| Recently, due to the high fat, sugar, alcohol and hormone food intake increases, the nonalcoholic fatty liver disease incidence is increasing year by year with a lowering tendency of age. And it is also the important cause of liver cirrhosis and liver cancer. At the same time, NAFLD is a primary or secondary disease for animals, it not only causes a serious economic damage in livestock breeding, but also with the sick animals into the food, processed products and other flowing markets, causes directly or indirectly harm to human through the food chain.Thus NAFLD has become a global concern of social health issues and food safety issues. But now, there are less effective drugs, both at home or abroad, for the prevention and treatment of the disease.Previous studies shown NAFLD pathogenesis is connect with the cytochrome P450 (cytochrome p450, CYP450). CYP450 is the major phaseâ… metabolic enzymes in vivo, contains a number of isoenzymes and murine cytochrome P450 2A5 (CYP2A5) is an important member of CYP450, its activity effected by many factors, and different from other CYP450 enzymes show a unique up-regulation in the development and progression of the disease. Besides, murine CYP2A5 and human CYP2A6 enzymes are the same origin, each served in different species with similar functions, then have played a significant role in exogenous drugs and structure of different pre-carcinogen activation and the development of disease. Murine CYP2A5 is suitable as a model of human CYP2A6. As Food, environment or disease etc. will affect the expression of CYP2A5/CYP2A6, so the research on CYP2A5 can further understand the molecular mechanism of process and development of NAFLD, and in NAFLD case the effects of various pharmacological pathway and effective target site, provide a scientific basis for developing and researching new veterinary drug of prevention NAFLD, while for the prevention of human liver-related diseases and cancer, guiding human clinical rational use is significance. However, until now, researches on whether NAFLD have an effect on the expression of CYP2A5 and whether NAFLD and drugs have synergistic effect on the CYP2A5 have not been reported yet.This study will use artificially induced NAFLD C57BL/6J mice as experimental animals to reseash NAFLD have effect on the expression of CYP2A5 and discuss the interaction among drugs, NAFLD and CYP2A5 and the changes of CYP2A5 induce by drugs and NAFLD, these reveal liver injury causing by NAFLD and interaction with pyrazole, phenobarbital, its gene expression. The results showed:1. With the induction of pyrazole, phenobarbital, CYP2A5 protein level, enzyme activity and CYP2A5 mRNA in C57BL/6 mice liver increase compared with the control group(P<0.01). It means that drugs increased the expression of CYP2A52. With the induction of NAFLD, CYP2A5 protein level, enzyme activity and CYP2A5 mRNA of C57BL/6 mouse liver also increase compared with the control group(P<0.01). It means that NAFLD showed up-regulation on the expression of CYP2A5.3. With the joint induction of drugs and NAFLD, CYP2A5 protein level, enzyme activity and CYP2A5 mRNA of C57BL/6 mouse liver also increase compared with the control group. And it is more conspicuous (P<0.01)than the other two groups. It means that they have a synergistic effect with each other in the induction progress.My research primarily found that NAFLD shows up-regulation on the CYP2A5 of C57BL/6 mouse liver. At the same time, it has synergistic effect with Pyrazole and Phenobarbital on increasing the expression of CYP2A5. All these may lay a foundation for the further study on molecular mechanism of CYP2A5 in NAFLD.
|
PDF Full Text Request