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Journal of Chinese Integrative Medicine ›› 2011, Vol. 9 ›› Issue (4): 423-434.doi: 10.3736/jcim20110412

• Original Experimental Research • Previous Articles     Next Articles

Effects of Chinese herbal medicine Yinchenhao Decoction on expressions of apoptosis-related genes in dimethylnitrosamine- or carbon tetrachloride-induced liver cirrhosis in rats

Ming-yu Sun1,2,3, Lei Wang1,2, Yong-ping Mu1,2, Cheng Liu1,2, Yan-qin Bian1,2, Xiao-ning Wang1,3, Ping Liu1,2,3()   

  1. 1. Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    2. Key Laboratory of Liver and Kidney Diseases (Ministry of Education) , Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    3. E-institute of Shanghai Municipal Education Commission, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2010-11-02 Accepted:2010-12-26 Online:2011-04-20 Published:2011-04-15
  • Contact: Liu Ping E-mail:liuliver@vip.sina.com

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Objective: To investigate the different efficacy of Yinchenhao Decoction (YCHD), a compound traditional Chinese herbal medicine, for liver cirrhosis induced by dimethylnitrosamine (DMN) or carbon tetrachloride (CCl4) in rats.
Methods: To induce liver fibrosis, 0.5% DMN solution (2 mL/kg body weight, i.p.) was given three consecutive days a week to male Wistar rats for 4 weeks. Cirrhotic rats were randomly divided into DMN group, YCHD group, Xiaochaihu decoction group by the end of the fourth week to accomplish a 2-week recipe treatment course. In CCl4-induced liver fibrosis model, 50% CCl4-olive solution was injected subcutaneously to rats at a dose of 2 mL/kg body weight twice a week to duplicate rat cirrhosis model. After 8 weeks, rats were divided into CCl4 group, CCl4 plus YCHD group and Xiaochaihu decoction group. For the YCHD group, YCHD was administered intragastrically once a day for 4 weeks. For DMN or CCl4 model, by the end of 6 or 12 weeks respectively, rats were sacrificed for sampling to detect liver function, hepatic histological changes, hydroxyproline (Hyp) content and apoptosis-related gene expressions.
Results: In DMN liver fibrosis model, hepatic fibrosis was obvious at week 2 and cirrhosis was evident at week 4 in DMN-treated rats. Compared to 6-week DMN group, hepatic pathological changes and liver function were improved significantly and content of Hyp decreased remarkably in YCHD group. In CCl4-induced liver fibrosis model, hepatic fibrosis was obvious at 8 weeks and cirrhosis was evident at 12 weeks in CCl4-treated rats. Compared to 12-week CCl4 group, hepatic pathological changes and liver function were not obviously improvement in YCHD group. The results of gene chip showed that YCHD significantly decreased Fas, Bax and caspase-3 gene expressions, and increased Bcl-xL gene expression in the liver of DMN model. However, in the model induced by CCl4 , YCHD did not inhibit hepatocyte apoptosis induced by CCl4 , but increased tyrosine kinase receptor gene expression by 4.8 times.
Conclusion: YCHD exerts more significant therapeutic effects on DMN-induced than CCl4-induced cirrhosis in rats in Hyp content and pathological change in liver tissue.

Key words: drugs, Chinese herbal, liver cirrhosis, dimethylnitrosamine, carbon tetrachloride, recipe-oriented syndrome, rats

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Figure 1

Histological changes of liver in rats with liver fibrosis induced by DMN observed by hematoxylin-eosin staining (Light microscopy, ×200) A: Normal group; B: Untreated group after 2-week modeling; C: Untreated group after 4-week modeling; D: Untreated group after 6-week modeling; E: Yinchenhao decoction group; F: Xiaochaihu decoction group."

Figure 2

Histological changes of liver in rats with liver fibrosis induced by carbon tetrachloride observed by hematoxylin-eosin staining (Light microscopy, ×200) A: Normal group; B: Untreated group after 4-week modeling; C: Untreated group after 8-week modeling; D: Untreated group after 12-week modeling; E: Yinchenhao decoction group; F: Xiaochaihu decoction group."

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Figure 3

Expressions of genes associated to cell apoptosis pathways in rats after 4-week modeling with CCl4 Expressions of Fas ligand downstream RGD:6191831 and mitochondrial apoptosis pathway activating factor Myc gene were significantly increased. Gene expressions of RGD:6191831 and Myc in the model were 4.53 and 2.6 times of that in the normal rats, respectively. Rats were injected with carbon tetrachloride and olive oil (1︰1, v/v) at a dose of 2 mL/kg body weight."

Figure 4

Expressions of genes associated to cell apoptosis pathways in rats after 8-week modeling with CCl4 Expressions of Fas ligand downstream RGD:6191831 and mitochondrial apoptosis pathway activating factor Myc gene were significantly increased. Gene expressions of RGD:6191831 and Myc in the model were 3.37 and 1.8 times of that in the normal rats, respectively. Rats were injected with carbon tetrachloride and olive oil (1︰1, v/v) at a dose of 2 mL/kg body weight."

Figure 5

Expressions of genes associated to cell apoptosis pathways in rats after 12-week modeling with CCl4 Expressions of Fas ligand downstream RGD:6191831 and mitochondrial apoptosis pathway activating factor Myc gene were significantly increased. Gene expressions of RGD:6191831 and Myc in the model were 4.48 and 3 times of that in the normal rats, respectively. NF-κB gene expression was 2.67 times of the normal group. Rats were injected with carbon tetrachloride and olive oil (1︰1, v/v) at a dose of 2 mL/kg body weight."

Figure 6

Effects of Yinchenhao decoction on genes associated to cell apoptosis pathways in CCl4 modeling rats (compared with normal rats)"

Figure 7

Expressions of genes associated to cell apoptosis pathways in rats after 2-week modeling with DMN Gene expressions of Irf-1, Fas and Bax in the model rats at 2 weeks were 2.24, 2.89 and 1.9 times of that in the normal rats, respectively. Rats were injected with dimethylnitrosamine (DMN) at a dose of 10 μL/kg body weight."

Figure 8

Expressions of genes associated to cell apoptosis pathways in rats after 4-week modeling with DMN Gene expression of Irf-1 was decreased. However, gene expressions of Fas and Bax further increased to 3.42 and 2.68 times of the normal, respectively. Rats were injected with dimethylnitrosamine (DMN) at a dose of 10 μL/kg body weight."

Figure 9

Expressions of genes associated to cell apoptosis pathways in rats after 6-week modeling with DMN Gene expressions of Irf-1 and Bax were down-regulated rapidly, while Fas gene expression was 2.04 times of the normal group."

Figure 10

Effects of Yinchenhao decoction on genes associated to cell apoptosis pathways in DMN modeling rats (compared with normal rats)"

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