黑线仓鼠PPARβ的部分序列的克隆及SNP分析
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摘要
黑线仓鼠(Cricetulus barabensis)繁殖力强,分布范围广,破坏性大,是我国北方农田的主要害鼠之一。通过研究影响其繁殖力的PPARβ基因(Peroxisomeproliferator-activated receptors β),从分子水平上揭示害鼠种群数量的波动机制,可为对鼠害的综合防控提供新的思路和方法。
     PPARβ基因作为核受体超家族成员之一,早在胚胎发育的早期阶段就已出现,与动物胚胎着床、胎盘的形成、胚胎发育、卵巢功能的维持等有着密切的关系。此外,在个体生长过程中,PPARβ分布广,对个体正常的生长发育有着重要的调节作用。本研究首次采用基因克隆的方法分离黑线仓鼠PPARβ部分序列,同时对黑线仓鼠种群内部分序列进行了单核苷酸多态性(SNP)分析,为黑线仓鼠种群暴发机制的研究从分子水平上提供理论依据。
     本研究以捕获于山东省的黑线仓鼠为研究对象,用RT-PCR方法克隆PPARβ mRNA外显子4-7的部分序列480bp(GenBank登录号:JN662960),并对其核苷酸和氨基酸序列、二级结构、空间结构进行了生物学分析和预测。在其结构分析过程中发现了特殊的结构区域:锌指结构。在蛋白质二级结构中Alpha螺旋占很大比例,但锌指结构则位于较小的疏水性区域中。将得到的黑线仓鼠PPARβ mRNA序列与其他物种PPARβ中相对应的mRNA序列进行同源性比对,并利用不同的方法构建了系统进化树,结果显示黑线仓鼠与啮齿目的金仓鼠(Mesocricetus auratus)、大鼠(Rattus norvegicus)、小鼠(Mus musculus)亲缘关系最近,与野猪(Sus scrof)、牛(Bos Taurus)、兔(Oryctolagus cuniculus)等哺乳动物亲缘关系较远,与人亲缘关系最远,这一结果与以上物种之间的传统分类进化关系相一致,说明PPARβ在进化上相对比较保守。
     本研究还首次用PCR法克隆并检测了山东地区30个黑线仓鼠的PPARβ基因部分序列(297bp)的多态性,该序列包括外显子6(175bp),内含子6(104bp)和外显子7(18bp)。利用DnaSPv5.0软件分析发现,该区段共有11种单倍型,10个多态位点,其中外显子6中有6个,内含子中有4个。分析该区段发现,转换有9个,颠换1个。PPARβ基因外显子区域碱基发生突变的概率较大,引起编码的相应的氨基酸发生改变。这与从人上研究该区域的结果相一致,也许与其功能有着密切的关系。丰富的单核苷酸多态性为种群遗传多样性提供了可能性,进而使物种能够更好的适应外界环境。
     本研究对黑线仓鼠繁殖相关基因——PPARβ进行了分子生物学方面的研究,研究结果将为从分子生物学角度寻找控制黑线仓鼠数量及其危害性的有效方法提供借鉴。
Cricetulus barabensis,wide distribution, the destructive wait for a reason, be in the north ofthe advantage of the farmland against one of the rat. Begin with breeding genes, from molecularlevel reveals harmful rat population fluctuation mechanism, provide new ideas forcomprehensive prevention and control the rat. This paper is mainly on the reproducive genePPARβ for the molecular biology study.
     PPARβ gene (Peroxisome proliferator-activated receptors beta) as one of the nuclearreceptor superfamily members, already appeared as early as in an early stage in embryonicdevelopment, and has close relationship with animal embryo implantation, the formation of theplacenta, the embryonic development, the maintenance of ovarian function, in addition inindividual growth process, PPAR β distribution is quite widespread and has important regulatoryrole to the normal growth and development of the individual. This is the first time amplify thePPAR β gene sequence of C.barabensis by cloning method, and made single-nucleotidepolymorphisms (SNPS) analysis in part sequence of C. barabensis, to provide the theory basis atthe molecular level for the C. barabensis.
     This study to capture in shandong province C. barabensis as the research object, withRT-polymerase chain reaction (PCR) cloning get PPAR β mRNA exon4-6part of the sequence480bp (GenBank registration number: JN662960), and make the biology analysis and forecastthe nucleotide, amino acid sequence, secondary structure and space structure. In its structureanalysis process found the special structure area: zinc finger structure. In the secondary structureof protein Alpha helix of accounting for a large scale, but zinc finger structure is located in thesmaller hydrophobic areas. To make the homology compared the corresponding PPAR β mRNAsequence of C. barabensis with Mesocricetus auratus, Mus musculus, Rattus norvegicus, Susscrof, Bos Taurus, Oryctolagus cuniculus,et al. and make the system evolutionary tree bydifferent methods. Results show that the C. barabensis has closest genetic relationship withMesocricetus auratus, Mus musculus, Rattus norvegicus, and further with Sus scrof, Bos Taurus,Oryctolagus cuniculus, and furthest with Homo sapiensc, this result with more species oftraditional classification relationship between evolution is consistent, explain PPAR beta can beevolutionary relatively conservative.
     With the first time use PCR method get the PPAR β gene297bp of thirty C.barabensis inShandong province, including exon6(175bp), introns6(104bp) and exon7(18bp).UseDnaSPv5.0software analysis found that, in this section, the number of Haplotypes:11; Variable(polymorphic) sites:10, among them, there are6in the exon6, and4in the intron. This sectionanalysis found that conversion has9; Transversion is1. PPAR β gene exon area the probability of mutations bases is larger, the cause of the amino acids encoding corresponding change. PPARβ gene rich SNP offers possibility for population genetic diversity and species can better adapt tothe external environment.
引文
[1]肖治术,张知彬,王玉山.啮齿动物鉴别虫蛀种子的能力及其对坚果植物更新的潜在影响[J].兽类学报,2003,23(4):312~320.
    [2]董京平,张知彬.鼠害的防治及鼠类对森林更新的研究进展[J].生物学通报,2008,43(1):10~12.
    [3]崔琳霞.运城地区农田鼠害的发生与防治.山西农业科学[J].2008,36(2):40~41.
    [4]姚圣忠,胡德夫,周娜陶,炜煜,宋淑霞,刘恋.我国森林啮齿动物的发生及防控措施研究现状[J].中国森林病虫,2005,24(5):22~26.
    [5]汪诚信.我国鼠害及其防治对策[J].中国媒介生物学及控制杂志,1996,7(1):62~65.
    [6]罗泽珣,陈卫,高武.中国动物志兽纲第6卷啮齿目下册仓鼠科[M].北京:科学出版社,2000,28~38.
    [7]纪树立.鼠疫[M].北京:人民卫生出版社,1988,156.
    [8]郑智民,姜志宽,陈安国.啮齿动物学[M].上海:上海交通大学出版社,2008,168~169.
    [9]张知彬.我国草原鼠害的严重性及防治对策[J].中国科学院院刊,2003(5):343~347.
    [10]穆成旺,任维新.黑线仓鼠的生物学特性及防治研究[J].甘肃农业科技,1999,(1):39.
    [11]汪泳庆,张知彬.大仓鼠种群遗传多样性的季节性变化[J].动物学报,2002,48(6):733~740.
    [12]吕国强,孟光,蒋化民.黑线仓鼠发生与防治研究初报[J].植物保护,1991,17(4):37~38.
    [13]王淑卿,杨荷芳,都守身,张知彬.黑线仓鼠的食物与食量[J].动物学报.1992,38(2):155-164.
    [14]沈建忠,吴光华.鼠的防治(三)—常见鼠种的形态与习性[J].中华卫生杀虫药械.2005,11(4):271-275.
    [15]杨玉平,周延林,张鹏利,侯希贤,董维惠.黑线仓鼠的生长发育的研究[J].兽类学报,1996,16(4):309~311.
    [16]侯希贤,张鸥利,杨玉平,董维惠.黑线仓鼠的食物和食量[J].中国鼠类防制杂志.1989,5(3):155-158.
    [17]张洁.北京大兴地区黑线仓鼠种群繁殖生态研究[J].兽类学报,1986,6(1):45~56.
    [18]鲍伟东,王德华,王祖望,周延林,王利民.内蒙古库布齐沙地和呼和浩特平原黑线仓鼠种群繁殖特征的比较[J].动物学杂志,2001,14(3):15~18.
    [19]李瑶,孙儒泳,王汶成,贾西西.长爪沙鼠和黑线仓鼠的温度选择比较[J].兽类学报,1988,8(1):55~59.
    [20]周延林,侯希贤,董维惠,杨玉平.黑线仓鼠肥满度的研究[J].兽类学报,1992,12(3):207~212.
    [21]张洁.北京地区黑线仓鼠年龄鉴定及种群年龄组成的研究[J].兽类学报.1985,5(2):141-150.
    [22]卢浩泉,李玉春,张学栋.黑线仓鼠种群年龄组成及其数量季节消长的研究[J].兽类学报,1987,7(1):28~34.
    [23]武文华,付和平,武晓东,杨玉平,董维惠,徐胜利.应用马尔可夫链模型预测长爪沙鼠和黑线仓鼠种群数量[J].动物学杂志,2007,42(6):69~78.
    [24]柳劲松,王德华,孙儒泳.东北地区黑线仓鼠的代谢产热特征及其体温调节[J].动物学报,2003,49(4):451~457.
    [25]王俊森,范琳琳,李云芳,张安民,徐德,黄绍斌.黑线仓鼠的染色体组型研究[J].解剖遗传,1996,2:27~30.
    [26]徐承水.曲阜孔林不同月份黑线仓鼠睾丸组织变化的比较研究[J].东北林业大学报,2000,28(5):137~138.
    [27]吴瑾.大仓鼠,黑线仓鼠,黑线姬鼠及社鼠线粒体DNA控制区全序列SNP分析[D].曲阜师范大学硕士学位论文,2006.
    [28]靳鹏.不同地理种群黑线仓鼠FSHβ部分序列克隆与SNP分析[D].曲阜师范大学硕士学位论文,2010.
    [29]王洪伟.黑线仓鼠MTNR1A的克隆及种群间的遗传多态性分析[D].曲阜师范大学硕士学位论文,2010.
    [30]刘璐.黑线仓鼠OB基因部分序列的克隆与SNP分析[D].曲阜师范大学硕士学位论文,2010.
    [31]赵文捷.黑线仓鼠OPN部分序列的克隆及其表达差异研究[D].曲阜师范大学硕士学位论文,2010.
    [32] Issemann I,Green S. Activation of a memerber of the steroid homone receptor superfamilyby peroxisome proliferators[J]. Nature,1990,347:645-649.
    [33] Dreyer C, Krey G, Keller H, Givel F, Helftenbein G and Wahli W. Control of theperoxisomal β-oxidation pathway by a novel family of nuclear hormone receptors[J]. Cell,1992,68:879–887.
    [34] Gottlicher M, Widmark E, Li Q and Gustafsson JA. Fatty acids activate a chimera of theclofibric acid-activated receptor and the glucocorticoid receptor [J]. Proceedings of the NationalAcademy of Sciences. USA,1992,89:4653–4657.
    [35] Sher T, Yi HF, McBride OW and Gonzalez FJ. cDNA cloning, chromosomal mapping, andfunctional characterization of the human peroxisome proliferator activated receptor [J].Biochemistry,1993,32(21):5598–5604.
    [36] A unified nomenclature system for the nuclear receptor superfamily[J].Cell,1999,97:161–163.
    [37] Kliewer SA,Forman BM, Blumberg B, Ong ES, Borgmeyer U, Mangelsdorf D J, UmesonoK,Evan RM. Differential expression and activation of a family of murine PPARs [J].Proceedings of the National Academy of Sciences,1994,91(15):7355-7359.
    [38] Plutzky J. PPARs as Therapeutic Targets: reverse cardiology?[J]. Science,2003,302(5644):406-407.
    [39] Grimaldi PA. Roles of PPARδ in the control of muscle development and metabolism[J].Biochemical Society Transactions,2003,31:1130-1132.
    [40]Peters JM, Lee SST, Li W, Ward JM, Gavrilova O, Everett C, Reitman ML, Hudson LD andGonzalez FJ. Growth, adipose, brain, and skin alterations resulting from targeted disruption ofthe mouse peroxisome proliferators activated receptor β[J]. Molecular and Cell Biology,2000,20(14):5119-5128.
    [41] Elbrecht A, Chen Y, Cullinan CA, Hayes N, Leibowitz M, Moller D E, Berger J. Molecularcloning, expression and characterization of human peroxisome proliferators activated receptorsgamma1and gamma2[J]. Biochemical and Biophysical Research Communications,1996,224(2):431-437.
    [42]孟和,李辉,王宇祥.鸡PPARs基因组织表达特性的研究[J].遗传学报,2004,31(7):682-687.
    [43] Mandrup S, Lane MD. Regulating adipogenesis[J]. Journal of Biological Chemistry,1997,272(9):5367-5370.
    [44] Nanji AA, Dannenberg AJ, Jokelainen K and Bass N M. Alcoolic liver injury in the rat isassociated with reduced expression of Perosisome proliferators-α(PPARα) regulated genes andis ameliorated by PPARα activation[J].Journal of Pharmacology and Experimental Therapeutics,2004,310(1):417-424.
    [45] Ip E, Farrel G, Hall P, Robertson G,Leclercq I. Administration of the potent PPAR α agonist,Wy-14643, reverses nutritional fibrosis and steatohepatitis in mice[J]. Hepatology,2004,39(5):1286-1296.
    [46] Rusyn I, Rose M L, Bojes H K and Thurman R G.Novel role of oxidants in the molecularmechanism of action of peroxisome proliferators[J].Antioxidants Redox Signaling,2000,2(3):607-611.
    [47] Pascual G, Fong A L, Ogawa S, Gamliel A, Li A C, Perissi V, Rose D W, Willson T M,Rosenfeld M G and Glass C K. A sumoylation-dependent pathway mediates transrepression ofinflammatory response genes by PPARγ[J]. Nature,2005,437:759-763.
    [48] Ray D M, Akbiyik F, Phipps R P. The peroxisome proliferator-activated receptor γ (PPAR γ)ligands15-deoxy-12,14-prostaglandin J2and ciglitazone induce human B lymphocyte and B celllymphoma apoptosis by PPARγ-independent mechanisms [J]. Journal of Immunology,2006,177(8):5068-5076.
    [49] Kim E J, Kwon K J, Park J Y, Lee S H, Moon C H and Baik E J. Effects of peroxisomeproliferator-activated receptor agonists on Lps-induced neuronal death in mixed cortical neurons:associated with iNOS and COX2[J]. Brain Research,2002,941(1-2):1-10.
    [50] Naito Y, Yoshikawa T. Thiazolidinediones: a new class of drugs for the therapy ofischemia-reperfusion injury [J]. Drugs Today,2004,40(5):423.
    [51] Mao Qiang M, Fowler A J, Schmuth M, Lau P, Chang S, Brown BE, Moser AH, Michalik L,Desvergne B, Wahli W, Li M, Metzger D, Chambon PH, Elias PM, Feingold KR. Peroxisomeproliferator-activated receptor (PPAR)-γ activation stimulates keratinocyte differentiation [J].Invest Dermztol,2004,123(2):305-312.
    [52]郑可. PPARγ及其配体与类风湿关节炎的研究进展[J].海南军医,2011,22(16):110-113.
    [53]Beauregard C, Brandt P C.Peroxisome proliferator activated receptor inhibiterleukin-1β-mediated nitric oxide production in cultured lacrimal gland acinar cells [J]. Journal ofOcular Pharmacology and Therapeutics,2003,19(6):579-587.
    [54]Malapaka RR, Khoo S, Zhang J, Choi JH, Zhou XE, Xu Y, Gong Y, Li J, Yong EL, ChalmersMJ, Chang L, Resau JH, Griffin PR, Chen YE, Xu HE. Identification and Mechanism of10-Carbon Fatty Acid as Modulating Ligand of Peroxisome Proliferator-activated Receptors[J].Journal of Biolchemistry,2012,287,183-195.
    [55]燕晓阳,黄群策,王刘强.中国北方汉族人群PPARδ基因C/T多态研究[J].郑州大学学报,2011,42(3):118-120.
    [56]田亚东,亢娟娟,孙桂荣,韩瑞丽,康相涛. PPARα基因对安卡×固始鸡资源群胴体品质的遗传效应分析[J].华北农学报,2010,25(6):14-16.
    [57]樊月圆,昝林森,王洪宝,付常振.牛过氧化物酶体增殖激活受体α(PPARα)基因第5外显子多态性与胴体、肉质性状的相关性[J].农业生物科技学报,2010,18(4):713-718.
    [58] Schmidt A, Endo N, Rutledge S J, Vogel R, Shinar D and Rodan G A. Identification of a newmember of the steroid hormone receptor superfamily that is activated by a peroxisome proliferatorand fatty acids[J]. Molecular Endocrinology,1992,6(10):1634-1641.
    [59] Jones P S, Savory R, Barratt P. Chromosomal localization, inducibility, tissue-specificexpression and strain differences in three murine peroxisome proliferator activated receptorgenes [J]. European Journal of Biochemistry.1995,233(1):219~226.
    [60] Larsen L K, Amri E-Z, Mandrup S, Pacot C and Kristiansen K. Genomic organization of themouse peroxisome proliferator activated receptor β gene: alternative promoter usage and splicingyield transcripts exhibiting differential translational efficiency[J].Biochemical Journal.2002,366(3),767-775.
    [61] Hihi A K, Michalik L, Wahli W. PPARs:transcriptional effectors of fatty acids and theirderivatives[J]. Cellular and Molecular Life Sciences.2002;59:790-798.
    [62] Kice-Wilk B, Dembinska A, Olszanecka A, Bodzioch M and Kawecka K. The selectedpathophysiological aspects of PPARs activation[J]. Journal of Physiology and Pharmacology,2005,56(2):149-162.
    [63] Escher P, Braissant O, Basu-Modak S, Michalik L,Wahli W, Desvergne B. Rat PPARs:quantitative analysis in adult rat tissues and regulation in fasting and refeeding[J]. Endocrinology,2001,142(10):4195-4202.
    [64] Higashiyama H, Billin A N, Okamoto Y, Kinoshita M and Asano S. Expression profiling ofperoxisome proliferator-activated receptor-delta (PPAR-delta) in mouse tissues using tissuemicroarray[J]. Histochemistry and Cell Biology,2007,127(5):485-494.
    [65] Lim H, Gupta RA, Ma WG, Paria BC, Moller DE, Morrow JD,DuBais RN, TrzaskosJm,Dey SK. Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in themouse via PPARdelta[J]. Genes Development,1999,13(12):1561-1574.
    [66] Wendling O, Chambon P and Mark M. Retinoid X receptors are essential for early mousedevelopment and placentogenesis[J]. Proceedings of the National Academy Sciences. USA,1999,96(2):547-551.
    [67] Barak Y, Liao D, He W. Ong ES, Nelson MC, Olefsky JM,Boland R, Evans RM. Effects ofperoxisome proliferator-activated receptor β on placentation, adiposity and colorectal cancer[J].Proceedings of the National Academy Sciences. USA,2002,99:303~308.
    [68] Braissant O, Wahli W. Differential expression of peroxisome proliferator-activatedreceptor-α,-β and-γ during rat embryonic development[J].Endocrinology,1998,139(6):2748~2754.
    [69] Komar CM, Curry TE Jr. Localization and expression of messenger RNAs for theperoxisome proliferator-activated receptors in ovarian tissue from naturally cycling andpseudopregnant rats[J]. Biology of Reproduction,2002,66(5):1531–1539.
    [70]Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM. Proxisomeproliferator-activated receptor δ activates fat metabolism to prevent obesity[J].Cell,2003,113:159-170.
    [71] Luquet S, Lopez-soriano J, Holst D, Fredenrich A, Melki J, Rassoulzadegan M, Grimaldi PA.Peroxisome proliferator-activated receptor δ contorls muscle development and oxidativecapability[J]. FASEBJ,2003,17:2299-2301.
    [72]Shaw N, Elholm M, Noy N. Retinoic Acid Is a High Affinity Selective Ligand for thePeroxisome Proliferator-activated Receptor β/δ[J]. Journal of Biological Chemistry,2003,278(43):41589-41592.
    [73]Chawla A, Lee C-H, Barak Y, He W, Rosenfeld J, Liao D, Han J, Kang H and Evan RM.PPARδ is a very low-density lipoprotein sensor in macrophages[J].Proceedings of the NationalAcademy Sciences,2003,100(3):1268-1273.
    [74] Broooks CDW, Summers JB. Modulators of leukotriene biosynthesis and receptoractivation[J]. Journal of Medicinal Chemistry,1996,39:2629–2654.
    [75] Sznaidman ML, Haffner CD, Maloney PR. Novel Selective Small molecule agonists forperoxisome proliferator-activated receptor δ (PPARδ)-Synthesis and biological activity [J].Bioorganic and Medicainal Chemistry Letters,2003,13(9):1517-1521.
    [76] Xu C, Wang LI, Cao YL and Li S. PPARs: Target for lipid metabolism disorder and insulinresistance therapy[J]. Chinese Pharmacol Bull,2004,20(3):24l-244.
    [77] Grimaldi PA. Regulatory role of peroxisome proliferators-activated receptor delta (PPARδ)in muscle metabolism. A new target for metabolic syndrome treatment?[J]. Biochimie,2005,87(1):5-8.
    [78] Gilde AJ, vander LKA, Willemsen PHM, Chinetti G. Peroxisome proliferator-activatedreceptor (PPAR) α and PPARβ/δ, but not PPARγ, modulate the expression of genes involved incardiac lipid metabolism[J]. Circulation Research,2003,92:518-524
    [79]vander Veen J N, Kruit J K, Havinga R. Reduced cholesterol absorption upon PPARδactivation coincides with decreased intestinal expression of NPC1L1[J]. Journal of lipid research,2005,46(3):526-534.
    [80]Sprecher DL, Massien C, Pearce G, Billin AN, Perlstein I, Willson TM, Hassall DG,Ancellin N, Patterson SD, Lobe DC, Johnson TG. Triglyceride:High-density lipoproteincholesterol effects in healthy subjects administered a peroxisome proliferator activated receptor δagonist[J]. Arteriosclerosis, thrombosis,and Vascular Biology,2007;27:359-365.
    [81]Kramer D K, Al-Khalili L, Guigas B,Leng Y,Carcia-Roves PM,Krook Anna. Role of AMPkinase and PPARδ in the regulation of lipid and glucose metabolism in human skeletal muscle[J].Journal of Biological Chemistry,2007,282(27):19313-19320.
    [82]Lee C-H, Chawla A, Urbiztondo N,Liao D,Biosvert W A, Evans R M. Transcriptionalrepression of atherogenic inflammation: modulation by PPARδ[J]. Science,2003,302(5644):453-457.
    [83]Takata Y, Liu J, Yin F, Collins A R. PPARδ-mediated antiinflammatory mechanisms inhibitangiotensin II-accelerated atherosclerosis[J]. Science,2008,105(11):4277-4282.
    [84]Wang D, Wang H, Guo Y, Ning W, Katkuri S, Wahli W, Desvergne B, Dey S K, DuBois RN. Crosstalk between peroxisome proliferator-activated receptor δ and VEGF stimulates cancerprogression[J]. Proceedings of the National Academy Sciences. USA,2006,103(50):19069-19074.
    [85]葛颂,洪德元.遗传多样性及其检测方法[A].见:钱迎倩,马克平主编.生物多样性研究的原理与方法[C].北京:中国科学技术出版社,1994,122~140.
    [86]季维智,宿兵.遗传多样性研究的原理与方法[C].杭州:浙江科学出版社,1999.
    [87]Vignal A, Milan D, SanCristobal M, Eggen A. A review on SNP and other types of molecularmarkers and their use in animal genetics[J]. Genetics Selection Evolution,2002,34:275~305.
    [88] Authony B. SNP attack on complex traits[J]. Nature Genetics,1998,20(3):217~218.
    [89] Magge S S, Guardiola-Diaz H M. Characterization of the mouse peroxisome proliferatoractivated receptor β gene[J]. Biochemical Biophysical Research Communications,2002,290(1):230-235.
    [90] Sans M D, Tashiro M, Vogel N L,Kimball SR, D'Alecy LG, Williams JA. Leucine activatespancreatic translational machinery in rats and mice through mTOR independently of CCK andinsulin[J]. The Journal of nutrition,2006,136(7):1792-1799.
    [91]毛湘冰.亮氨酸与瘦素协同调节生长鼠骨骼肌蛋白质代谢的研究[D].博士学位论文,北京:中国农业大学,2010.
    [92]Um S H, Frigerio F, Watanabe M. Absence of S6K1protects against age-and diet-inducedobesity while enhancing insulin sensitivity[J]. Nature,2004,431(7005):200-205.
    [93] Düvel K, Yecies J L, Menon S. Activation of a metabolic gene regulatory networkdownstream of mTOR complex1[J]. Molecular Cell,2010,39(2):171-183.
    [94] Oliver WR Jr, Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, Lewis MC,Winegar DA, Sznaidman ML, Lambert MH, Xu HE, Sternbach DD, Kliewer SA, Hansen BC,Willson TM. A selective peroxisome proliferators-activated receptor δ agonist promotes reversecholesterol transport[J]. Proceedings of the National Academy Sciences. USA,2001,98(9):5306-5311.
    [95]Brunmair B, Staniek K, Dorig J. Activation of PPAR-β in isolated rat skeletal muscleswitches fuel preference from glucose to fatty acids[J]. Diabetologia,2006;49(11):2713-2722.
    [96] Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM. Peroxisomeproliferator-activated receptor δ activates fat metabolism to prevent obesity[J]. Cell,2003,113(2):159-170.
    [97] Robins DM. Androgen receptor and molecular mechanisms of male-specific geneexpression[J]. Novartis Foundation Symposium,2005,268:42-52.
    [98] Maor S, Mayer D, Yarden R I, Lee AV, Sarfstein R, Werner H, Papa MZ. Estrogen receptorregulates insulin-like growth factor-1receptor gene expression in breast tumor cells:involvement of transcription factor Sp1[J]. Journal of Endocrinology,2006,191(3):605-612.
    [99] Klug A. Zinc finger peptides for the regulation of gene expression [J]. Journal of BiologicalChemistry,1999,293(2):215-218.
    [100]赵楠,赵飞,李玉花.锌指蛋白结构及功能研究进展[J].生物技术通讯,2009,20(1):131-134.
    [101]马瑶,程东海.PPAR基因多态性的研究[J].中国优生与遗传杂志.2007,15(9):6~9.
    [102] Clements J R, Magnusson K R, Beitz A J. Ultrastructural description of glutamate-,aspartate-,taurine-, and glycine-like immunoreative terminals from five rat brain reaions. Journalof Electron Microscopy Technique,1990;15:49~66.
    [103] Bereiter D A,Bereiter D F. NMDA and non-NMDA receptor antagonism reduces Fos-likeimmunoreactivity in central trigeminal neurona after corneal stimulation in the rat.Neuroscience,1996;73:249~257.
    [104] Song Y, Huang L Y M.Modulation of glycine receptor chloride channels bycamp-dependent protein kinase in spinal trigeminal neurons. Nature,1990,73:249~257.
    [105]庄瑞春,杨俊卿. PPARβ在中枢神经系统中的作用研究进展[J].生命科学.2008,20(1):101~104.
    [106] Basu-Modak S, Braissant O, Escher P, Desvergne B, Honegger P and Wahli W.Peroxisome proliferator-activated receptor β regulates acyl-CoA synthetase2in reaggregated ratbrain cell cultures[J]. Journal of Biological Chemistry,1999,274(50):35881-35888.
    [107]杨金权,胡雪莲,唐文乔,林弘都.长江口邻近水域刀鲚的线粒体控制区序列变异与遗传多样性[J].动物学杂志,2008,43(1):8~15.
    [108]陈灵芝.中国的生物多样性[M].北京:上海科技出版社,99~113.

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