围产期高脂高糖孕鼠NP暴露对仔鼠肥胖的影响及机制探讨

发布时间：2019-06-06 05:40

【摘要】：目的观察围产期高脂高糖孕鼠壬基酚(NP)暴露对子代体质量、脂肪生成及脂肪细胞分化基因、肝脏和脂肪细胞变化的影响,探讨在围产期高脂高糖饮食基础上NP暴露对仔鼠肥胖的作用机制。方法选择SD大鼠雌性40只、雄性20只合笼交配,收集交配成功的孕鼠,随机分为普通饲料对照组(OC组)、高脂高糖饲料对照组(HC组)、高脂高糖饲料+NP低剂量组(HNL组)、高脂高糖饲料+NP高剂量组(HNH组)各10只。普料OC组食用普通饲料,HC组、HNL组、HNH组均食用高脂高糖饲料。从母鼠受孕第6天到产后第21天,OC组、HC组孕鼠均予玉米油0.5 m L/(kg·d)灌胃,HNL组、HNH组分别予NP 50、100 mg/(kg·d)灌胃。仔鼠出生后正常进行母乳喂养,断乳后均以普通饲料喂养至70 d。干预70 d后,取仔鼠腹主动脉血,采用全自动生化分析仪检测血清TG、TC、HDL及LDL水平。取血前称仔鼠体质量,取血后取性腺旁脂肪垫测脂肪质量,计算脂肪系数。取仔鼠肝脏组织,采用Real Time PCR法检测调控脂肪细胞分化的关键基因转录调节因子(CEBP-α)、固醇调节结合蛋白(SREBP-1)、过氧化物酶体增殖物激活受体γ(PPARγ)mRNA的表达。取仔鼠肝脏组织和性腺旁脂肪组织,采用HE染色法观察肝脏细胞和脂肪细胞形态。结果 HNL组、HNH组血清TG、TC、LDL均高于HC组(P均0.01)。HNL组、HNH组体质量、脂肪系数均高于HC组,HNH组脂肪质量高于HC组(P均0.01)。HNH组CEBP-αmRNA表达高于OC组(P0.01)。HNH组的SREBP-1、PPARγmRNA表达均高于HC组(P均0.01)。HE染色示,HC组可见部分肝脏细胞脂肪变性,HNL组可见大量肝细胞脂肪样变,HNL组可见肝细胞广泛气球样变和大量脂滴;HC组部分脂肪细胞面积增大,HNL组大部分脂肪细胞面积明显增大。结论围产期高脂高糖孕鼠NP联合暴露可增加仔鼠体质量、脂肪质量、血脂含量,导致肝脏脂肪样和脂肪细胞增大增多,其机制可能是NP导致脂肪细胞分化基因CEBP-α、SREBP-1、PPARγ表达异常有关。
[Abstract]:Objective to observe the effects of nonylphenol (NP) exposure on the weight of offspring, adipogenesis, adipocytes differentiation genes, liver and adipocytes in pregnant rats with high fat and high sugar content. To explore the mechanism of NP exposure to obesity in neonatal rats on the basis of high fat and high sugar diet during the parturient period. Methods 40 female and 20 male SD rats were selected and collected and randomly divided into common feed control group (OC group), high fat and high sugar diet control group (HC group), high fat and high sugar diet NP low dose group (HNL group). There were 10 rats in high dose group (HNH group) with high fat and high sugar diet (HNH group). OC group, HC group, HNL group and HNH group were fed with high fat and high sugar diet. From the 6th day of conception to the 21st day after delivery, the pregnant rats in OC group and HC group were given corn oil 0.5mL / (kg 路d), HNL group and HNH group were given NP 50100 mg/ (kg 路d), respectively. The offspring were breast-fed normally after birth and fed with common feed for 70 days after weanning. After 70 days of intervention, abdominal aortic blood was taken and serum TG,TC,HDL and LDL levels were measured by automatic biochemical analyzer. The body mass of the newborn rats was taken before the blood was taken, and the fat mass was measured by the parapadal fat pad after the blood was taken, and the fat coefficient was calculated. The expression of transcriptional regulatory factor (CEBP- 伪), sterol regulated binding protein (SREBP-1) and peroxisome proliferator activated receptor gamma (PPAR 纬) mRNA, which regulate adipocytes differentiation, were detected by Real Time PCR assay. The morphology of liver cells and adipocytes was observed by HE staining. Results the serum TG,TC,LDL in HNL group and HNH group was higher than that in HC group (P < 0.01). HNL group). The body mass and fat coefficient of HNH group were higher than those of HC group. The fat quality of HNH group was higher than that of HC group (P < 0.01). The expression of CEBP- 伪 mRNA in CEBP- 伪 mRNA group was higher than that in OC group (P < 0.01). The expression of SREBP-1, PAPAR 纬 mRNA in). HNH group was higher than that in HC group (P < 0.01). HE staining). Some steatosis of liver cells could be seen in HC group, a large number of fatty degeneration of hepatocytes could be seen in HNL group, and extensive balloon degeneration and a large number of lipid droplets could be seen in HNL group. The area of some adipocytes increased in HC group and most adipocytes in HNL group. Conclusion combined exposure to NP can increase the body mass, fat mass and blood lipid content of neonatal rats, and lead to the increase of liver fat and adipocytes. The mechanism may be that NP leads to adipocytes differentiation genes CEBP- 伪, SREBP-1,. The abnormal expression of PPAR 纬 was related.
【作者单位】：遵义医学院公共卫生学院;遵义医学院附属医院;
【基金】：国家自然科学基金资助项目(81360439) 贵州省教育厅青年基金(黔教合KY字[2013]198) 贵州省科技厅遵义医学院联合基金重点项目(黔科合LH[2014]7543) 遵义医学院2015年重点学科建设经费资助项目
【分类号】：R714.7

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