生命早期使用头孢曲松对生命后期高脂饲料负荷小鼠糖脂代谢的影响

Effects of oral administration of ceftriaxone in early life on glucolipid metabolism of high fat diet-induced mice

目的探究生命早期使用抗生素对生命后期高脂饲料负荷下的小鼠血糖、血脂等糖脂代谢指标的影响。方法将48只2周龄雌性BALB/c小鼠随机分为空白对照组、抗生素组、高脂组和联合作用组,每组12只,抗生素组和联合作用组以100 mg/kg头孢曲松灌胃,其余2组灌胃等量生理盐水,持续至4周龄后停止灌胃,接着高脂组和联合作用组以高脂饲料、其余2组以普通饲料喂养12周。最后1周测定空腹血糖并进行口服糖耐量实验,实验结束后测定血脂、肝脏脂质、胰岛素和瘦素水平,并计算胰岛素抵抗指数。结果与普通饲料相比,高脂饲料引起小鼠糖耐量受损,内脏脂肪、血糖、胰岛素抵抗指数、血脂、肝脏脂质和瘦素增加(P<0.05);与空白对照组相比,抗生素组小鼠糖耐量受损,内脏脂肪、血糖和肝脏甘油三酯水平增加(P<0.05);与高脂组相比,联合作用组小鼠的糖耐量受损、血糖、胰岛素抵抗指数和肝脏总胆固醇水平增加(P<0.05)。结论生命早期使用头孢曲松增加了机体内脏脂肪、血糖、胰岛素抵抗和肝脏脂质,且加剧了高脂饲料诱导的糖脂代谢紊乱,表明生命早期使用抗生素可能会提高机体对高脂饲料诱导糖脂代谢异常的易感性。

OBJECTIVE This study aimed to explore whether exposure to ceftriaxone during early life could influences glucose and lipid metabolism of high fat diet-induced mice. METHODS Total 48 of female BALB/c aged 2 week old were randomly divided into control group(treated with saline),antibiotic group(treated with100 mg/kg ceftriaxone), high-fat diet group(treated with saline) and combined action group(treated with 100 mg/kg ceftriaxone)(n=12), respectively to stop gavage 2 weeks later. Then high-fat diet group and combined action group were fed with high-fat diet for 12 weeks. Fasting blood glucose(FBG) and oral glucose tolerance test were conducted in the last week. Serum total cholesterol(TC), triglyceride(TG), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), fasting insulin, leptin and TG, TC in liver were also measured. Furthermore, homeostasis model assessment of insulin resistance(HOMA-IR) was calculated from FBG and insulin. RESULTS Compared with normal chow diet, high-fat diet impaired oral glucose tolerance and increased the levels of abdominal adipose tissue, FBG, HOMA-IR, lips in serum and liver and leptin(P<0.05).The oral administration of ceftriaxone in early life impaired oral glucose tolerance and increased the levels of abdominal adipose tissue, FBG and TG in liver(P<0.05). In addition, early ceftriaxone intervention could enhance the impaired glucose tolerance, the increasing FBG, insulin resistance and liver lipids associated with high-fat diet(P<0.05). CONCLUSION Early ceftriaxone intervention not only significantly increases the level of abdominal adipose tissue, FBG, insulin resistance and liver lipids, but also enhances glycolipid metabolic disorders induced by high-fat diet. These result suggest that the exposure to antibiotics in the early life might increase the sensitivity of host animal to high fat diet induced abnormal glycolipid metabolism late.