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| 1 | Inhibiting effect of antisense oligonucleotides phosphorthioate on gene expression of TIMP-1 in rat liver fibrosis显示文摘AIM To observe the inhibition of antisenseoligonucleotides (asON) phosphorthioate to thetissue inhibitors metalloproteinase-1 (TIMP-1)gene and protein expression in the liver tissue ofimmunologically induced hepatic fibrosis rats.The possibility of reversing hepatic fibrosisthrough gene therapy was observed.METHODS Human serum albumin (HSA) wasused to attack rats, as hepatic fibrosis model, inwhich asONs were used to block the gene andprotein expressing TIMP-1. According to theanalysis of modulator, structure protein, codingseries of TIMP-1 genome, we designed fourdifferent asONs. These asONs were injected intothe hepatic fibrosis models through coccygealvein. The results was observed by RT-PCR formeasuring TIMP-1 mRNA expression,immunohistochemistry and in situ hybridizationfor collagen Ⅰ, Ⅲ, special staining of collagenfiber, and electron microscopic examination.RESULTS Hepatic fibrosis could last within 363days in our modified model. The expressinglevel of TIMP-1 was high during hepatic fibrosisprocess. It has been proved by theimmunohistochemical and the electronmicroscopic examination that the asONphosphorthioate of TIMP-1 could exactly expressin vivo. The effect of colchicine wasdemonstrated to inhibit the expressing level ofmRNA and the content of collagen Ⅰ, Ⅲ in theliver of experimental hepatic fibrosis rats.However, the electron microscopy research andthe pathologic grading of hepatic fibrosisshowed that there was no significant differencebetween the treatment group and the modelgroup (P>0.05).CONCLUSION The experimental rat model ofhepatic fibrosis is one of the preferable modelsto estimate the curative effect of anti-hepaticfibrosis drugs. The asON phosphorthioate ofTIMP-1 could block the gene and proteinexpression of TIMP-1 in the liver of experimentalhepatic fibrosis rats at the mRNA level. It ispossible to reverse hepatic fibrosis, and it isexpected to study a new drug of anti-hepaticfibrosis on the genetic level. Colchicine has verylimited therapeutic effect on hepatic fibrosis,furthermore, its toxicity and side effects areobvious. | Qing He Nie Yong Qian Cheng Yu Mei Xie Yong Xing Zhou Yi Zhan Cao The Center of Infectious Disease Diagnosis and Treatment of PLA,Tangdu Hospital,Forth Military Medical University,Xi’an 710038,Shaanxi Province,ChinaDr,Qing He Nie graduated from Qinghai Medical College as a doctor in 1983,got master degree at Beijing 302 Army Hospital in 1993,got doctor degree at the Third Military Medical University in 1998,engaged in postdoctoral research at the Fourth Military Medical University from 1998 to 2000,now an associate professor,specialized in clinical and experimental research of infectious diseases,had more than 90 papers published,coauthor of ten books,first author of one book. | 2001 | World Journal of Gastroenterology2001，7，3： | 73 |
| 2 | Evidence That the Diabetes Gene Encodes the Leptin Receptor: Identification of a Mutation in the Leptin Receptor Gene in db / db Mice显示文摘 | Hong Chen Olga Charlat Louis A Tartaglia Elizabeth A Woolf Xun Weng Stephen J Ellis Nathan D Lakey Janice Culpepper Karen J More Roger E Breitbart Geoffrey M Duyk Robert I Tepper Jay P Morgenstern | 1996 | Cell1996，，3： | 2 |
| 3 | Systematic design of adaptive controllers for feedback linearizable systems 显示文摘 | KANELLAKOPOULOS I KOKOTOVIC P V MORE A S | 1991 | IEEE Transactions on Automatic Control1991，36，： | 1 |
| 4 | Decentralized control of linear multivariable systems显示文摘 | Corfmat J P Mores A S | 1976 | Automatica1976，12，3： | 1 |
| 5 | Low temperature growth of aligned ZnO nanowires and their application as ? eld emission cathodes显示文摘 | SHEINI F J JOAG D S MORE M A | 2010 | Materials Chemistry and Physics2010，210，： | 1 |
| 6 | Systematic design of adaptive controllers for feedback linearizable systems显示文摘 | KANELLAKOPOULOS I KOKOTOVIC P V MORES A S | 1991 | IEEE Trans on Automatic Control1991，36，11： | 1 |
| 7 | Prevalence, distribution, and molecular characterization of Salmonella recovered from swine finishing herds and a slaughter facility in Santa Catarina, Brazil显示文摘 | Kich JD Coldebella A Mores N | 2011 | Int J Food Microbiol2011，151，3： | 1 |
| 8 | Bayesian linearized AVO inversion显示文摘 | BULAND A MORE H | 2003 | Geophysics2003，68，1： | 1 |
| 9 | Modification of bent angle of mechanically formed stainless steel sheets by laser forming显示文摘 | CHAKRABORTY S S MORE H RACHERLA V NATH A K | 2015 | Journal of Materials Processing Technology2015，222，： | 1 |
| 10 | Plant disease resistance genes encode members of an ancient and diverse protein family with the nucleotidebindig superfamily显示文摘 | Meyers B C Dickerman A W Michel more R W | 1999 | Plant J1999，，20： | 1 |
| 11 | A new quation equation of state (QEOS) for hot dense matter显示文摘 | More R M Warren K H Young D A | | 0，，： | 1 |
| 12 | A- neural-network approach for prediction of software develop- ment faults 显示文摘 | KHOSHGOFI'AAR T M PANDYA A S MORE H B | 1992 | IEEE Computer1992，17，8： | 1 |
| 13 | A Murine Model of Streptococuus Suis Type2 Meningitis in the Pigs显示文摘 | Williams A Black More W Alexander T | 1998 | Rev Vet Sci1998，45，： | 1 |
| 14 | Influence of sulfur,platinum,and hafnium on the oxidation behavior of CVD NiA1 bond coatings显示文摘 | Haynes J A Pint B A More K L | 2002 | Oxidation of Metals2002，58，56： | 1 |
| 15 | Starch and protein quality requirements of Japanese alkaline noodle (Ramen)显示文摘 | Crosbie G B Ross A S More T | 1999 | Cereal Chemistry1999，76，3： | 1 |
| 16 | A new quotidian equation of state(QEOS) for hot dense matter显示文摘 | More R M Warren K H Young D A | 1988 | PhysicsofFluids1988，31，10： | 1 |
| 17 | Expression Pattern of Theneu(NGL) Gene Encoded Growth Factor Receptor(P185 neu)in Normal and Transformed Epithelial Tissues of the Digestive Tract 显示文摘 | Chen J A Weiner D B More K F | 1989 | Oncogene1989，4，1： | 1 |
| 18 | Oesophageal rhabdomyoma 显示文摘 | Roberts F Kirk A J More IA | 2000 | J Clin Pathol2000，53，7： | 1 |
| 19 | Heat shock proteins as activators of the innate immune system显示文摘 | Wallin RPA Lundqvist A More SH | 2002 | Trends hnmunol2002，23，： | 1 |
| 20 | Attitudes of massachusetts hunters显示文摘 | MORE T A | 1973 | Transactions of the North American Wildlife and Natural Resource Conference1973，38，： | 1 |
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