Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-β/Smad Signaling / 中国结合医学杂志

OBJECTIVE@#To observe the effect of amygdalin on liver fibrosis in a liver fibrosis mouse model, and the underlying mechanisms were partly dissected in vivo and in vitro.@*METHODS@#Thirty-two male mice were randomly divided into 4 groups, including control, model, low- and high-dose amygdalin-treated groups, 8 mice in each group. Except the control group, mice in the other groups were injected intraperitoneally with 10% carbon tetrachloride (CCl4)-olive oil solution 3 times a week for 6 weeks to induce liver fibrosis. At the first 3 weeks, amygdalin (1.35 and 2.7 mg/kg body weight) were administered by gavage once a day. Mice in the control group received equal quantities of subcutaneous olive oil and intragastric water from the fourth week. At the end of 6 weeks, liver tissue samples were harvested to detect the content of hydroxyproline (Hyp). Hematoxylin and eosin and Sirius red staining were used to observe the inflammation and fibrosis of liver tissue. The expressions of collagen I (Col-I), alpha-smooth muscle actin (α-SMA), CD31 and transforming growth factor β (TGF-β)/Smad signaling pathway were observed by immunohistochemistry, quantitative real-time polymerase chain reaction and Western blot, respectively. The activation models of hepatic stellate cells, JS-1 and LX-2 cells induced by TGF-β1 were used in vitro with or without different concentrations of amygdalin (0.1, 1, 10 µmol/L). LSECs. The effect of different concentrations of amygdalin on the expressions of liver sinusoidal endothelial cells (LSECs) dedifferentiation markers CD31 and CD44 were observed.@*RESULTS@#High-dose of amygdalin significantly reduced the Hyp content and percentage of collagen positive area, and decreased the mRNA and protein expressions of Col-I, α-SMA, CD31 and p-Smad2/3 in liver tissues of mice compared to the model group (P<0.01). Amygdalin down-regulated the expressions of Col-I and α-SMA in JS-1 and LX-2 cells, and TGFβ R1, TGFβ R2 and p-Smad2/3 in LX-2 cells compared to the model group (P<0.05 or P<0.01). Moreover, 1 and 10 µmol/L amygdalin inhibited the mRNA and protein expressions of CD31 in LSECs and increased CD44 expression compared to the model group (P<0.05 or P<0.01).@*CONCLUSIONS@#Amygdalin can dramatically alleviate liver fibrosis induced by CCl4 in mice and inhibit TGF-β/Smad signaling pathway, consequently suppressing HSCs activation and LSECs dedifferentiation to improve angiogenesis.

Research Progress on Mechanism of Yiguanjian Intervention in Liver Cirrhosis / 中国实验方剂学杂志

Liver cirrhosis caused by the repeated action of one or more causes is a pathological stage characterized by diffuse fibrosis of the liver parenchyma， formation of false lobules and regenerative nodules， portal hypertension which caused by abnormal blood vessels inside and outside the liver. The progression of cirrhosis to decompensation is characterized by severe liver damage， with ascites， gastroesophageal varices bleeding， hepatic encephalopathy and other complications， and most of the treatments are symptomatic， with high mortality and poor prognosis. At present， the traditional Chinese medicine treatment of decompensated cirrhosis can not only effectively improve liver function， but also significantly improve the 5-year survival rate of patients， which suggests that Chinese medicine has potential advantages in preventing and treating end-stage liver disease， and promoting liver cirrhosis tissue reconstruction. Modern Chinese medicine doctors believe that liver cirrhosis is mainly caused by Qi Yin deficiency （liver， spleen， kidney），internal invasion of damp-heat epidemic toxin， and collateral stasis. Deficiency of liver and kidney Yin is a common symptom of decompensated cirrhosis. Yiguanjian， one of Kidney-Nourishing and Liver-Replenishing decoction in traditional Chinese medicine ， is the representative prescription for modern clinical treatment of chronic liver disease with "deficiency of liver and kidney Yin" syndrome. Yiguanjian， created by WEI Yu-zhen （WEI Zhi-xiu）in the Qing Dynasty， Contained in "Xu Ming Yi Lei An ". Clinical studies show that Yiguanjian can effectively improve liver function in patients with liver cirrhosis， promote ascites resolution， and reduce the occurrence of hepatic encephalopathy and other related complications. Experimental research has suggested that Yiguanjian has the characteristics of multi-path， multi-level， and multi-target comprehensive regulation. The mechanism of prevention and treatment of liver cirrhosis may be mainly related to anti-oxidative stress， improving liver inflammation， improving liver cell biosynthesis， inhibiting hepatic stellate cell activation， reducing collagen deposition， improving sinusoidal vascularization and promoting liver cell regeneration. This paper reviews the progress of clinical and experimental research of Yiguanjian in the treatment of liver cirrhosis in the past 5 years， to provide some references for the clinical application and in-depth study of Yiguanjian.

Xiayuxue Decoction (symbols; see text) attenuates hepatic stellate cell activation and sinusoidal endothelium defenestration in CCl4-induced fibrotic liver of mice / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of ancient Chinese medical formula Xiayuxue Decoction ([symbols; see text], XYXD) on activation of hepatic stellate cells (HSCs) and defenestration of sinusoidal endothelial cells (SECs) in CCl4-induced fibrotic liver of mice.</p><p><b>METHODS</b>High performance liquid chromatography was used to identify the main components of XYXD and control the quality of extraction. C57BL/6 mice were induced liver fibrosis by CCl4 exposure and administered with XYXD for 6 weeks simultaneously. Liver tissue was investigated by hematoxylin-eosin and Sirius-red staining. Sinusoidal fenestrations were observed by scanning electronic microscopy and fluorescent immunohistochemistry of PECAM-1 (CD31). Whole liver lysates were detected of α-smooth muscle actin (α-SMA) and type-I collagen by Western blot. Primary rat HSCs-T6 cells were analyzed by detecting α-SMA, F-actin, DNA fragmentation through confocal microscopy, Western blot, terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay and cellomics arrayscan, respectively.</p><p><b>RESULTS</b>Amygdalin and emodin in XYXD were identified. XYXD (993 mg/kg) inhibited Sirius red positive area up to 70.1% (P<0.01), as well as protein levels of α-SMA and type-I collagen by 42.0% and 18.5% (P<0.05) respectively. In vitro, XYXD (12.5 μg/mL, 50 μg/mL) suppressed the activation of HSCs and reversed the myofibroblastic HSCs into quiescent, demonstrated as inhibition of fluorescent F-actin by 32.3% and 46.6% (P<0.05). Besides, XYXD induced the apoptosis of HSC-T6 cells by 20.0% (P<0.05) and 49.5% (P<0.01), evidenced by enhanced TUNEL positivity. Moreover, ultrastructural observation suggested XYXD inhibited defenestration of SECs, which was confirmed by 31.1% reduction of protein level of CD31 (P<0.05).</p><p><b>CONCLUSIONS</b>XYXD inhibited both HSCs activation and SECs defenestration which accompany chronic liver injuries. These data may help to understand the underlying mechanisms of XYXD for prevetion of chronic liver diseases.</p>

Mechanism of hepatocyte apoptosis in rats with liver fibrosis induced by lipogenic methionine-choline-deficient diet / 中华病理学杂志

<p><b>OBJECTIVE</b>To clarify the effects of endoplasmic reticulum stress (ER stress) and mitogen-activated protein kinase (MAPK) on hepatocyte apoptosis in rats with non-alcoholic fatty liver fibrosis induced by methionine-choline-deficient diet (MCDD).</p><p><b>METHODS</b>Nonalcoholic steatohepatitis with advanced fibrosis was induced in rats by giving a MCDD for 10 weeks (group M). A methionine-choline-control diet (MCCD) instead of MCDD was given for the last 2 weeks to the experimental group (group R). Steatosis, fibrosis and inflammation were determined by tissue staining. The activation of hepatic stellate cells and oxidative stress were determined by immunostaining, immunoblotting or real time-PCR (RT-PCR), respectively. Hepatocyte apoptosis was determined by TUNEL staining. Expressions of glucose-regulated protein 78 (GRP78), caspase-12, caspase-7, cleaved caspase-7, caspase-3, cleaved caspase-3, and caspase-9 were evaluated to clarify the presence of ER stress. Expressions of c-Jun, ERK1/2, p-ERK1/2 were evaluated to clarify the states of MAPK signaling.</p><p><b>RESULTS</b>Changing the diet from MCDD to MCCD triggered the reduction of fat in hepatocytes, a decrease in inflammatory response, oxidative stress, and fibrosis. The protein expressions of ERP78, caspase-12, caspase-7, and cleaved caspase-7 were increased significantly in group M compared with normal control group (group N, P < 0.05 or P < 0.01), the mRNA expressions of ERP78, caspase-12, and caspase-7 were also increased significantly in group M compared with group N (3.03 ± 0.41 vs 2.12 ± 0.37, 1.86 ± 0.36 vs 0.78 ± 0.20, and 2.38 ± 0.19 vs 1.84 ± 0.13, respectively, P < 0.05 or P < 0.01), while they recovered immediately in group R. In contrast, the protein levels of caspase-3, cleaved caspase-3 and mRNA expressions of caspase-3 and caspase-9 revealed no significant differences in three groups (P > 0.05). The mRNA expressions of c-Jun and protein levels of ERK1 and p-ERK1 were increased significantly in group M compared with group N (P < 0.01), while they recovered immediately after changing the diet from MCDD to MCCD.</p><p><b>CONCLUSIONS</b>ER stress plays a role in the development and regression of non-alcoholic fatty liver fibrosis induced by MCDD, however, ER stress-related caspase-12 pathway may not be the main mechanism of hepatic apoptosis, and MAPK signaling may play an important role in hepatic apoptosis in the model.</p>

Dynamic change of lipid peroxidation-related protein expression and the intervention effects of Yiguanjian decoction in a rat model of CCl4-induced liver fibrosis / 中华肝脏病杂志

To investigate the dynamic change of lipid peroxidation-related protein expression and the intervention effects of Yiguanjian (YGJ) Decoction on liver fibrosis induced by CCl4 in rat. Fifty-seven male Wistar rats were randomly divided into a liver fibrosis group (n = 39) and a normal group (n = 18). The liver fibrosis was treated with peritoneal injection of 50% CCl4 for nine weeks. At the end of weeks 3 and 6 of CCl4 treatment, six rats were sacrificed to assess the status of liver fibrosis. At the end of week 7, the remaining -fibrotic rats were randomly divided into an untreated model group (M, n=15) and a YGJ-treated group (n = 12). The YGJ group was administered daily, oral YGJ Decoction for three weeks, concomitant with continued CCl4 treatment. The M group and normal group received the same treatment oral regimen and volume of distilled water. At the end of week 8, four rats in group M were sacrificed to observed the fibrosis status. At the end of week 9, the fibrotic rats were sacrificed for sampling. Liver function, histological changes, contents of hydroxyproline (Hyp) and malondialdehyde (MDA), activity of super oxidase dismutase (SOD) and L-glutathione (GSH), protein expression of heat shock protein (HSP)70, heme oxygenase (HO)-1, transferrin, peroxiredoxin (Prxd) 6 and liver fatty acid binding protein (L-FABP) were detected. Compared with normal group-, the MDA content was increased significantly in M group at week 6 (M: 4.23+/-0.45 nmol/mg vs. normal: 2.22+/-0.59 nmol/mg, F = 60.13, P less than 0.01) and week 9 (M: 6.29+/-1.23 nmol/mg vs. normal: 2.22+/-0.59 nmol/mg, F = 66.99, P less than 0.01), but the SOD activity was decreased significantly at the same time points [week 6: (M: 196.94+/-39.20 U/mg vs. normal: 264.50+/-30.44 U/mg, F = 11.12, P less than 0.01]); [week 9: (M: 152.2+/-51.65 U/mg vs. normal: 264.50+/-30.44 U/mg, F = 23.11, P less than 0.01)], as were the GSH content [week 6: (M: 48.47+/-7.27 nmol/mg vs. 60.74+/-9.04 nmol/mg, F = 6.71, P less than 0.05]]; [week 9: (M: 37.89+/-9.01 nmol/mg vs. 60.74+/-9.04 nmol/mg, F = 24.06, P less than 0.01]]. Compared with group M at week 9, the YGH-treated model group had markedly decreased MDA (YGJ: 4.25+/-0.86 nmol/mg vs. M: 6.29+/-1.23 nmol/mg, F = 19.52, P less than 0.01], but significantly increased SOD (YGJ: 198.35+/-46.48 U/mg vs. 152.21+/-51.65 U/mg, F = 4.65, P less than 0.05] and GSH (YGJ: 53.73+/-7.54 nmol/mg vs. M: 37.89+/-9.01 nmol/mg, F = 19.23, P less than 0.01). Compared to normal rats at week 9, group M had significantly higher protein levels of HSP70 (normal: 1.21+/-0.06 vs. M: 0.58+/-0.07, F = 166.87, P less than 0.01) and HO-1 (normal: 1.11+/-0.06 vs. M: 0.58+/-0.06, F = 123.96, P less than 0.01), but significantly decreased levels of Prxd6 (normal: 0.04+/-0.05 vs. M: 1.49+/-0.05, F = 1215.85, P less than 0.01), transferrin (normal: 0.67+/-0.03 vs. M: 1.67+/-0.04, F = 301.35, P less than 0.01), and L-FABP (normal: 0.24+/-0.02 vs. M: 1.44+/-0.14, F = 219.05, P less than 0.01). Compared to group M at week 9, the YGJ treatment group showed significantly reduced HSP70 (YGJ: 0.82+/-0.04 vs. M: 1.21+/-0.06, F = 92.31, P less than 0.01) and HO-1 (YGJ: 0.90+/-0.04 vs. 1.11+/-0.06, F = 26.89, P less than 0.01), but significantly increased Prxd6 (YGJ: 0.88+/-0.11 vs. 0.04+/-0.05, F = 150.17, P less than 0.01), transferrin (YGJ: 1.36+/-0.13 vs. 0.24+/-0.02, F = 237.19, P less than 0.01), and L-FABP (YGJ: 1.04+/-0.12 vs. 0.67+/-0.03, F = 27.53, P less than 0.01). YGJ treatment of fibrotic liver rats reduces lipid peroxidation damage by preventing generation of oxidizing substances.

Effect of reducing injection on HFMD in children: a randomized controlled trial / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the clinical effects of Reduning Injection on ordinary hand, foot and mouth disease (HFMD) in children.</p><p><b>METHODS</b>76 children with confirmed diagnosis of HFMD were randomly assigned to 3 groups by the center randomization method, i.e., the Western medicine group (WM, 24 cases, treated with Ribavirin Injection or antibiotics), the Reduning Injection group (RI, 26 cases, treated with Reduning Injection), and the combination group (26 cases, treated with the combination of Reduning injection with Ribavirin Injection or antibiotics). The therapeutic course lasted for 3 to 7 days. A 3-day follow-up study was performed by the end of the treatment. The blood routines, the liver function, the renal function, the fasting blood glucose, the pyretolysis effect initiating time, the time for the body temperature recovery, and the rash subside time were observed in the three groups.</p><p><b>RESULTS</b>(1) Of 76 patients, 13 dropped out, with the final effective case being 63. Of them, there were 19 cases in the WM group, 22 in the RI group, and 22 in the combination group. (2) Compared with the WM group, the pyretolysis effect initiating time and the time for the body temperature recovery were both significantly shortened in the RI group and the combination group (P<0.05, P<0.01). (3) There was no significant difference in the rash subside time among the three groups (P>0.05). But there was shortening tendency in the RI group and the combination group. (4) One child in the RI group dropped out from this study due to a mild rash, and no adverse drug reaction occurred in the other two groups.</p><p><b>CONCLUSIONS</b>RI had some advantages in treatment of HFMD such as fasting pyretolysis effect initiating time, shorter time for the body temperature recovery, higher safety. Besides, it also could accelerate the subside of skin rashes to some extent.</p>

Effect of Xiaozheng Rongmu powder for the treatment of liver cirrhosis in rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the therapeutic effect of Xiaozheng Rongmu Powder (XRP) for the treatment of progressive CCl4-induced liver cirrhosis in rats.</p><p><b>METHODS</b>Rat liver cirrhosis model was established by subcutaneous injection of 50% CCl4-olive oil 2 mL/kg twice a week for 12 weeks. Experimental rats were divided into the control group treated by saline and the two treatment groups, treated with XRP and Xiaochaihu Decoction, respectively, with the treatment starting from the 9th week of modeling. Rats were sacrificed at the terminal of experiment, the death rate, character of ascites, liver histological changes, liver function, mRNA expression of hepatocyte mitosis and the liver fibrosis associated markers in rats were observed.</p><p><b>RESULTS</b>At the end of the 8th week of modeling, serum levels of ALT, AST and TBil were increased, and Alb decreased significantly in rats (P < 0.01), cirrhosis formation with ascites could be seen in all rats. Meantime, levels of vascular smooth muscle alpha-actin, transforming growth factor-beta1, collagen I A2, tumor necrosis factor-alpha, tissue inhibitor of melalloproteinase-1 mRNA increased, while matrix melalloproteinase-13 mRNA were decreased significantly (P < 0.01), with visible liver proliferation to some extents. Further changes of above-mentioned abnormalities and clear suppression of hepatocytes mitosis were found in the modeled rats at the end of the 12th week. As compared to those occurred in the control group, changes in the XRP treated group were significantly milder at the corresponding duration, and clearly active hepatocytes mitosis was shown.</p><p><b>CONCLUSION</b>XRP, a Chinese drug with the effect of dissolving phlegm, removing stasis and supplementing qi, could reverse the progress of cirrhosis formation induced by CCl4, and it brings potential new hope for the treatment of advanced cirrhosis by Chinese medicine.</p>

Involvement of endoplasmic reticulum stress in development of fatty liver fibrosis induced by methionine-choline-deficient diet in rats / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study role of endoplasmic reticulum stress in the development of fatty liver fibrosis induced by methionine-choline-deficient diet in rats.</p><p><b>METHODS</b>Non-alcoholic steatohepatitis was induced by 10 weeks- methionine-choline-deficient diet (MCDD), Markers of endoplasmic reticulum stress were determined by immunoblotting and real-time PCR.</p><p><b>RESULTS</b>The number of apoptotic hepatocytes, The expression levels of endoplasmic reticulum stress markers were increased significantly in MCDD group compared to control group (probability value less than 0.05 or probability value less than 0.01), while ratio of hepatocyte proliferation/apoptosis was decreased in MCDD group (probability value less than 0.01). The number of hepatocytes apoptosis, and the expression levels of endoplasmic reticulum stress markers were decreased significantly 2 weeks after the feeding with normal diet in MCDD group (probability value less than 0.05 or probability value less than 0.01).</p><p><b>CONCLUSION</b>MCDD induces endoplasmic reticulum stress and fibrosis in rats.</p>

Clinical features and prognosis of the mild cases of pandemic influenza H1N1 virus infection / 中华预防医学杂志

<p><b>OBJECTIVE</b>Analyze the clinical characteristics of the mild cases of pandemic influenza H1N1 virus infection, as well as the relationship of clinical characteristics and patient genders.</p><p><b>METHODS</b>A total of 245 influenza A (H1N1) patients confirmed by viral nucleic acid detection were included in the study. The patients' personal information, signs and symptoms, lab and iconography data, disease course, negative seroconversion duration of new influenza A (H1N1) viral nucleic acid after antiviral treatment and hospitalization stay were analyzed. Measurement data were analyzed using one-way analysis of variance (ANOVA) by software SPSS 11.5. P < 0.05 was defined as statistically significant.</p><p><b>RESULTS</b>(1) Among the 245 patients, 130 were males and 115 were females, yielding a sex ratio of 1.13:1. Almost 52.0% (127/245) of the patients came from Australia, and 64.5% (158/245) were between 18 and 40 years old. (2) Clinical manifestations included fever (98.4%, 241/245), cough (80.8%, 198/245) and throat congestion (95.9%, 235/245), and lab findings were characterized by elevated C-reaction protein (CRP, 71.0%, 174/245) and neutrophil (52.2%, 128/245). (3) Female patients had significantly lower serum Prealbumin (pre-A) levels than male patients [(245.04 ± 75.3) vs (273.34 ± 92.18) mg/L, F = 5.55, P = 0.019]. (4) The patients' serum CRF levels significantly decreased after the treatment [(4.06 ± 3.47) vs (14.54 ± 14.68) mg/L, F = 6.18, P = 0.016], while the levels of CD3, CD4 and CD8 were significantly increased after treatment [(1451.23 ± 443.97) vs (819.97 ± 375.75) cell/µl, F = 32.61, P = 0.000; (771.33 ± 251.92) vs (435.36 ± 215.35) cell/µl, F = 44.43, P = 0.000; (593.16 ± 237.19) vs (342.47 ± 180.12) cell/µl, F = 28.518, P = 0.000, respectively]. (5) Approximately 30.6% (75/245) of the patients had abnormal signs on chest CT iconography, and 22.0% (54/245) had obvious signs indicating pneumonia. The average disease course was (3.9 ± 1.2) days, the average hospitalization stay was (5.0 ± 1.4) days, and the negative seroconversion duration of the mRNA after antiviral treatment was (3.8 ± 1.4) days.</p><p><b>CONCLUSION</b>The influenza A (H1N1) virus was characterized by fever, cough and throat congestion, with elevated CRP and neutrophil being the most significant lab findings. The influenza A (H1N1) strain was able to affect multiple organs, including being able to affect hepatic synthesis of pre-A as well as immune functioning. The influenza A (H1N1) influenza virus strain was mild clinically, with short disease course and good prognosis.</p>

Study on pathogenesis of CCl4 induced cirrhosis formation in rats based on the recipe used / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the recipe-based pathogenesis and effects of Xiayuxue Decoction (XD), Yinchenhao Decoction (YcD), Yiguanjian Decoction (YgD) and Huangqi Decoction (HD) on carbon tetrachloride (CCl4) induced liver cirrhosis formation in rats on the basis of the recognition of basic pathogenesis of liver cirrhosis in TCM and train of thoughts of detecting the TCM syndrome by recipe.</p><p><b>METHODS</b>Model rats of liver cirrhosis were established by subcutaneous injecting of 100% CCl4 3ml/kg followed by 50% CCl4 olive solution 2ml/kg, twice a week for 12 weeks. They were randomly divided into the model group, the XD treated group, the YcD treated group, the YgD treated group and the HD treated group. Rats in the three treated group received the treatment starting from the 9th week of modeling with the corresponding decoctions. All animals were sacrificed by the end of the 12th week, and their hepatic function, liver pathological changes and hydroxyproline (Hyp) content of hepatic tissue were detected.</p><p><b>RESULTS</b>(1) Typical chronic liver injury and fibrosis became evident in the model rat at the 8th week and cirrhosis came into being at the 12th week. (2) Compared with the rats in the model group, hepatic pathological changes were alleviated significantly, content of Hyp in hepatic tissue was decreased markedly and hepatic function improved remarkably in the XD group and YgD group. The improvement in the XD group was superior to that in the YgD group, while the serum albumin level elevated more significant in the YgD group.</p><p><b>CONCLUSION</b>The main pathological changes during CCl4 induced liver cirrhosis formation in rats is the rapid hyperplasia of hepatic fibrous connective tissue and obstruction of collaterals by blood stasis, thus induced reconstruction of the tissue structure, which could be treated with XD effectively, while the severe injury of liver parenchyma in this phase is another pathological change of Gan-yin deficiency syndrome, which could be effectively treated with YgD by its Yin-nourishing action.</p>

Proteomic analysis of proliferation and apoptosis in carbon tetrachloride induced rat liver fibrosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the proliferation and apoptosis in carbon tetrachloride induced rat liver fibrosis.</p><p><b>METHODS</b>Wistar rats were injected subcutaneously with 40% CCl4-olive oil twice weekly for 12 weeks. Liver tissues were obtained at the end of 4, 8, 12 and 16 weeks for histological examination, hydroxyproline (Hyp) assay and proteomic analysis. After two dimension electrophoresis (2-DE), the silver stained gels were analyzed with PDQUEST 2-DE. More than 30 differentially expressed proteins were identified by MALDI-TOF-MS.</p><p><b>RESULTS</b>The degree of collagen deposition and hydroxyproline content of the fibrotic livers increased continuously during the 12 weeks of CCl4 administration, peaked at the end of week 12 (P < 0.05) and declined significantly at week 16 (P < 0.05). Significant differences were observed in two parameters at each time point between the control and the model group. Meanwhile, dramatic change of hepatic proteome in the model group rats was also seen. Differentially expressed proteins identified by MALDI-TOF-MS were categorized as proliferation-related proteins/enzymes (proliferating cell nuclear antigen p120, p40 and cyclin F ubiquitin-conjugating enzyme 7 UBC7), and apoptosis-related proteins, mainly caspase-12 which was absent in the control rats.</p><p><b>CONCLUSION</b>Proliferation and apoptosis related proteins are expressed dynamically in different stages of rat liver fibrosis induced by CCl4.</p>