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Journal of Chinese Integrative Medicine ›› 2011, Vol. 9 ›› Issue (6): 651-657.doi: 10.3736/jcim20110612

• Original Experimental Research • Previous Articles     Next Articles

Effects of Chinese herbal medicine Yiguanjian Decoction on collagen metabolism of hepatic tissues in rats with CCI4-induced liver fibrosis

Xiao-ning Wang, Qing Tao, Qin Feng, Jing-hua Peng, Ping Liu, Yi-yang Hu()   

  1. Institute of Liver Diseases, Shuguang Hospital, E-institute of Traditional Chinese Internal Medicine of Shanghai Municipal Education Commission, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2011-03-25 Accepted:2011-04-11 Online:2011-06-20 Published:2011-06-15
  • Contact: Hu Yi-yang E-mail:yyhuliver@163.com

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Objective: To investigate the effects of Yiguanjian Decoction, a compound traditional Chinese herbal medicine, on collagen metabolism of hepatic tissues in rats with carbon tetrachloride (CCl4)-induced liver fibrosis.
Methods: Liver fibrosis was induced in rats by intraperitoneal injection of 50% CCl4-olive oil solution at a dose of 1 mL/kg body weight, twice per week for 9 consecutive weeks. Six rats were sacrificed for dynamic observation at the end of the 3rd and 6th week respectively, and the other rats were divided into 9-week untreated group and Yiguanjian Decoction group which was given Yiguanjian Decoction intragastrically in the subsequent 3-week modeling period. Another 6 rats were used as normal group. Rats in the normal group and 9-week untreated group were treated with distilled water. At the end of the 9th week, all rats were sacrificed, and their blood serum and liver tissue were collected for measuring hepatic histology and expressions of α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, matrix metalloproteinase (MMP)-13, MMP-14, collagen type Ⅰ (ColⅠ), and activities of MMP-2 and -9.
Results: Compared with the normal group, collagen fiber deposition, expressions of α-SMA, ColⅠ, TIMP-1, TIMP-2, MMP-13 and MMP-14 and activities of MMP-2 and -9 in the liver tissues gradually increased in the untreated group (P<0.05, P<0.01). These changes were significantly suppressed by Yiguanjian Decoction.
Conclusion: Yiguanjian Decoction exerts inhibition on formation of CCl4-induced cirrhosis in rats. The therapeutic mechanism may be related to inhibiting hepatic stellate cell activation, collagen secretion, and promoting collagen fiber degradation.

Key words: liver fibrosis, hepatic stellate cell, collagen metabolism, Yiguanjian Decoction, rats

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Figure 1

Expressions of α-SMA, TIMP-1, TIMP-2, MMP-13 and MMP-14 proteins in liver tissues of rats measured by Western blotting A: Expressions of α-SMA, TIMP-1, TIMP-2, MMP-13, MMP-14 and GAPDH proteins, which were consecutively blotted by incubation with different antibodies on the same membrane. 1: 9 week normal group; 2: 3 week untreated group; 3: 6 week untreated group; 4: 9 week untreated group; 5: Yiguanjian Decoction group. B, C, D, E,F: Semi-quantification results of α-SMA, TIMP-1, TIMP-2, MMP-13 and MMP-14 with GAPDH, represented as the mean±SD, n=3. ▲, P<0.05, ▲▲,P<0.01. MMP: matrix metalloproteinase; TIMP: tissue inhibitor of metalloproteinase; α-SMA: α-smooth muscle actin; GAPDH: glyceraldehyde-3-phosphate dehydrogenase."

Figure 2

Expression of collagen type Ⅰ in liver tissues of rats measured by immunofluorescent staining (Cy2, green) (Light microscopy, ×200) A: Normal group; B: 3 week untreated group; C: 6 week untreated group; D: 9 week untreated group; E: Yiguanjian Decoction group."

Figure 3

Changes of MMP-2 and MMP-9 activities in liver tissues of rats observed by Gelatin zymography A: Gelatin zymography of MMP-9 and MMP-2. 1: 9 week normal group; 2: 3 week untreated group; 3: 6 week untreated group; 4: 9 week untreated group; 5: Yiguanjian Decoction group. B, C: Semi-quantification results of MMP-9 and -2 activities, represented as the mean±SD, n=3. ▲, P<0.05, ▲▲, P<0.01. MMP: matrix metalloproteinase."

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