Effects Of Ethanol On Peripharal Circadian Clcok And Physiological Functions In Rats

With the acceleration of the process of economic globalization,a variety of commercial exchanges increase rapidly,and the consumption of ethanol is also growing.Various diseases and social problems caused by ethanol in China even around the world are becoming more serious.Thus,researches on ethanol are carrying out worldwidely.However,most previous studies have concerned on the role of ethanol,as a single factor,in affecting circadian clock regulation,lipid metabolism and other aspects.Little is concerning on the interaction among biological clock,ethanol and physiological functions.In the present study,using male Wistar rat as an animal model,we investigated the impact of chronic and acute ethanol on peripheral circadian clock and physiological functions,and then explored the role of liver autonomous clock in the effect of ethanol on regulating physiologic functions.Our results showed that the acute ethanol significantly changed the expression of the peripheral circadian clock genes,and key lipid metabolism genes,Gotl and Pai1 in the liver.While the ethanol stimulated at different time of a day(CTO and CT12),its effect was also different.Ethanol stimuli at CTO not only strongly affected the expression of Perl in the heart,liver and kidney,but also significantly altered the expression of the key genes associated with lipid metabolism,as compared with those respective ones at CT12.However,the expression of Pai1 was more easily affected by ethanol injected at CT12.These results suggested that the ethanol consumption at the time of CT12 might cause hepatic fibrosis easily.Results obtained from one-day reversed-feeding(RF)experiment showed that the responses of the hepatic clock genes to the acute ethanol at various time points in this experimental condition exhibited almost completely opposite patterns as compared to the those in the normal acute-ethanol experiment as described above.Thus,the liver autonomous circadian clock might be involved in regulating the liver physiological functions.Results obtained from the chronic-ethanol experiment showed that the expression of the genes related to the key lipid metabolism,such as Gpt,Got1,Crp and Pai1,displayed an obvious 24h-biorhythm under normal circumstances.As a kind of food ingredient,a long-term consumption of ethanol indeed had a clear role in regulating peripheral circadian clock genes,especially Decl and Perl.Chronic ethanol consumption significantly altered the rhythmic expression patterns of physiological function genes,suggesting that various types of chronic liver disease caused by ethanol might be mediated through the circadian clock pathway.Acute ethanol also could significantly change the expression of the peripheral circadian clock genes,liver key lipid metabolism genes,Gotl,Crp and Pai1 in alcoholism rats.However,in the situation of the alcoholism rats,the responsive sensitivity of the heart and liver clock genes to the acute ethanol was significantly reduced,while the effect of the acute ethanol on the expression of Got1,Crp and Pai1 was significantly enhanced,when compared with that of the simple acute ethanol stimulation.In conclusion,both acute ethanol and chronic ethanol stumili could significantly affect peripheral circadian clock.The effect of Ethanol on hepatic physiological function might be mediated via affecting the hepatic autonomous clock.All these results will provide further theoretical basis on selecting of drinking time and the chronotherapy of hangover drug.