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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 | Cognitive performance in patients with COPD显示文摘 | Jeroen J.W Liesker Dirkje S Postma Rypko J Beukema Nick H.T ten Hacken Thys van der Molen Roland A Riemersma Ed H van Zomeren Huib A.M Kerstjens | 2003 | Respiratory Medicine2003，，4： | 3 |
| 3 | Cognitive performance in patients with COPD显示文摘 | Jeroen J.W Liesker Dirkje S Postma Rypko J Beukema Nick H.T ten Hacken Thys van der Molen Roland A Riemersma Ed H van Zomeren Huib A.M Kerstjens | 2003 | Respiratory Medicine2003，，4： | 2 |
| 4 | Farming options for the Netherlands explored by multi-objective modeling 显示文摘 | TEN BERGE H F M VAN ITYERSUM M K ROSSING W A H | 2000 | Eur J Agron2000，13，23： | 1 |
| 5 | Polymorphism of milk fat studied by differential scanning calorimetry and real-time X-ray powder diffraction显示文摘 | E ten Grotenhuis G A van Aken K F van Malssen | 1999 | JAOCS1999，76，9： | 1 |
| 6 | Chronic sinusitis in severe asthma is related to sputum eosinophilia显示文摘 | TEN BRINKE A GROOTENDORST D C SCHMIDT J T | 2002 | J Allergy Clin Immunol2002，109，： | 1 |
| 7 | Risk factors of frequentexacerbations in different-to-treat asthma显示文摘 | Ten Brinke A Sterk PJ Masclee AA | 2005 | Eur Respir J2005，26，5： | 1 |
| 8 | On the Bose-Einstein condensation显示文摘 | DEGROOT S R HOOYMAN G J TEN SELDAM C A | 1950 | Proc R Soc London Ser A1950，203，22： | 1 |
| 9 | Thermal behavior of chro- mium electroplating sludge显示文摘 | ESPINOSA D C R TEN RIO J A S | 2001 | Waste Management2001，21，4： | 1 |
| 10 | Reduced ino- tropic reserve and increased susceptibility to cardiac ische- mia/reperfusion injury in phosphocreatine-deficient gua- nidinoacetate-N-methyltransferase-knockout mice显示文摘 | Ten Hove M Lygate CA Fischer A | 2005 | Cir- culation2005，111，19： | 1 |
| 11 | Transgenic expression of pear PGIP in tomato limits fungal colonization 显示文摘 | Powell A L T van Kan J ten Have A | 2000 | Molecular Plant-Microbe Interaction2000，13，： | 1 |
| 12 | Pre- hospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (ON- TIME 2 ) : a multicentre, doubleblind, randomised controlled trial 显示文摘 | van't HOF A W TEN BERG J HEESTERMANS T | 2008 | Lancet2008，372，9638： | 1 |
| 13 | Neovermilia falcigera (Rode, 1898) a deep-and cold-water serpulid polyehaete common in the Mediterranean Plio-Pleistocene 显示文摘 | ZIBROWIUS H TEN HOVE H A | 1987 | Biological Society of Washington Bulletin1987，7，： | 1 |
| 14 | Effect of phtosterols and phtostanols on the solubilization of cholesterol by dietary mixed micelles: An in vitro study显示文摘 | Mel'nikov S M Seiien Ten Hoorn J W M Eijkelenboom A P A M | 2004 | Chemistry and Physics of Lipids2004，127，： | 1 |
| 15 | Serum levels of soluble tumor necrosis factor alpha receptor 2 are linked to insulin resistance and glucose intolerance in children显示文摘 | Gupta A Ten S Anhah H | 2005 | J Pediatr Endocrinol Metab2005，18，： | 1 |
| 16 | Neuronspecific enolase as a marker of brain metastasis in patients with small-cell lung carcinoma显示文摘 | Van de Pol M Tgwijnstra A Ten Velde G P | 1994 | J Neurooncol1994，19，2： | 1 |
| 17 | Assignment of the Smad 7 gene (MADH 7) to human chromosome 18q21.1 by fluorescence in situ hybridization显示文摘 | Roijer E Moren A ten Dijke P | | 0，，： | 1 |
| 18 | Effect of the Newhints home - visits intervention on neonatal mortality rate and care practices in Ghana: a cluster randomised con- trolled trial显示文摘 | Kirkwood B R Manu A ten Asbroek A H | 2013 | Lancet2013，381，9884： | 1 |
| 19 | Dose, volume, and function relationship in parotid salivary glands following conformal and intensity-modulated irradiation of head and neck cancer显示文摘 | Eisbruch A Ten Haken RK Kim HM | 1999 | Int J Radiat Oncol Biol Phys1999，45，3： | 1 |
| 20 | Averse events after protamine administration following cardiopulmonary bypass ininfants and children显示文摘 | SEIFERT H A JOBES D R TEN HAVE T | 2003 | Anesth Analg2003，97，2： | 1 |
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