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World J Gastroenterol. May 14, 2008; 14(18): 2905-2911
Published online May 14, 2008. doi: 10.3748/wjg.14.2905
Rosiglitazone prevents murine hepatic fibrosis induced by Schistosoma japonicum
Hui Chen, Yong-Wen He, Wen-Qi Liu, Jing-Hui Zhang
Hui Chen, Yong-Wen He, Department of Infectious Disease, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Wen-Qi Liu, Department of Parasitology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Jing-Hui Zhang, Department of Surgical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China
Author contributions: Chen H contributed chiefly to this work; Chen H designed and performed the research and wrote the paper; Chen H, Liu WQ and Zhang JH performed the research; He YW gave some good suggestions.
Correspondence to: Hui Chen, Department of Infectious Disease, Union Hospital, Tongji Medical college, Huazhong University of Science and Technology, 1277# Jiefang Road, Wuhan 430022, Hubei Province, China. chenhui0515@yahoo.com.cn
Telephone: +86-27-85726132
Fax: +86-27-85727851
Received: January 25, 2008
Revised: March 8, 2008
Published online: May 14, 2008
Abstract

AIM: To evaluate the effect of rosiglitazone in a murine model of liver fibrosis induced by Schistosoma japonicum infection.

METHODS: A total of 50 mice were randomly and averagely divided into groups A, B, C, D and E. The mice in group A served as normal controls, while those in the other four groups were infected with Schistosoma japonicum to induce the model of liver fibrosis. Besides, the mice in groups C, D and E were treated with praziquantel, rosiglitazone and praziquantel plus rosiglitazone, respectively. NF-κB binding activity and expression of PPARγ-mRNA were determined by Western blot assay and real-time quantitative PCR. Radioimmunoassay technique was used to detect the serum content changes of TNF-α and IL-6. Histological specimens were stained with HE. Expression of TGF-β1, a-smooth muscle actin and type I and type III collagen was detected by immunohistochemistry and multimedia color pathographic analysis system.

RESULTS: Inflammation and fibrosis in the rosiglitazone plus praziquantel treatment group (group E) were lightest among the mice infected with Schistosoma (P < 0.05). To further explore the mechanism of rosiglitazone action, we found that rosiglitazone can significantly increase the expression of PPARγ [E: -18.212 ± (-3.909) vs B: -27.315 ± (-6.348) and C: -25.647 ± (-5.694), P < 0.05], reduce the NF-κB binding activity (E: 88.89 ± 19.34 vs B: 141.11 ± 15.37, C: 112.89 ± 20.17 and D: 108.89 ± 20.47, P < 0.05), and lower the serum level of TNF-α (E: 1.613 ± 0.420 ng/mL vs B: 2.892 ± 0.587 ng/mL, C: 2.346 ± 0.371 ng/mL and D: 2.160 ± 0.395 ng/mL, P < 0.05) and IL-6 (E: 0.106 ± 0.021 ng/mL vs B: 0.140 ± 0.031 ng/mL and C: 0.137 ± 0.027 ng/mL, P < 0.05) in mice with liver fibrosis. Rosiglitazone can also substantially reduce the hepatic expression of TGF-β1, α-SMA type I and type III collagen in mice with liver fibrosis.

CONCLUSION: The activation of PPARγ by its ligand can retard liver fibrosis and suggest the use of rosiglitazone for the treatment of liver fibrosis due to Schistosoma japonicum infection.

Keywords: Peroxisome proliferators-activated receptorγ, Rosiglitazone, Liver fibrosis, Schistosomiasis, Hepatic stellate cell