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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 | Dynamic Window Reduction for the Multiple Depot Vehicle Scheduling Problems with Time Windows显示文摘 | HAD JAR A SOUMIS F | 2009 | Computers & Operations Research2009，36，7： | 1 |
| 3 | Resolution of quantitative traits into Mendelian factors by using a complete linkage map of restriction fragment length polymorphisms显示文摘 | Paterson A H Lander E S Had J D | 1991 | Nature1991，335，： | 1 |
| 4 | Lung mechanics in rachitic rats显示文摘 | Gauhier C Had A Balmain N Cuisinier-Gleizes P Mathieu H | 1984 | Am Rev Respir Dis1984，130，6： | 1 |
| 5 | Microchip devices for performing enzyme assays 显示文摘 | Had A G Raymond D E Ramsey J M | 1997 | Anal Chem1997，69，： | 1 |
| 6 | Adaptive median filters:new algorithms and results显示文摘 | Hwang H Hadded R A | 1995 | IEEE Transactions on Image Processing1995，4，： | 1 |
| 7 | Robust fuzzy tracking control for robotic manipulators显示文摘 | H F Ho Y K Wong A B Had | 2007 | Simulation Modeling Practice and Theory2007，15，7： | 1 |
| 8 | B-type natriuretic peptide and adiponectin releases in rat model of myocardial damage induced by isoproterenol administration显示文摘 | Hasi'c S Had?ovi'c-D?uvo A Jadri'c R | 2013 | Bosn J Basic Med Sci2013，13，4： | 1 |
| 9 | TDMA-based MAC protocols for vehicular ad hoc networks: a survey, qualitative analysis and open research issues显示文摘 | HADDED M P LAOUITI A | 2015 | IEEE Communications Surveys & Tutorials2015，17，4： | 1 |
| 10 | Determination of phenol, m-cresol and o-cresol in transformer oil by HPLC method显示文摘 | Vrsaljko D Haramija V Hadž i-Skerlev A | 2012 | Electric Power Systems Research2012，93，： | 1 |
| 11 | Persistent hyperglycemia in severe traumatic brain injury: an independent predictor of outcome 显示文摘 | Salim A Had izacharia P Dubose J | 2009 | Am Surg2009，75，1： | 1 |
| 12 | Left-handed metamaterials with saturable nonlinearity显示文摘 | Maluckov A Hadievski L Lazarides N | 2008 | Phys Rev E2008，77，04： | 1 |
| 13 | More on modifications and improvements of classical iterative scheme as for M matrix显示文摘 | HAD JID IM OS A NOU TSOS D TZOUM AS M | 2003 | Liner Algebra Appl2003，364，： | 1 |
| 14 | Impact of western flower thrips (Thysanoptera: Thripidae) on growth, photosynthesis and productivity of greenhouse sweet pepper显示文摘 | SHIPP J L HAD X PAPADOPOULOS A P | 1998 | Scientia Horticulturae1998，72，： | 1 |
| 15 | ReDs-a Dynamic planning,Scheduling, and Control System for Manufacturing 显示文摘 | HAD A VI K HSU W L VOLGT K | 1990 | Journalof Manufacturing Systems1990，32，4： | 1 |
| 16 | Barriers to innovation for SMEs in a small less developed country (Cyprus) 显示文摘 | HAD JIMANOLIS A | 1999 | Technovation1999，19，9： | 1 |
| 17 | Nephrotic syndrome preceding psoriasis in children显示文摘 | Menou S Had P | 2007 | Pediatr Nephrol2007，22，： | 1 |
| 18 | 显示文摘 | Hadding A Kattschmidt B Kaltschmidt C | 2004 | Biochem Biophys Acta2004，1691，1： | 1 |
| 19 | Rapid diagnosis of tuberculosis in various biopsy and body fluid specimens by the amplifier mycobacterium tuberculosis polymerase chain test显示文摘 | S HAD S H MILLER A ANTHONY M | 1998 | Chest1998，113，1： | 1 |
| 20 | Failure probability evaluation of passive system using fuzzy Monte Carlo simulation显示文摘 | Had Prasad M Gaikwad A J Srividya A | 2011 | Nuclear Engineering and Design2011，，241： | 1 |
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