Effect of small interfering RNA targeting Rac1 gene on colony formation of SW480 cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a vector expressing small interfering RNA (siRNA) against Rac1 gene and observe its effect on soft agar colony formation of SW480 cells in vitro.</p><p><b>METHODS</b>Oligos of 64 base pairs for hairpin RNA targeting Rac1 were chemically synthesized and annealed. The siRNA constructs for Rac1, produced by inserting the annealed oligos into the downstream of H1 promoter of linearized pSUPER, were confirmed by restriction digestion and DNA sequencing. The constructed Rac1-siRNA was transfected into SW480 cells and Western blotting was performed to assess the expression and interference efficiency of siRNAs against Rac1.The soft agar colony formation assay was used to study the effect of Rac1 gene silencing on SW480 cells.</p><p><b>RESULTS</b>Restriction digestion and DNA sequencing showed that the siRNA targeting Rac1 gene was successfully constructed. The siRNA could effectively down-regulate the expression of Rac1 in SW480 cells. Soft agar colony formation assay showed that the colony number and diameter of SW480 cells was reduced after siRNA transfection.</p><p><b>CONCLUSION</b>A vector expressing hairpin RNA against Rac1 gene are successfully produced, which significantly reduces the colony numbers and size of SW480 cells in vitro, suggesting that Rac1 plays an important role in the growth of colorectal cancer in vitro.</p>

Effect of partial splenic embolization in prevention of gastroesophageal variceal rebleeding / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of partial splenic embolization (PSE) in prevention of gastroesophageal variceal rebleeding.</p><p><b>METHODS</b>Sixty-two patients with recent gastroesophageal variceal bleeding were treated by PSE with Seldinger technique. All the patients were followed-up for 12 months. The data including peripheral blood cell count, liver function, plasma prothrombin time (PT), portal vein diameter, and appearance of gastroesophageal varices under gastroscopy were collected before and after embolization for statistical analysis.</p><p><b>RESULTS</b>Five days after the operation, the numbers of leucocytes and platelets were significantly increased (P<0.05), and PT was significantly shortened (P<0.05). All the patients showed a good response after PSE with reduced internal diameter of the portal vein and blood flow (P<0.05). Gastroesophageal varices were relieved in all the patients. Rebleeding occurred in 11 patients during the follow-up.</p><p><b>CONCLUSION</b>PSE can be effective in preventing gastroesophageal variceal rebleeding.</p>

Effect of AT-1 alpha receptor gene silencing on nuclear factor-kappaB activity in hepatic Kupffer cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of angiotensin II type-1 (AT-1) alpha receptor gene silencing on nuclear factor-kappaB (NF-kappaB) activity in hepatic Kupffer cells.</p><p><b>METHODS</b>The expression of AT-1 alpha receptors in primary isolated cultured hepatic Kupffer cells was detected by immunohistochemistry. pSilencer/AT-1 alpha receptor siRNA plasmids were transfected into Kupffer cells, which were subsequently exposed to 10(-6) mol/L angiotensin II (Ang II) for 60 min. The changes in the DNA binding activity of NF-kappaB in the cells was assessed using electrophoretic gel mobility shift assay (EMSA).</p><p><b>RESULTS</b>AT-1 alpha receptor expression was detected in Kupffer cells. NF-kappaB DNA binding activity was markedly increased in Kupffer cells after Ang II stimulation, and obviously inhibited by transfectiom with pSilencer/AT-1 alpha receptor siRNA plasmid.</p><p><b>CONCLUSION</b>Ang II stimulation of Kupffer cell results in increased activation of NF-kappaB via AT-1 alpha receptor.</p>

Effect of angiotensin II type 1 receptor and angiotensin-converting enzyme gene silencing on nuclear factor-kappaB activity in hepatic stellate cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of angiotensin II (AngII) type 1 (AT-1) receptor and angiotensin-converting enzyme (ACE) gene silencing on nuclear factor-kappaB (NF-kappaB) activity in hepatic stellate cells (HSCs).</p><p><b>METHODS</b>pSilencer/AT-1 alpha receptor siRNA and pSilencer/ACE siRNA plasmids were transfected into cultured HSC-T6 cells, which were subsequently stimulated by 10(-6) mol/L AngII or ACE inhibitor (ACEI). The DNA binding activity of NF-kappaB in the transfected cells was analyzed using electrophoretic gel mobility shift assay (EMSA).</p><p><b>RESULTS</b>s Gel shift studies showed that stimulation of the HSCs by AngII markedly increased the DNA-binding activity of NF-kappaB, which was inhibited by the transfection with pSilencer/ AT-1 alpha receptor siRNA plasmid or pSilencer/ACE siRNA plasmid.</p><p><b>CONCLUSION</b>AT-1 alpha receptor and ACE gene silencing result in inhibition of NF-kappaB activity in HSCs in vitro.</p>

Effect of angiotensin1-7 on alpha-smooth muscle actin protein expression in rat hepatic stellate cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of angiotensin II and angiotensin1-7 on alpha-smooth muscle actin (alpha-SMA)-induced Ca(2+)-independent pathways mediated by Rho kinase2 in hepatic stellate cells (HSCs).</p><p><b>METHODS</b>HSC-T6 cells were treated with 10 micromol/L of AngII, Ang1-7, AngII +Ang1-7, and Ang1-7+A779. RT-PCR was used to detect the expression of Rho kinase2 (Rock2) in Ca(2+)-independent pathways, and alpha-SMA protein expression was detected by Western blotting.</p><p><b>RESULTS</b>The mRNA expression of Rock2 increased significantly in the cells after AngII treatment (P<0.01), but decreased following Ang1-7 treatment. Ang1-7 treatment significantly reduced alpha-SMA level in AngII-induced cells (P<0.01).</p><p><b>CONCLUSION</b>Ang1-7 can inhibit AngII-induced activation of Rock2 and reduce alpha-SMA expression in HSCs.</p>

Effect of p21-activated kinase-1 on the invasiveness of colorectal carcinoma cells in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of p21-activated kinase-1 (PAK1) gene transfection on the invasiveness of human colorectal carcinoma SW480 cells in vitro.</p><p><b>METHODS</b>SW480 cells in routine culture were transfected with the recombinant plasmid EGFP-C1/PAK1 via Lipofectamine(TM) 2000. The expression of PAK1 protein in SW480 cells was detected using Western blotting, and the changes of the invasiveness of SW480 cells were evaluated using Boyden chamber invasion assay.</p><p><b>RESULTS</b>Forty-eight hours after transfection with pEGFP-C1/ PAK1, the PAK1 protein expression increased significantly in comparison with those in negative and vector control groups. The invasiveness of the SW480 cells was significantly enhanced after the transfection.</p><p><b>CONCLUSION</b>The PAK1 gene transfection can increase the expression of PAK1 in SW480 cells and enhance the invasiveness of the cells. PAK1 can be associated with the invasiveness and metastasis of colorectal carcinoma cells.</p>

Angiotensin II stimulates platelet-derived growth factor-B expression in hepatic stellate cells by activating EGR-1 / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the signal transduction mechanism underlying the effects of angiotensin II (AngII) on extracellular signal-regulated kinase 1/2 (ERK1/2), early growth response-1 (EGR-1) and platelet-derived growth factor-B (PDGF-B) in hepatic stellate cells (HSCs).</p><p><b>METHODS</b>HSC-T6 cells treated with AngII for 10 or 30 min were examined for phospho-P42/44 protein expression using Western blotting. In another experiment, the cells were preincubated for 1 h in the presence of U0126 (an inhibitor of the MAPK/ERK kinase), irbesartan (an AT-1 receptor blocker), or antioxidant-N-acetylcysteine (NAC) prior to AngII exposure, and the protein expression of phospho-P42/44 and PDGF-B were measured with Western blotting. The DNA binding activity of EGR-1 was analyzed using electrophoretic gel mobility shift assay (EMSA), and the expression of PDGF-B was detected immunohistochemically.</p><p><b>RESULTS</b>AngII induced phospho-P42/44 expression in HSC-T6, which was abrogated by U0126 or irbesartan. NAC did not inhibit phospho-P42/44 expression. EMSA showed that AngII exposure of the HSC cells markedly increased EGR-1 DNA binding activity, reaching the maximum after 60 min of exposure followed by progressive declination; irbesartan and U0126 significantly suppressed AngII-induced EGR-1 activity enhancement. ACEI at 1 micromol/L and 10 nmol/L inhibited EGR-1 activity, but ACEI at the concentration of 0.1 nmol/L resulted in enhanced EGR-1 activity. NAC showed no obvious effect in suppressing EGR-1 activity. AngII increased PDGF-B protein level in the HSCs, the effect of which was inhibited by irbesartan. U0126, NAC and ACEI did not attenuate PDGF-BB protein level in the HSCs.</p><p><b>CONCLUSION</b>Stimulation of the HSCs with AngII results in EGR-1 activation via the ERK1/2 pathway, leading to up-regulation of PDGF-B expression.</p>

Detection of interferon-induced transmembrane-1 gene expression for clinical diagnosis of colorectal cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of the interferon-induced transmembrane-1 (IFITM1) gene in colorectal cancer (CRC) tissue and the serum anti-IFITM1 antibody responses of the patients and assess their value in clinical diagnosis of CRC.</p><p><b>METHODS</b>Semi-quantitative RT-PCR was performed to detect IFITM1 mRNA expression in the specimens of normal colonic mucosa, CRC tissue, inflammatory polyps, adenomatous polyps, gastric cancer, esophageal carcinoma and liver cancer tissues. Serum samples were collected from the patients to detect anti-IFITM1 antibody responses using Western blotting. The clinicopathological features of the carcinoma expressing IFITM1 gene were analyzed.</p><p><b>RESULTS</b>IFITM1 mRNA was expressed in 47.4 % (18/38) of the CRC specimens, a rate significantly higher than that in adenomatous polyps [15% (3/20)] and gastric cancer [4.8% (1/21)]; no obvious IFITM1 expression was found in normal colonic mucosa, inflammatory polyp, esophageal carcinoma or liver cancer tissues (P<0.001 or P<0.05). IFITM1 mRNA was strongly expressed in CRC at the expression level of 0.8048-/+0.2273, which was significantly higher than that in adenomatous polyps (0.4447-/+0.0989, P<0.001). No anti-IFITM1 antibody response was detected in healthy human sera, but in the CRC patients, the serum antibody response was detected at the rate of 36.8% (14/38), significantly higher than the rate of 9.5% (2/21) in gastric cancer (P<0.05). No antibody response was detected in esophageal carcinoma, liver cancer, inflammatory polyp or adenomatous polyps. Most of the IFITM1-expressing CRC had a diameter exceeding 5 cm, often invading the serous membrane with metastasis to the lymph nodes and the distant organs; these tumors were identified mostly as well-differentiated adenocarcinoma in Dukes stage C or D.</p><p><b>CONCLUSION</b>IFITM1 gene may play an important role in the pathogenesis, development and metastasis of CRC, and may serve as a potential biomarker for clinical diagnosis of CRC.</p>

Protective effect of curcumin against methotrexate-induced small intestinal damage in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the changes in intestinal mucosal permeability in rats with methotrexate (MTX)-induced small intestinal damage and investigate the protective effects of curcumin.</p><p><b>METHODS</b>The experiment was carried out using 4 groups of rats, namely the normal control group, enteritis model group, sulfasalazine (SASP) group and curcumin group. With the exception of the rats in the normal control group, all rats were subjected to intraperitoneal MTX injection to induce enteritis and received subsequent daily intragastric administration of SASP (100 mg/kg), curcumin (100 mg/kg), or normal saline for 5 days. The disease activity index (DAI), colonic mucosal damage index (CMDI) and histological score (HS) of the rats were evaluated. The levels of diamine oxidase (DAO) and D-lactate were assessed using spectrophotometric assay, and myeloperoxidase (MPO) activity and intracellular adhesion molecule-1 (ICAM-1) protein expression were measured by biochemical and immunohistochemical methods, respectively.</p><p><b>RESULTS</b>Compared with the normal control group, the rats in the model group showed significantly increased DAI, CMDI and HS and levels of DAO, D-lactate, ICAM-1 and MPO. Curcumin treatment resulted in significantly decreased DAI, CMDI, HS and lowered activities of D-lactate, ICAM-1 and MPO in comparison with the model group (P<0.01).</p><p><b>CONCLUSION</b>MTX induces increased mucosal permeability of the small intestines in rats, and curcumin may offer protective effects against MTX-induced rat enteritis by lowering the intestinal mucosal permeability.</p>

Construction and identification of recombinant Lactococcus lactis highly expressing human granulocyte-macrophage colony stimulating factor / 南方医科大学学报

<p><b>OBJECTIVE</b>To transfer human granulocyte-macrophage colony stimulating factor (hGM-CSF) gene into Actococcus lactis and obtain recombinant Lactococcus lactis highly expressing hGM-CSF (LL-CSF).</p><p><b>METHODS</b>The optimized hGM-CSF gene sequence capable of expression in Lactococcus lactis was cloned into the vector pNBC1000, which contained P59 promoter, RBS, MCS, USP45 signal peptide and USP45 stop codon, to generate the recombinant plasmid pNCSF. pNCSF was subcloned into a shuttle vector pTR1001c to acquire the plasmid pTRCSF, which was transferred into Lactococcus lactis to obtain LL-CSF by means of electroporation. SDS-PAGE was used to verify the expression of hGM-CSF protein by the constructed LL-CSF.</p><p><b>RESULTS</b>DNA sequencing and restriction enzyme digestion indicated the successful construction of the recombinant plasmid pNCSF, pTRCSF and the recombinant bacterium LL-CSF that was capable of steady and efficient expression of hGM-CSF as shown by SDS-PAGE.</p><p><b>CONCLUSION</b>The recombinant Lactococcus lactis LL-CSF has been successfully constructed, which can be valuable for studying the biological activity of recombinant hGM-CSF and for evaluating the potential clinical application of the protein.</p>

Intrasplenic heterotransplantation of in vitro cultured human fetal hepatic stem cells for treatment of acute liver injury in mice with severe combined immunodeficiency / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the in vivo colonization, migration, and differentiation of in vitro cultured human fetal hepatic stem cells (HSCs) following intrasplenic transplantation for treatment of acute liver injury in mice with severe combined immunodeficiency (SCID).</p><p><b>METHODS</b>Human fetal HSCs were isolated from the normal fetal liver (16-24 weeks) and purified, and the morphology of HSCs was observed under optical and transmission electron microscopes. The expressions of stem cell markers were examined in these HSCs by means of immunocytochemistry and flow cytometry. The passaged human fetal HSC suspension (0.2 ml) were injected into the spleen of SCID mice with acute liver injury induced by two-third partial hepatectomy, and 15, 30, 60, and 90 days after cell transplantation, immunohistochemistry was performed to examine the location and expressions of human hepatocytes, alpha1-AT and AFP antigen in the spleen and liver of the recipient SCID mice. PAS staining was used to examine the expression of glycogen and RT-PCR employed for detection of the expressions of AFP and albumin mRNA in the spleen of the mice on the scheduled time points.</p><p><b>RESULTS</b>Under optical microscope and transmission electron microscope, most of the HSCs were small, about 1/6 to 1/3 of the size of the hepatocyte, with relatively large nucleus-cytoplasm ratio and only small quantities of endocytoplasmic reticulum, chondriosome, and ribosome. Immunohistochemistry and flow cytometry identified positive expressions of AFP, Thy-1, C-kit, CD34 and CK19 in the HSCs, and after cell transplantation, positive expressions of human hepatocyte, alpha1-AT, and AFP antigen occurred in the liver and spleen of the recipient SCID mice. PAS staining confirmed the presence of glycogenosome in the spleen of the mice following cell transplantation. RT-PCR on days 30, 60, and 90 showed positive expressions of human AFP and albumin mRNA in the spleen of the mice.</p><p><b>CONCLUSION</b>Human fetal HSCs can survive and settle in the spleen and liver, and migrate to the damaged liver of the recipient mice after intrasplenic transplantation, with the capacity of proliferation and differentiation into hepatocytes in the recipient target organs.</p>

Role of Rac1 activation in migration and invasion of colorectal cancer cell line SW480 / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the role of activation of Rac1 in colorectal cancer cell migration and invasion.</p><p><b>METHODS</b>Rac1 L61 plasmid and control plasmid were transfected into colorectal cancer cell line SW480 cells. Pull down assay by Western blotting was carried out to measure the amount of activited Rac1, and transwell permeable supports were used to assess the migration and invasion of SW480 cells with different activitivity of Rac1.</p><p><b>RESULTS</b>The transfection ratio of SW480 cells was more than 80%. Pull down assay showed that the activited Rac1 was significantly higher in the SW480 cells transfected with Rac1 L61 plasmid than that in the control, and the amount of migrating and invasing SW480 cells transfected with Rac1 L61 plasmid in the Transwell permeable supports were significantly more than those in controls (migrating cell numbers: 43 +/- 9 vs. 22 +/- 5, P < 0.01; invasing cell numbers: 73 +/- 13 vs. 38 +/- 1, P < 0.01).</p><p><b>CONCLUSION</b>The activation of Rac1 plays an important role in the migration and invasion of colorectal cancer cells.</p>

Construction of Lactococcus lactis expression vector of recombinant human trefoil factor family 2 / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a Lactococcus lactis expression vector of c-myc-tagged human trefoil factor family 2 (hTFF2) fusion gene to prepare for genetic modification of Lactococcus lactis that can secrete bioactive c-myc-hTFF2 protein.</p><p><b>METHODS</b>Based on the amino sequence of hTFF2 and optimal Lactococcus lactis codon usage, the cDNA of hTFF2 was designed and extended at their 5' ends with a sequence encoding c-myc as the molecular tag. According to the restriction sites of pBluescript II sk (+), the SalI and BamHI sites were arranged at the 5' and 3' ends of the fusion gene respectively. The sequence of the fusion gene c-myc-hTFF2 was designed as 14 oligonucleotides that overlapped with each other, and by means of PCR, all the oligonucleotides were spliced to complete the construction of c-myc-hTFF2 fusion gene. The target gene of c-myc-hTFF2 was inserted into pBluescript II sk (+) to construct the cloning vector pBS-hTFF2 of c-myc-hTFF2 followed by verification by enzyme digestion and DNA sequencing. By digestion of pBS-TFF2 with BamHI/SalI and of pNBC1000 with BamHI/XhoI, we connected c-myc-hTFF2 with pNBC1000 to construct the expression vector c-myc-hTFF2 in E. coli named as pNTFF2. After digestion of pNTFF2 and pTRKH2 with XbaI, the target gene was subcloned into pTRKH2 and the construction of the expression vector pTRTFF2 in Lactococcus lactis was completed. The constructed vector was identified by restriction enzyme digestion.</p><p><b>RESULTS AND CONCLUSION</b>The expression vector pTRTFF2 of c-myc-hTFF2 fusion gene has been successfully constructed. Assembly of oligonucleotides in vitro is an effective means to synthesize the target fusion gene and this prepares the ground for constructing engineered bacterium of Lactococcus lactis.</p>

Screening and preliminary analysis of colorectal carcinoma-associated antigen genes / 南方医科大学学报

<p><b>OBJECTIVE</b>To screen and identify the genes coding for colorectal carcinoma-associated antigen and analyze the bioinformation of their cDNA sequences.</p><p><b>METHODS</b>Immunoscreening of the cDNA phage-display library derived from human colorectal carcinoma was performed with autologous or allogeneic serum antibody from patients with colorectal cancer through SEREX approach. After amplification of the positive phage clones, the phage DNA was extracted and purified with Qiagen kit, and the fragment sizes of the cDNA of positive clones were identified by PCR and EcoR I and Hind III restriction endonucleases. The cDNAs of the positive clones were ligated into pUCm-T vector and sequenced. The bioinformation of cDNA sequences were analyzed against GenBank+EMBL+DDBJ+PDB Sequences Database.</p><p><b>RESULTS AND CONCLUSION</b>Eleven positive clones were obtained after immunoscreening, and the sizes of the cDNA fragments were 1100, 1300, 1000, 2000, 1200, 1200, 700, 900, 600, 1200 and 1000 bp, respectively, representing 9 antigen genes, including 7 with homology with the known genes. Among the 11 obtained positive clones, 3 were the same cDNA having homology with interferon-induced transmembrance protein-1 and possessing anti-proliferation effect; another 6 represented different genes, namely human BAC clone RP11-453E17 whose function have not been cleared, human cartilage-hair hypoplasia region gene responsible for cartilage-hair hypoplasia, human chromosome 5 clone CTD-2030B15 with insertion mutation, human gene similar to anti tumor necrosis factor-alpha antibody light-chain Fab fragment associated with tumor growth, mRNA of human beta-2-microglobulin in relation to tumor cell proliferation, and human aldolase A gene promoting tumor cell proliferation. The other two cDNA sequences were not identified for homology with currently known genes in GenBank, and their functions awaits further investigation.</p>

Aldosterone stimulating PDGF-B expression in HSC via activation of EGR-1 / 中华肝脏病杂志

<p><b>OBJECTIVE</b>It is known that intrahepatic renin-angiotensin-aldosterone system (RAAS) plays a key role in liver fibrogenesis. Aldosterone (Aldo), the principal effector molecule of the RAAS, exerts local effects on cell growth and fibrogenesis. However, the signal transduction mechanisms underlying the effects of Aldo on hepatic fibrogenesis remain to be fully elucidated. The present study aims to investigate the signal transduction mechanism underlying the effects of Aldo on extracellular signal-regulated kinase 1/2 (ERK1/2), early growth response-1 (EGR-1) and on the platelet-derived growth factor-B (PDGF-B).</p><p><b>METHODS</b>In vitro, hepatic stellate cell (HSC)-T6 cell line was treated with Aldo for 10 min, 0.5 h, 1 h, 2 h and 3 h. Protein expression of phospho-p42/44 was detected by Western blot. In addition, HSC-T6 were preincubated for 1 h or not at all with U0126 (an inhibitor of the MAPK/ERK kinase), and antioxidant-N-acetylcysteine (NAC) prior to exposure to Aldo for the indicated times. Protein expressions of phospho-p42/44 and PDGF-B were measured by Western blot. DNA biding activity of EGR-1 was analyzed by electrophoretic gel mobility shift assay (EMSA). By means of immunohistochemistry, expression of PDGF-B was detected.</p><p><b>RESULTS</b>Aldo induced phospho-p42/44 expression could be abrogated by U0126; NAC did not inhibit phospho-p42/44 expression. Gel shift study showed that stimulation of HSC by Aldo markedly increased the EGR-1 DNA binding activity, which was abrogated by U0126, reaching a maximum at 60 minutes, and then declined progressively. NAC did not reduce the EGR-1 activity. Aldo increased the PDGF-B protein level in HSC, which was not attenuated by NAC and U0126.</p><p><b>CONCLUSIONS</b>Stimulation of HSC by Aldo results in activation of EGR-1 via ERK1/2 pathway, leading to up-regulation of PDGF-B expression.</p>

Perindopril attenuates the progression of CCl4-inducing rat hepatic fibrosis / 中华肝脏病杂志

<p><b>OBJECTIVES</b>The aim of the present study was to determine the effects of angiotensin-converting enzyme inhibitor, perindopril, on the progression of rat hepatic fibrosis induced by CCl4.</p><p><b>METHODS</b>Male wistar rats weighting about 250g were treated with perindopril (2mg/kg, daily gavage), except for model group and control group. After 4, 6 weeks, morphological examination was based on microscopy. RT-PCR was utilized to detect gene expression of angiotensin II type 1 receptor (AT1 receptor) in the liver. Meanwhile, the protein expressions of AT1 receptor, transforming growth factor beta 1 (TGF-beta1) and platelet-derived growth factor-BB (PDGF-BB) in liver tissue were examined by Western blot. The activity of matrix metalloproteinase-2 (MMP-2) was assessed by zymography. Serum laminin (LN) and hyaluronic acid (HA) were measured using radio-immunity technique.</p><p><b>RESULTS</b>RT-PCR and Western blot revealed that there was a up-regulation in AT1 receptor expression in model group compared with control group. Perindopril treatment significantly reduced mean fibrosis score, messenger RNA and protein levels of AT1 receptor, protein levels of TGF-beta1 and PDGF-BB, Serum levels of HA and LN, and MMP-2 activity.</p><p><b>CONCLUSION</b>These results suggest that angiotensin II may play an important role in fibrosis of liver. Perindopril may have a inhibiting effect on CCl4-induced hepatic fibrogenesis of rat.</p>