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圍產(chǎn)期高脂高糖孕鼠NP暴露對仔鼠肥胖的影響及機(jī)制探討

發(fā)布時(shí)間:2019-06-06 05:40
【摘要】:目的觀察圍產(chǎn)期高脂高糖孕鼠壬基酚(NP)暴露對子代體質(zhì)量、脂肪生成及脂肪細(xì)胞分化基因、肝臟和脂肪細(xì)胞變化的影響,探討在圍產(chǎn)期高脂高糖飲食基礎(chǔ)上NP暴露對仔鼠肥胖的作用機(jī)制。方法選擇SD大鼠雌性40只、雄性20只合籠交配,收集交配成功的孕鼠,隨機(jī)分為普通飼料對照組(OC組)、高脂高糖飼料對照組(HC組)、高脂高糖飼料+NP低劑量組(HNL組)、高脂高糖飼料+NP高劑量組(HNH組)各10只。普料OC組食用普通飼料,HC組、HNL組、HNH組均食用高脂高糖飼料。從母鼠受孕第6天到產(chǎn)后第21天,OC組、HC組孕鼠均予玉米油0.5 m L/(kg·d)灌胃,HNL組、HNH組分別予NP 50、100 mg/(kg·d)灌胃。仔鼠出生后正常進(jìn)行母乳喂養(yǎng),斷乳后均以普通飼料喂養(yǎng)至70 d。干預(yù)70 d后,取仔鼠腹主動脈血,采用全自動生化分析儀檢測血清TG、TC、HDL及LDL水平。取血前稱仔鼠體質(zhì)量,取血后取性腺旁脂肪墊測脂肪質(zhì)量,計(jì)算脂肪系數(shù)。取仔鼠肝臟組織,采用Real Time PCR法檢測調(diào)控脂肪細(xì)胞分化的關(guān)鍵基因轉(zhuǎn)錄調(diào)節(jié)因子(CEBP-α)、固醇調(diào)節(jié)結(jié)合蛋白(SREBP-1)、過氧化物酶體增殖物激活受體γ(PPARγ)mRNA的表達(dá)。取仔鼠肝臟組織和性腺旁脂肪組織,采用HE染色法觀察肝臟細(xì)胞和脂肪細(xì)胞形態(tài)。結(jié)果 HNL組、HNH組血清TG、TC、LDL均高于HC組(P均0.01)。HNL組、HNH組體質(zhì)量、脂肪系數(shù)均高于HC組,HNH組脂肪質(zhì)量高于HC組(P均0.01)。HNH組CEBP-αmRNA表達(dá)高于OC組(P0.01)。HNH組的SREBP-1、PPARγmRNA表達(dá)均高于HC組(P均0.01)。HE染色示,HC組可見部分肝臟細(xì)胞脂肪變性,HNL組可見大量肝細(xì)胞脂肪樣變,HNL組可見肝細(xì)胞廣泛氣球樣變和大量脂滴;HC組部分脂肪細(xì)胞面積增大,HNL組大部分脂肪細(xì)胞面積明顯增大。結(jié)論圍產(chǎn)期高脂高糖孕鼠NP聯(lián)合暴露可增加仔鼠體質(zhì)量、脂肪質(zhì)量、血脂含量,導(dǎo)致肝臟脂肪樣和脂肪細(xì)胞增大增多,其機(jī)制可能是NP導(dǎo)致脂肪細(xì)胞分化基因CEBP-α、SREBP-1、PPARγ表達(dá)異常有關(guān)。
[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- 偽), sterol regulated binding protein (SREBP-1) and peroxisome proliferator activated receptor gamma (PPAR 緯) 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- 偽 mRNA in CEBP- 偽 mRNA group was higher than that in OC group (P < 0.01). The expression of SREBP-1, PAPAR 緯 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- 偽, SREBP-1,. The abnormal expression of PPAR 緯 was related.
【作者單位】: 遵義醫(yī)學(xué)院公共衛(wèi)生學(xué)院;遵義醫(yī)學(xué)院附屬醫(yī)院;
【基金】:國家自然科學(xué)基金資助項(xiàng)目(81360439) 貴州省教育廳青年基金(黔教合KY字[2013]198) 貴州省科技廳遵義醫(yī)學(xué)院聯(lián)合基金重點(diǎn)項(xiàng)目(黔科合LH[2014]7543) 遵義醫(yī)學(xué)院2015年重點(diǎn)學(xué)科建設(shè)經(jīng)費(fèi)資助項(xiàng)目
【分類號】:R714.7

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本文編號:2494110


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