宫内发育迟缓新生大鼠胰腺中MafA的表达
- 王艳芳,刘颖,付大军,程士凯,成晓君,杜在永
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The expression of MafA in pancreas of newborn rats with intrauterine growth retardation.
- WANG Yan-fang,LIU Ying,FU Da-jun,CHENG Shi-kai,CHENG Xiao-jun,DU Zai-yong.
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摘要
目的 观察宫内发育迟缓(intrauterine growth restriction,IUGR)新生大鼠胰腺中MafA的表达。方法 清洁级Wister大鼠,雌雄鼠5∶1合笼,孕鼠按受孕顺序随机分为两组(低蛋白组和对照组),低蛋白组自妊娠第1天至分娩给予低蛋白饲料,对照组妊娠全程给予标准饲料。测量IUGR组和对照组新生大鼠空腹血糖及糖负荷后的血糖,摘取胰腺组织,称重,采用HE染色,光镜观察胰腺形态学变化,应用免疫组织化学法检测新生大鼠胰腺组织中MafA的表达。结果 IUGR组新生大鼠空腹血糖低于对照组,给予糖负荷后,IUGR组血糖下降较慢,至120 min仍明显高于对照组(P<0.05);胰重显著低于对照组(P<0.05)。与对照组相比,IUGR组胰腺表现为组织松散,胰岛数量及面积减少,胰腺中MafA的表达明显低于对照组(P<0.05)。 结论 宫内蛋白营养不良可致大鼠发生IUGR,IUGR新生大鼠胰腺中MafA的表达下降,这可能是影响新生大鼠胰腺发育和功能完善的机制之一。
Abstract
Objective To investigate the expression of MafA in pancreas of rats with intrauterine growth retardation(IUGR). Methods Female and male Wister rats were copulated by 5∶1,followed by randomly dividing into two groups:low protein group(LPG)and control group(CG).Rats in LPG were treated with low protein fodder from 1st day after pregnancy until delivery; meanwhile,standard fodder was given to the rats in CG.Fasting blood glucose and blood glucose after glucose load were detected between IUGR and CG.The removed pancreas of the rats measured weight.HE staining was applied to detect the pancreatic morphological changes under light microscope.Eventually,immunohistochemisty staining was performed to detect the expression of MafA in pancreas of rats. 【Result】 Statistically significant reduction of fasting blood glucose were observed in IUGR compared with CG.Likewise,the pancreatic weight was significantly depressed in IUGR compared with CG(P<0.05);however,slowly decrease of blood glucose in IUGR was observed after glucose load given,yet,it was still significantly higher in LPG until 120 min compared with CG.The most striking finding was that lower expression of MafA was detected in IUGR compared with CG(P<0.05). Conclusion LPG may cause IUGR of rats and the lower expression of MafA in pancreas of newborn rats.It may influences the development of generation and systems of the pancreas of newborn rats.
关键词
Key words
intrauterine growth restriction / rats / development of pancreas / MafA
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参考文献
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[11] Coolen M,Sii-Felice K,Bronchain O,et al.Phylogenomic analysis and expression pattern of large Maf genes in Xenopus tropicalis provide new insights into the functional evolution of the gene family in osteichthyans[J].Dev Genes Evol,2005,215(7):327-339.
[12] Matsuoka TA,Artner I,Henderson E,et al.The MafA transcription factor appears to be responsible for tissuespecific expression of insulin[J].Proc Natl Acad Sci USA,2004,101(9):2930-2933.
[13] Zhang C,Moriguchi T,Kajihara M,et al.MafA is a key regulator of glucose-stimulated insulin secretion[J].Mol cell Biol,2005,25(12):4969-4976.
[14] Wang H,Brun T,Kataoka K,et al.Mafa controls genes implicated in insulin biosynthesis and secretion[J].Diabetologia,2007,50(2):348-358.
[15] Matsuoka TA,Kaneto H,Stein R,et al.MafA regulates expression of genes important to islet beta-cell function[J].Mol Endocrinol,2007,21(11):2764-2774.
[2] Whincup PH,Kaye SJ,Owen CG.Birth weight and risk of type 2 diabetes:a systematic review[J].JAMA,2008,300(24):2886-2897.
[3] Tian JY,Cheng Q,Song XM,et al.Birth weight and risk of type 2 diabetes,abdominal obesity and hypertension among Chinese adults[J].European Journal of Endocrinology,2006,155(4):601-607.
[4] Artner I,Hang Y,Mazur M,et al.MafA and MafB regulate genes critical to beta-cells in a unique temporal manner[J].Diabetes,2010,59(10):2530-2539.
[5] Gupta M,Gupta R,Pareek A,et al.Low birth weight and insulin resistance in mid and late childhood[J].Indian Pediatr,2007,44(3):177-184.
[6] Kataoka K,Shioda S,Ando K,et al.Differentially expressed Maf family transcription factors,c-maf and MafA,activate glucagons and insulin gene expression in pancreatic islet alpha-and betacell[J].Mol Endocrionl,2004,32(1):9-20.
[7] Aramata S,Han SI,Kataoka K.Roles and regulation of transcription factor MafA in islet beta2 cells[J].Endocr,2007,54(5):6592-6666.
[8] 丘小汕,沈振宇,黄婷婷,等.早期营养干预对宫内生长迟缓大鼠瘦素、胰岛素敏感性的影响[J].中华内分泌代谢杂志,2004,20(2):161-164.
[9] Dumortier O,Blondeau B,Duvillié B,et al.Different mechanisms operating during different critical time-windows reduce rat fetal beta cell mass due to a maternal low-protein or low-energy diet[J].Diabetologia,2007,50(12):2495-2503.
[10] Barnett MP,Phillips AR,Harris PM,et al.Impaired insulin secretion in perfused pancreases isolated from offspring of female rats fed a low protein whey-based diet[J].Jop,2008,9(4):477-488.
[11] Coolen M,Sii-Felice K,Bronchain O,et al.Phylogenomic analysis and expression pattern of large Maf genes in Xenopus tropicalis provide new insights into the functional evolution of the gene family in osteichthyans[J].Dev Genes Evol,2005,215(7):327-339.
[12] Matsuoka TA,Artner I,Henderson E,et al.The MafA transcription factor appears to be responsible for tissuespecific expression of insulin[J].Proc Natl Acad Sci USA,2004,101(9):2930-2933.
[13] Zhang C,Moriguchi T,Kajihara M,et al.MafA is a key regulator of glucose-stimulated insulin secretion[J].Mol cell Biol,2005,25(12):4969-4976.
[14] Wang H,Brun T,Kataoka K,et al.Mafa controls genes implicated in insulin biosynthesis and secretion[J].Diabetologia,2007,50(2):348-358.
[15] Matsuoka TA,Kaneto H,Stein R,et al.MafA regulates expression of genes important to islet beta-cell function[J].Mol Endocrinol,2007,21(11):2764-2774.
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辽宁省教育厅资助(09730A)
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