围产期壬基酚暴露致子代成年雄性大鼠糖脂代谢紊乱及机制研究

目的探讨围产期壬基酚(nonylphenol,NP)暴露导致成年雄性仔鼠糖脂代谢紊乱及其机制。方法将32只健康成年SPF级SD妊娠大鼠随机分为普通饲料对照(玉米油)组、普通饲料+NP(200 mg/kg)组、高脂高糖饲料(15%猪油、20%白糖、65%普通饲料)对照组、高脂高糖饲料+NP(200 mg/kg)组,每组8只。母鼠从妊娠第6天至产后21 d(PND21,断乳)清晨空腹灌胃染毒NP,染毒容量为5 ml/kg,每天1次。每组随机选取10只雄性仔鼠,于出生70 d后检测胰腺组织中NP、血糖及血清中甘油三酯(triglycerides,TG)、总胆固醇(total cholesterol,TC)的水平,并检测胰腺糖代谢相关基因葡萄糖激酶(glucokinase,GCK)和葡萄糖转运蛋白-2(glucose transporter-2,GLUT-2)及脂肪细胞分化关键基因过氧化物酶体增殖物激活受体γ(peroxisome proliferator activated receptorγ,PPARγ)和脂肪酸合成酶(fatty acid sythase,FAS)的表达水平。结果与普通饲料对照组比较,第4、6周高脂高糖饲料对照组和高脂高糖饲料+NP组仔鼠的体重均大于普通饲料对照组,差异有统计学意义(P0.05)。第8周时,高脂高糖饲料+NP组仔鼠高脂高糖饲料对照组普通饲料对照组(P0.05),且高脂高糖饲料+NP组仔鼠高脂高糖饲料对照组普通饲料+NP组(P0.05)。与普通饲料对照组比较,普通饲料+NP组及高脂高糖饲料+NP组仔鼠的胰腺NP、血糖及血清TG、TC水平均增高,差异有统计学意义(P0.05)。高脂高糖饲料+NP组仔鼠的胰腺NP、血糖及血清TG、TC水平均高于普通饲料+NP组(P0.05)。各组仔鼠胰腺GCK、GLUT-2基因的表达水平依次为高脂高糖饲料+NP组普通饲料+NP组、高脂高糖饲料对照组普通饲料对照组,差异均有统计学意义(P0.05)。各组仔鼠脂肪细胞PPARγ、FAS基因的表达水平依次为高脂高糖饲料+NP组普通饲料+NP组高脂高糖饲料对照组普通饲料对照组,除普通饲料+NP组与高脂高糖饲料对照组比较的FAS基因外,差异均有统计学意义(P0.05)。结论围产期NP暴露可导致仔鼠糖脂代谢紊乱,其机制可能与NP促进胰腺糖代谢和脂肪细胞分化关键基因表达有关。

Effects of perinatal exposure to nonylphenol on glucolipid metabolism disorder in newborn male rats and its pathogenesis

Objective To understand the pathogenesis on glucolipid metabolism disorder in newborn male rats with perinatal exposure to nonylphenol.Methods A total of 32 SD pregnant rats were randomly divided into four groups,normal diet control group(corn oil),normal diet+NP(200 mg/kg body weight) group,high-fat and high-sucrose(HFHS) diet control group and HFHS diet+NP (200 mg/kg body weight) group,the treatments were conducted through gavage.Ten male newborn rats were selected randomly in each group and adipose tissues were weighed and body fat mass index were calculated at the 70th day after birth.Concentrations of NP in pancreatic tissues were measured by HPLC,key genes of glucose metabolism expression and adipocyte differentiation were detected by RT-PCR.The pancreatic tissues were stained with hematoxylin/eosin.The levels of blood glucose and lipids were tested by automatic biochemical analyzer.Results The body weights in HFHS diet control group and HFHS diet +NP group were higher than that in normal diet control group at the 4th,6th week (P＜0.05),and the body weight in HFHS diet +NP group ranked the first at the 8th week.The levels of blood glucose,triglycerides,total cholesterol and the concentration of NP in pancreatic tissues in normal diet +NP group and HFHS diet +NP group were significantly higher compared with those in normal diet control group (P＜0.05).The levels of blood glucose,triglycerides,total cholesterol and the concentration of NP in pancreatic tissues in HFHS diet +NP group were significandy higher compared with those in normal diet+NP group (P＜0.05).The gene expression of GCK and GLUT-2 in pancreatic tissues ranked as HFHS diet+NP group＞normal diet+NP group and HFHS diet control group＞normal diet control group,which showed significantly difference (P＜0.05).The relative expression levels of PPARγ and FAS gene ranked as HFHS diet+NP group＞normal diet+NP group＞HFHS diet control group＞normal diet control group,which showed significantly difference (P＜0.05),except for the comparison between normal diet+NP group and HFHS diet control group.Conclusion Perinatal exposure to NP may increase blood glucose and lipid in adult male rats by changing key gene expression on glucose metabolism and adipocyte differentiation.