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 asON phosphorthioate 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. AIM To observe the inhibition of antisense oligonucleotide (asON) phosphorthioate to the tissue inhibitor of metalloproteinase-1 (TIMP-1) gene and protein expression in the liver tissue of immunologically rendered hepatic fibrosis rats. The possibility of reversing hepatic fibrosis through gene therapy was observed. METHODS Human serum albumin (HSA) wasused to attack rats, as hepatic fibrosis model, inwhich asON were used to block the gene andprotein expressing TIMP-1.According to the analysis 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 hybridization for collagen I, III, special staining of collagen fibrils, and electron microscopic examination. RESULTS Hepatic fibrosis could last within 363days in our modified model. The expressinglevel of TiMP-1 was high during hepatic fibrosis process. It has been proven by the immunohistochemical and the electron microscopic examination that the asON phosphorthioate of TIMP-1 could exactly express in vivo, The effect of colchicine was demonstrated to inhibit the expressing level of mRNA and the content of collagen I, III in the liver of experimental hepatic fibrosis rats, However, the electron microscopy research and the pathologic grading of hepatic fibrosisshowed that there was no significant difference between the treatment group and the model group (P> 0.05) .CONCLUSION The experimental rat model of hepatic fibrosis is one of the preferred model estimate of the curative effect of anti-hepaticfibrosis drugs. The asON phosphorthioate of TIMP-1 could block the gene and proteinexpression of TIMP-1 in the liver of experimental hepatic fibrosis rats at the mRNA level. It ispossible to reverse hepatic fibrosis, and it is expected to study a new drug of anti -hepaticfibrosis on the genetic level. Colchicine has verylimited therapeutic effect on hepat ic fibrosis, furthermore, its toxicity and side effects areobvious.