宫内生长受限大鼠肝组织胰岛素样生长因子-2与过氧化物酶体增殖物激活受体-γ辅激活因子-1α表达的相关性
궁내생장수한대서간조직이도소양생장인자-2여과양화물매체증식물격활수체-γ보격활인자-1α표체적상관성
Relation between expression of insulin-like growth factor-2 and peroxisome proliferator-activated receptor-γ coactivator-1α in fetal growth restricted rats
  • 万方数据
    中华围产医学杂志 중화위산의학잡지
    CHINESE JOURNAL OF PERINATAL MEDICINE
    2013年 12期 759-765 ,共7页

    张美慧%廖立红%谢雪梅%周秀云%叶娟%应艳琴%宁琴%罗小平

    장미혜%료립홍%사설매%주수운%협연%응염금%저금%라소평

    胎儿生长迟缓%胰岛素样生长因子2%转录因子%RNA结合蛋白质类%代谢综合征X 胎兒生長遲緩%胰島素樣生長因子2%轉錄因子%RNA結閤蛋白質類%代謝綜閤徵X
    태인생장지완%이도소양생장인자2%전록인자%RNA결합단백질류%대사종합정X
    Fetal growth retardation%Insulin-like growth factor 2%Transcription factors%RNA-binding proteins%Metabolic syndrome X
    目的 探讨胎儿生长受限(fetal growth restriction,FGR)仔鼠生后追赶生长导致成年期代谢综合征的发生机制.方法 孕Sprague Dawley大鼠随机分为正常饮食组和限制饮食组,各10只.限制饮食组孕鼠摄食量为正常饮食组孕鼠摄食量的30％,建立FGR仔鼠模型.限制饮食组和正常饮食组孕鼠妊娠19d时,取胎盘和胎鼠肝组织.限制饮食组新生仔鼠体重低于正常饮食组仔鼠体重平均值2个标准差者定义为FGR仔鼠.取新生仔鼠、4及8周龄完成追赶生长的仔鼠的肝组织,采用实时荧光定量-聚合酶链反应及Western印迹技术检测胎盘及不同周龄仔鼠肝组织胰岛素样生长因子-2(insulin-like growth factor-2,IGF-2)、磷脂酰肌醇3-激酶(phosphatidylinositol 3 kinase,PI3-K)、蛋白激酶(serine/threonine protein kinases,AKT2)、磷酸化AKT2 (phosphorylation of AKT2,AKT2-P)和过氧化物酶体增殖物激活受体-γ辅激活因子-1α(peroxisome proliferator-activated receptor-γ coactivator 1α,PGC-1α)mRNA及蛋白表达水平.测定8周龄完成追赶生长的FGR仔鼠和对照组仔鼠血浆甘油三酯浓度,并取新鲜肝组织,HE染色和油红O染色观察肝组织病理改变.采用t检验和Pearson直线相关分析进行统计学分析.结果 FGR仔鼠胎盘、胎肝、新生肝、4周肝组织中IGF 2 mRNA的表达水平分别为0.665±0.210、7.855±0.354、6.714±0.744和(4.510±0.490)×10-4,均低于对照组[分别为1.608±0.464、9.548±0.416、13.053±1.415和(22.800±0.060)×101](t分别为4.535、7.175、9.713和4.580,P均＜0.01).FGR仔鼠胎盘、胎肝、新生肝组织中PI3-K、AKT2、AKT2 P和PGC-1α的蛋白表达水平均分别较对照组显著降低(P均＜0.01).8周龄仔鼠肝组织内IGF-2 mRNA表达检测不出,但PI3-K、AKT2、PGC hα mRNA的表达水平分别为0.380±0.150、1.020±0.019和0.280±0.160,均显著低于对照组(分别为1.510±0.220、2.360±0.360和0.680±0.350)(t分别为14.700、12.876和3.750,P均＜0.01);8周龄完成追赶生长的FGR仔鼠肝组织中PI3-K、AKT2、AKT2-P、PGC-1α蛋白的表达水平分别为0.660±0.044、1.110±0.120、0.360±0.087和0.170±0.071,均显著低于对照组(分别为0.900±0.046、1.970±0.200、0.740±0.064和0.470±0.110)(t分别为13.061、12.773、12.188和7.938,P均＜0.01).8周龄时,完成追赶生长的FGR仔鼠肝组织有轻度脂肪变性,血浆甘油三酯浓度为(0.321±0.110) mmol/L,明显高于对照组仔鼠[(0.189±0.038) mmol/L](t=3.790,P＜0.05).在FGR组,胎盘、胎肝和新生肝组织中PGC-1α蛋白与IGF-2 mRNA的表达量均呈正相关(r分别为0.991、0.935和0.873,P均＜0.05);8周龄完成追赶生长的FGR仔鼠肝组织PGC 1α蛋白与血浆甘油三酯的表达量呈负相关(y=-0.827,P＜0.05).结论 IGF-2可能通过PI3-K/AKT2通路调控FGR大鼠PGC-1α的表达,影响糖脂代谢,参与追赶生长大鼠成年后代谢综合征的发生.
    목적 탐토태인생장수한(fetal growth restriction,FGR)자서생후추간생장도치성년기대사종합정적발생궤제.방법 잉Sprague Dawley대서수궤분위정상음식조화한제음식조,각10지.한제음식조잉서섭식량위정상음식조잉서섭식량적30％,건립FGR자서모형.한제음식조화정상음식조잉서임신19d시,취태반화태서간조직.한제음식조신생자서체중저우정상음식조자서체중평균치2개표준차자정의위FGR자서.취신생자서、4급8주령완성추간생장적자서적간조직,채용실시형광정량-취합매련반응급Western인적기술검측태반급불동주령자서간조직이도소양생장인자-2(insulin-like growth factor-2,IGF-2)、린지선기순3-격매(phosphatidylinositol 3 kinase,PI3-K)、단백격매(serine/threonine protein kinases,AKT2)、린산화AKT2 (phosphorylation of AKT2,AKT2-P)화과양화물매체증식물격활수체-γ보격활인자-1α(peroxisome proliferator-activated receptor-γ coactivator 1α,PGC-1α)mRNA급단백표체수평.측정8주령완성추간생장적FGR자서화대조조자서혈장감유삼지농도,병취신선간조직,HE염색화유홍O염색관찰간조직병리개변.채용t검험화Pearson직선상관분석진행통계학분석.결과 FGR자서태반、태간、신생간、4주간조직중IGF 2 mRNA적표체수평분별위0.665±0.210、7.855±0.354、6.714±0.744화(4.510±0.490)×10-4,균저우대조조[분별위1.608±0.464、9.548±0.416、13.053±1.415화(22.800±0.060)×101](t분별위4.535、7.175、9.713화4.580,P균＜0.01).FGR자서태반、태간、신생간조직중PI3-K、AKT2、AKT2 P화PGC-1α적단백표체수평균분별교대조조현저강저(P균＜0.01).8주령자서간조직내IGF-2 mRNA표체검측불출,단PI3-K、AKT2、PGC hα mRNA적표체수평분별위0.380±0.150、1.020±0.019화0.280±0.160,균현저저우대조조(분별위1.510±0.220、2.360±0.360화0.680±0.350)(t분별위14.700、12.876화3.750,P균＜0.01);8주령완성추간생장적FGR자서간조직중PI3-K、AKT2、AKT2-P、PGC-1α단백적표체수평분별위0.660±0.044、1.110±0.120、0.360±0.087화0.170±0.071,균현저저우대조조(분별위0.900±0.046、1.970±0.200、0.740±0.064화0.470±0.110)(t분별위13.061、12.773、12.188화7.938,P균＜0.01).8주령시,완성추간생장적FGR자서간조직유경도지방변성,혈장감유삼지농도위(0.321±0.110) mmol/L,명현고우대조조자서[(0.189±0.038) mmol/L](t=3.790,P＜0.05).재FGR조,태반、태간화신생간조직중PGC-1α단백여IGF-2 mRNA적표체량균정정상관(r분별위0.991、0.935화0.873,P균＜0.05);8주령완성추간생장적FGR자서간조직PGC 1α단백여혈장감유삼지적표체량정부상관(y=-0.827,P＜0.05).결론 IGF-2가능통과PI3-K/AKT2통로조공FGR대서PGC-1α적표체,영향당지대사,삼여추간생장대서성년후대사종합정적발생.
    Objective To explore the potential mechanism of metabolism syndrome formation in fetal growth restriction (FGR) rats with catch-up growth (CG-FGR).Methods Pregnant SpragueDawley rats were randomly divided into normal nutrition group and nutrition restriction group,10 rats in each.The food intake of nutrition restriction group was 30％ of that of normal nutrition group,so as to establish the FGR rat model.Three pregnant rats in each group were sacrificed at their 19th gestational day,the placentas and fetal livers were collected.The newborn rats in nutrition restriction group whose birth weights were two standard deviations lower than the mean birth weights of normal nutrition group were defined as FGR rats.The liver of newborn rats,4-week and 8-week CG-FGR rats were collected.Real-time polymerase chain reaction and Western blot were used to detect the mRNA and protein levels of insulin-like growth factor-2 (IGF-2),phosphatidylinositol 3-kinase (PI3-K),serine/threonine protein kinases-2 (AKT2),phosphorylation of AKT2 (AKT2-P) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in placenta and liver tissues.The plasma triglyceride levels of CG-FGR rats and normal rats at 8-week were detected,and their livers were stained by HE and Oil red O to observe the pathological changes.Pearson linear correlation analysis and t-test were applied for statistics.Results IGF-2 mRNA levels of FGR rats (as in placenta,fetal liver,newborn liver and 4-week rat liver) were lower than those of the control rats [0.665±0.210 vs 1.608± 0.464,t =4.535; 7.855 ± 0.354 vs 9.548 ± 0.416,t =7.175; 6.714 ± 0.744 vs 13.053±1.415,t=9.713; (4.510±0.490)×10-4 vs (22.800±0.060)×10 4,t=4.580;all P＜0.01].The protein expressions of PI3 K,AKT2,AKT2-P and PGC-1α of FGR rats in placentas,fetal livers and newborn livers were lower than those of control rats (P＜0.01,respectively).Although IGF2 mRNA levels in 8-week rats' liver were detected in neither groups,the mRNA levels of PI3 K,AKT2 and PGC 1α in 8-week CG-FGR rats' liver were significantly lower than those of control group (0.380±0.150 vs 1.510±0.220,t=14.700; 1.020±0.019 vs 2.360± 0.360,t=12.876; 0.280±0.160 vs 0.680±0.350,t=3.750; all P＜0.01).The protein levels of PI3 K,AKT2,AKT2-P and PGC-1α in 8-week old CG-FGR rats' liver were lower than those of the control group (0.660±0.044 vs 0.900±0.046,t=13.061; 1.110±0.120 vs 1.970±0.200,t=12.773; 0.360±0.087 vs 0.740±0.064,t=12.188; 0.170±0.071 vs 0.470±0.110,t=7.938,all P＜0.01).Plasma triglyceride levels of 8-week old CG-FGR rats were higher than those of the control group[(0.321±0.110) mmol/Lvs (0.189±0.038) mmol/L,t=3.790,P＜0.05].Mild liver fatty degeneration was seen in CG-FGR rats.The protein expression of PGC-1α was positive correlated to the expression of IGF-2 mRNA in placenta (r =0.991,P＜0.05),fetal liver (r =0.935,P＜ 0.05) and newborn liver (r=0.873,P＜0.05) of FGR rats.The protein expression of PGC-1α in 8-week old CG-FGR liver was negatively correlated to plasma triglyceride level (r=-0.827,P＜0.05).Conclusions IGF-2 might affect the metabolism of glucose and lipid resulting from regulating the expression of PGC-1α in FGR rats by PI3 K/AKT2 pathway,which might participate in the onset of metabolic syndrome when they grow up.
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