Study on the platform development for therapeutics of liver disease involving liver immunobiology

• Main Authors: Yuan-Chi Huang, 黃元麒
• Other Authors: Rong-Tsun Wu
• Format: Others
• Language: zh-TW
• Online Access: http://ndltd.ncl.edu.tw/handle/56947723828479903610

碩士 === 國立陽明大學 === 生物藥學研究所 === 97 === The liver maintains in a special condition, called “tolerance”. The pathology and physiology of the liver are dependent on balance between tolerance and immunity. There are many liver diseases involving in lipopolysaccharides (LPS). The liver is the major site of LPS clearance. In addition, the autophagy is involving in clearance and protection liver form oxidative stress. In this study, a drug-screening platform for anti-inflammation and autophagy inducer in liver is developed. First, the primary hepatocytes and cell lines are treated with LPS. Then the liver slices which maintain the correct architectural relationship of all cells present are applyed. In the present study, the extract of Taraxacum mongolicum and Cocos nucifera can reduce the LPS-induced inflammation significantly. The effects of Cocos nucifera on the acute liver inflammation in mice induced by LPS/D-galactosamine (D-GalN) are then investigated. The results showed that Cocos nucifera protect against LPS/D-GalN-induced liver injury, including decrease of ALT/AST release and the expression of TNF-α. In addition, MDC staining of hepatocytes are used for screening drugs that increase autophagy. Arctium lappa increased tendency for MDC staining, suggesting increased lysosomal and/or autophagy activity. The conversion of LC3-I to LC3-II is significantly increased, confirming the effect on inducing autophagy. In addition, the expression of bFGF is high in LPS/D-GalN-induced inflammation and in LPS-treated hepatocytes. Thalidomide has the property for reducing this inflammation. In the previous study, thalidomide (at 0.1 μg/ml) can reduce cellular bFGF levels and affect tumor anchorage-independent growth. Whether the immunomodulatory effect of thalidomide is also through decreasing bFGF pathway? In the study, the bFGF can increase the LPS-induce inflammation. When neutralizing antibodies are used to block bFGF pathway, the expression of TNF-α and production of NO are reduced. In conclusion, the extract of Taraxacum mongolicum and Cocos nucifera can reduce LPS-induced liver inflammation. Furthermore, bFGF may play a role in inflammation.