Effect of recombinant human growth hormone and interferon gamma on hepatic collagen synthesis and proliferation of hepatic stellate cells in cirrhotic rats

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• 作者：Yong-Hua Chen ; Bing-Qing Du ; Zhen-Jiang Zheng ; Guang-Ming Xiang ; Xu-Bao Liu ; Gang Mai ; ^{maigang68@hotmail.com}
• 关键词：growth hormone ; interferon gamma ; hepatic stellate cell ; liver cirrhosis ; collagen
• 刊名：Hepatobiliary & Pancreatic Diseases International
• 出版年：2012
• 期刊代码：pca182_14993872
• 类别：med
• 出版时间：15 June, 2012
• 卷：11
• 期：3
• 页码：294-301
• 文件大小：365 K

摘要

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Background

Fibrosis plays a key role in the development of liver cirrhosis. In this study, we investigated the effect of growth hormone and interferon gamma on hepatic collagen synthesis and the proliferation of hepatic stellate cells in a cirrhotic rat model.

Methods

Cirrhosis was induced in rats using carbon tetrachloride. Rats were simultaneously treated with daily subcutaneous injections of recombinant human growth hormone or interferon gamma combined with recombinant human growth hormone. The control group was given saline. The relative content of type I and type IV collagen was assessed by indirect immunofluorescence analysis. Activated hepatic stellate cells were prepared from cirrhotic rats. The 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) method was used to assess the effects of recombinant human growth hormone and interferon gamma on these cells in vitro.

Results

Both qualitative and quantitative analysis showed that type I and type IV collagen secretion increased with time after recombinant human growth hormone administration and was significantly higher than control and recombinant human growth hormone combined with interferon gamma administration. In vitro, recombinant human growth hormone significantly stimulated hepatic stellate cell proliferation in a concentration-dependent manner (10^鈭?-10^鈭? mg/100 渭L,), and interferon gamma (10^鈭?-10^鈭? 渭g/100 渭L) significantly inhibited their growth compared to the control group. Interferon gamma combined with recombinant human growth hormone eliminated this growth-promoting effect to a certain degree in a concentration-dependent manner (10^鈭? 渭g/100 渭L, P<0.05, 10^鈭?-10^鈭? 渭g/100 渭L, P>0.05) and a time-dependent manner (P<0.05).

Conclusions

Recombinant human growth hormone increased collagen secretion in cirrhotic rats in vivo and promoted the proliferation of hepatic stellate cells from cirrhotic rats in vitro. It is possible that concurrent interferon gamma therapy can offset these side-effects of recombinant human growth hormone.