AIM： To investigate if iron deposition and fat accumulation in the liver play a pathogenetic role in dimethylnitrosamine （DMN）-induced liver fibrosis in rat.METHODS： Thirty rats were treated with DMN at does conse...AIM： To investigate if iron deposition and fat accumulation in the liver play a pathogenetic role in dimethylnitrosamine （DMN）-induced liver fibrosis in rat.METHODS： Thirty rats were treated with DMN at does consecutive days of 10 μL/kg daily, i.p., for 3 consecutive day each week for 4 wk. Rats （n = 30） were sacrificed on the first day （model group A） and 21st d （model group B） after cessation of DMN injection. The control group （n = 10） received an equivalent amount of saline. Liver tissues were stained with hematoxylin ＆ eosin （HE） and Masson and Prussian blue assay and oberserved under electron microscopy. Serum alanine aminotransferase （ALT）and liver tissue hydroxyproline （Hyp） content were tested.RESULTS： The liver fibrosis did not automaticallyreverse, which was similar to previous reports, the perilobular deposition of iron accompanied with collagen showed marked characteristics at both the first and 21st d after cessation of DMN injection. However, fat accumulation in hepatocytes occurred only at the 21^st d after cessation of DMN injection.CONCLUSION： Iron deposition and fat accumulation may play important roles in pathological changes in DMN-induced rat liver fibrosis. The detailed mechanisms of these characteristics need further research.展开更多
AIM： To evaluate the therapeutic effect of Chunggan extract （CGX）, a modified traditional Chinese hepatotherapeutic herbal, on the dimethylnitrosamine （DMN）-induced chronic liver injury model in rats. METHODS： L...AIM： To evaluate the therapeutic effect of Chunggan extract （CGX）, a modified traditional Chinese hepatotherapeutic herbal, on the dimethylnitrosamine （DMN）-induced chronic liver injury model in rats. METHODS： Liver injuries were induced in Wistar rats by injection of DMN （ip, 10 mg/mL per kg） for 3 consecutive days per week for 4 wk. The rats were administered with CGX Coo, 100 or 200 mg/kg per day） or distilled water as a control daily for 4 wk starting from the 15^th d of the DMN treatment. Biochemical parameters （serum albumin, bilirubin, ALP, AST and ALT）, lipid peroxides, hydroxyproline, as well as histological changes in liver tissues were analyzed. In addition, gene expression of TNF-α, TGF-β, TIMP-1, TIMP-2, PDGF-β, and MMP-2, all of which are known to be associated with liver fibrosis, were analyzed using real-time PCR. RESULTS： CGX administration restored the spleen weight to normal alter having been increased by DMN treatment. Biochemical analysis of the serum demonstrated that CGX significantly decreased the serum level of ALP （P 〈 0.05）, ALT （P 〈 0.02）, and AST （P 〈 0.02） that had been elevated by DMN treatment. CGX administration moderately lowered lipid peroxide production and markedly lowered hydroxyproline generation caused by DMN treatment in accordance with histopathological examination. DMN treatment induced a highly upregulated expression of TNF-α, TGF-β,TIMP-1, TIMP-2, PDGF-β, and MMP-2. Of these, the gene expression encoding PDGF-β and MMP-2 was still further enhanced 2 wk after secession of the 4-wk DMN treatment, and was remarkably ameliorated by CGX administration. CONCLUSION： CGX exhibits hepatotherapeutic properties against chronic hepatocellular destruction and consequential liver fibrosis.展开更多
Objective:To observe the expression level of TNF-α mRNA in rats with hepatic fibrosis induced by dimethylnitrosamine (DMN) and to explore its relationship with collagen metabolism and its diagnostic value for hepatic...Objective:To observe the expression level of TNF-α mRNA in rats with hepatic fibrosis induced by dimethylnitrosamine (DMN) and to explore its relationship with collagen metabolism and its diagnostic value for hepatic fibrosis.Methods: Twenty-five male Wistar rats were randomly divided into normal control group (n=10) and model group (n=15). Model rats were induced by DMN for 4 weeks and at final stage were executed. TNF-α mRNA were detected by RT-PCR and the inflammatory necrosis and collagen deposition in hepatic tissue were observed by HE stain and Sirius red stain. The liver functions were determined by automatic biochemical analytic device. The serum marks of liver fibrosis, such as HA, LN and Ⅳ-C were measured with ELISA and RIA. Results: In this study, the rat model of liver fibrosis induced by DMN was successfully constructed. RT-PCR reveals that TNF-α mRNA expression in control group is lower than that of model group. The liver functions of model group were impaired compared with those of the control group (P<0.01). Semi-quantitive analysis revealed that TNF-α/β-actin of normal rats was 0.39±0.12, while 0.93±0.05 of model rats. The concentration of HA (434.44±98.81 vs 252.9±26.59 ng/ml, P<0.01), LN (70.67±6.32 vs 37.90±5.97 ng/ml, P<0.01) and Ⅳ-C (79.39±10.52 vs 21.40±4.17 ng/ml, P<0.01) were significantly increased in the model group as well. Changes of the indexes were similar to the pathological damage of the liver. Conclusion: The results suggested that activation of TNF-α in liver tissues may be the common pathogenic mechanism of liver fibrosis. TNF-α may be a useful index for the diagnosis of hepatic fibrosis which worthies further investigation.展开更多
文摘AIM： To investigate if iron deposition and fat accumulation in the liver play a pathogenetic role in dimethylnitrosamine （DMN）-induced liver fibrosis in rat.METHODS： Thirty rats were treated with DMN at does consecutive days of 10 μL/kg daily, i.p., for 3 consecutive day each week for 4 wk. Rats （n = 30） were sacrificed on the first day （model group A） and 21st d （model group B） after cessation of DMN injection. The control group （n = 10） received an equivalent amount of saline. Liver tissues were stained with hematoxylin ＆ eosin （HE） and Masson and Prussian blue assay and oberserved under electron microscopy. Serum alanine aminotransferase （ALT）and liver tissue hydroxyproline （Hyp） content were tested.RESULTS： The liver fibrosis did not automaticallyreverse, which was similar to previous reports, the perilobular deposition of iron accompanied with collagen showed marked characteristics at both the first and 21st d after cessation of DMN injection. However, fat accumulation in hepatocytes occurred only at the 21^st d after cessation of DMN injection.CONCLUSION： Iron deposition and fat accumulation may play important roles in pathological changes in DMN-induced rat liver fibrosis. The detailed mechanisms of these characteristics need further research.
基金Supported by the Oriental Medicine R and D Project, Ministry of Health and Welfare, Republic of Korea, No. B050018
文摘AIM： To evaluate the therapeutic effect of Chunggan extract （CGX）, a modified traditional Chinese hepatotherapeutic herbal, on the dimethylnitrosamine （DMN）-induced chronic liver injury model in rats. METHODS： Liver injuries were induced in Wistar rats by injection of DMN （ip, 10 mg/mL per kg） for 3 consecutive days per week for 4 wk. The rats were administered with CGX Coo, 100 or 200 mg/kg per day） or distilled water as a control daily for 4 wk starting from the 15^th d of the DMN treatment. Biochemical parameters （serum albumin, bilirubin, ALP, AST and ALT）, lipid peroxides, hydroxyproline, as well as histological changes in liver tissues were analyzed. In addition, gene expression of TNF-α, TGF-β, TIMP-1, TIMP-2, PDGF-β, and MMP-2, all of which are known to be associated with liver fibrosis, were analyzed using real-time PCR. RESULTS： CGX administration restored the spleen weight to normal alter having been increased by DMN treatment. Biochemical analysis of the serum demonstrated that CGX significantly decreased the serum level of ALP （P 〈 0.05）, ALT （P 〈 0.02）, and AST （P 〈 0.02） that had been elevated by DMN treatment. CGX administration moderately lowered lipid peroxide production and markedly lowered hydroxyproline generation caused by DMN treatment in accordance with histopathological examination. DMN treatment induced a highly upregulated expression of TNF-α, TGF-β,TIMP-1, TIMP-2, PDGF-β, and MMP-2. Of these, the gene expression encoding PDGF-β and MMP-2 was still further enhanced 2 wk after secession of the 4-wk DMN treatment, and was remarkably ameliorated by CGX administration. CONCLUSION： CGX exhibits hepatotherapeutic properties against chronic hepatocellular destruction and consequential liver fibrosis.
文摘Objective:To observe the expression level of TNF-α mRNA in rats with hepatic fibrosis induced by dimethylnitrosamine (DMN) and to explore its relationship with collagen metabolism and its diagnostic value for hepatic fibrosis.Methods: Twenty-five male Wistar rats were randomly divided into normal control group (n=10) and model group (n=15). Model rats were induced by DMN for 4 weeks and at final stage were executed. TNF-α mRNA were detected by RT-PCR and the inflammatory necrosis and collagen deposition in hepatic tissue were observed by HE stain and Sirius red stain. The liver functions were determined by automatic biochemical analytic device. The serum marks of liver fibrosis, such as HA, LN and Ⅳ-C were measured with ELISA and RIA. Results: In this study, the rat model of liver fibrosis induced by DMN was successfully constructed. RT-PCR reveals that TNF-α mRNA expression in control group is lower than that of model group. The liver functions of model group were impaired compared with those of the control group (P<0.01). Semi-quantitive analysis revealed that TNF-α/β-actin of normal rats was 0.39±0.12, while 0.93±0.05 of model rats. The concentration of HA (434.44±98.81 vs 252.9±26.59 ng/ml, P<0.01), LN (70.67±6.32 vs 37.90±5.97 ng/ml, P<0.01) and Ⅳ-C (79.39±10.52 vs 21.40±4.17 ng/ml, P<0.01) were significantly increased in the model group as well. Changes of the indexes were similar to the pathological damage of the liver. Conclusion: The results suggested that activation of TNF-α in liver tissues may be the common pathogenic mechanism of liver fibrosis. TNF-α may be a useful index for the diagnosis of hepatic fibrosis which worthies further investigation.
