then on,the bodyweights of the offsprings in four groups presented an increasing trend,but there was no statistical difference until 28 weeks(P ＞0.05).(4) The perirenal fat amount of group DN,group CF and group DF [(13.8 ±3.3),(14.3 ± 3.2),(18.4 ± 1.3) g] were remarkably increased compared with group CN [(9.7 ± 3.5) g,P ＜ 0.05] ; the epididymal fat amount of group CF and group DF were also significantly increased compared to group CN(P ＜ 0.05) ; the mesenteric fat amount in four groups had no statistical difference (P ＞ 0.05).(5) The TG level of group DN,group CF and group DF[(0.52 ±0.14),(0.52 ±0.09),(0.54 ±0.17)mmol/L] were significantly higher compared to group CN [(0.41 ± 0.09) mmol/L,P ＜ 0.05],but there was no statistical difference within the first three groups (P ＞ 0.05) ; the HDL-C level in four groups had no statistical difference(P ＞ 0.05).Conclusions In intrauterine mild hyperglycemia environment,there were some evidently metabolic changes observed in the offspring,including body weight increasing on birth day and early postnatal period,visceral fat amount increasing and lipid metabolism disorders,which could be aggravated by postnatal high fat diet.