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1、210Acta Physiologica Sinica, April 25, 2004, 56(2): 210-218Received 2003-09-16 Accepted 2003-10-27This work was supported by the National Basic Research Priorities Programme of China (G2000056906) and the National Natural ScienceFoundation of China (30070872). We appreciate technical assistance from
2、 Professor Eugene Chen (Morehouse School of Medicine, USA).* These authors contributed equally to this work.Corresponding author. Tel: +86-10-82802306; Fax: +86-10-62017700; E-mail: *, *, , , , , , *, 100083: , : (suprarenal abdomi-nal aortic stenosis, SRS)(arterial-vein fistula, AVF)(jugular vein i
3、nfusion of norepinephrine, NEi), , cDNASRSNEi, AVF, NEi , , , , , 19, : ; ; ; ; ; : Q463Comparison of changes in left ventricular gene expression profiles from different cardiac hypertrophy models in ratsLI Ping*, LI Jin-Liang*, FENG Xin-Heng, LI Zhao-Ping, YIN Feng, YAN Jie, HOU Rong, HAN Qi-De,ZHA
4、NG You-Yi*Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiology, Ministry of Education ,Beijing 100083, ChinaAbstract: To get insights into the principles of gene expression changes during cardiac hypertrophy, three rat cardiac hypertrophy models
5、 were prepared, i.e., suprarenal abdominal aortic stenosis (SRS), arterial-vein fistula (AVF) and continuous jugular vein infusion ofnorepinephrine (NEi). The cardiac function and structure were analyzed by echocardiograph as well as histological examination. Total RNA of left ventricles was extract
6、ed and gene expression profiles were analyzed by cDNA microarray. SRS and NEi induced concentriccardiac hypertrophy and AVF induced eccentric hypertrophy in rats, among which NEi caused obvious cardiac fibrosis. The changes of gene expression profiles were compared comprehensively across different p
7、athologic cardiac hypertrophy models. While gene expressionprofiles of different cardiac hypertrophy models compared with pairs, parts of the genes involved were found overlapped, and mostly the gene expression changed in the same direction between two models, but some of them changed in the opposit
8、e directions. Expression levelsof 19 genes were found changed across all cardiac hypertrophy models, and genes relatively regulated in a specific model was also found when comparison of all the three models was carried out. Novel clues for further study might derive from the results mentioned above,
9、and some genes might be the marker genes of cardiac hypertrophy or the targets of therapy.Key words: pathophysiology; gene expression; microarray; heart; hypertrophy; rathttp:/211: ,G(Gi)1, , RasGq2, , , , , 1 1.1 Wistar, , 21.1.1 (l-Norepi- nephrine , NE)(jugular vein infu-sion of NorepinephrineNEi
10、 : 230250 g,(2001,Alzet, ) NE(Sigma)(0.2 mg/kg.h-1)3 d3NE100 g/ml VitC (Sigma)VitC(arterial-vein fistula, AVF) 4: 200230 g , , 18G, , (suprarenal abdominal aortic Stenosis,SRS): 6(140155 g), , (6.5, 0.65 mm), 51.1.2 , (AcusonSequoia C256 ), 8 MHz, 2 cm, M, , , 100 mm/s, 3, , ( )/, , , , HE1.2 Geneti
11、c ResearchcDNA(microarray)(, GF300), 5184 cDNA , 33%, (expressed sequence tags, ESTs)() TRIZOL RNAGenetic Research: 46 RNA, RNA 8 g, 300 U Super-script, 3.7 MBq 33P-dCTP (Amersham ) 2 g Oligo dT 3790 min30 l, 1First strand Buffer, 3.3mmol/L DTT, 1 mmol/L dNTP(dATP, dGTP, dTTP)QIAquikMicroarray0.5%SD
12、S510 min, , MicroHyb , Cot-1 DNAPoly dA,422 h, 4218 h, 2SSC, 1% SDS 50220 min, 0.5SSC,1% SDS 5515 min, Storage Phos-phor Screen, 48 hCyclone Storage Phos- phor Scanner (Packard), , Invitrogen1.3 Pathway3.0(Genetic Research), 75 %, (raw intensity)(normalizedintensity)212Acta Physiologica Sinica, Apri
13、l 25, 2004, 56(2): 210-218, 50%2867(ESTs), (Ratio)RNA microarray, 195%1.650.62, , ratio1.7, 0.58meanSEM, t, P0.052 2.1 2, (LVW)/(LVW/BW), (PWTd) , (LVIDd), (1)-1 , / , (1)(NE)0.2 mg/kgh-1 3 d, ,/, (1)HE, , ; NE, ()2.2 2.2.1 SRSAVFNE1SRSAVF432SRSNE38 5AVF NE3414 (2)2.2.2 , 191. Table 1. Changes of he
14、art parameters in different cardiac hypertrophy modelSRS NEi AVFSham TreatedShamTreatedShamTreatedBW (g) 19710 18413 25010 2483 2474 2405LVW(g)0.470.020.670.04*0.570.020.750.02*0.560.010.700.01* LVW/BW2.370.063.680.22*2.300.093.020.10*2.350.022.850.08*PWTd (mm)1.650.132.330.07*1.950.122.530.24*1.860
15、.057.730.13* LVIDd (mm)5.700.045.340.04*5.390.284.830.48*6.030.131.630.09*FS(%) 68.81.970.55.260.53.870.82.6*63.72.261.31.7SRS, suprarenal abdominal aortic stenosis; NEi, jugular vein infusion of norepinephrine; AVF, arterial-vein fistula. BW, body weight; LVW,left ventricular weight; PWTd , thickness of diastolic left ventricle; LVIDd , inner dimension of diastolic left ventricle; FS, fractional shortening; MAP, mean arterial pressure. Data are meanSEM , *P0.05 vs sham group, n=56.213: 2. Table 2. Genes regulated in opposite directions among the overlapping genes in pathologic cardiac hypert