The Role Of CPTIα In The Alcoholic Fatty Liver Disease

Objective:Alcoholic liver disease(alcoholic liver disease. ALD) is a liver disease caused by long-term heavy drinking. Alcoholic fatty liver disease(AFLD) is the earliest pathological change of liver when exposed to ethanol, and then can lead to steatohepatitis, hepatic fibrosis, eventually leading to cirrhosis. Wide-ranging necrosis of hepatocellular even acute liver failure can be made by heavy drinking in short time. Epidemiological survey found that ALD accounted for the proportion of patients with liver disease showed an upward trend year by year, in our country. The problem that the toxic of alcohol to hepatocellular can’ot allow to be ignored. Liver is the core organs of alcohol metabolism and lipid metabolism balance. Alcohol metabolism destruct lipid metabolic balance, and then hepatic fatty acid oxidation reduce, synthesis increase, that lead to excessive lipid deposition in hepatocytes, and cause lipid toxic effects. carnitine palmitoyltransferase I(CPTI) located on the outer mitochondrial membrane, a key enzyme in controlling fatty acid β oxidation. Some experiments have revealed that the expression and activation of CPTI could be affected through Adiponectin, adenosine monophosphate activated protein kinase(AMPK),Silent Information Regulator1(SIRT1), peroxisome proliferator-activated receptorα(PPARα) and Sterol regulatory element binding proteins(SREBP). Our previous studies have shown that the levels of AMPK, SIRT1, Adiponectin were gradually reduced throughout the procession of ALD. Although the progression of ALD is well-characterized, there is no universally accepted therapy available to halt or reverse this process in humans except abstinence. In the present study, our purpose is to examine the protective role of CPTI and it’s change in a rats model of binge ethanol, rational targeted therapy may be developed to treat or prevent ALD.Methods: Male Wistar rats were selected as experimental subject, Rats model for ALD were established by intragastric ethanol. Liver samples obtained at 0W, 4W, 8W, 12 W and 16 w respectively through rats sacrificed randomly. Histopathological examinations were used to show the expression of CPTIα in hepatic tissue. Real Time-quantitative Polymerase Chain Reaction(RT-q PCR)CPTIα were used to examine the m RNA changes of CPTIαand Western blotting was performed to examine the protein level of CPTIα.Results:1 Histopathological examinations showed that, the expression of CPTIα was gradually reduced as the consumption of alcohol. Fatty deposition in hepatocellular gradually increased.2 The gene and protein levels of CPTIα were gradually decreased throughout the progress of ALD.3 The m RNA level of CPTIα were gradually down-regulated both in 4W, 8W, 12 W and 16 W, along with the stimulation of alcohol. compared with 0W, the level of CPTIα showed a decrease at 4W(2.10±0.72 VS 1.80±0.63, P<0.01). the level of CPTIα at 12 W were less than 8W(1.72±0.65 VS 1.13±0.68,P<0.05). Meanwhile, with the prolonging of stimulation, the m RNA level of CPTIα were more significant down-regulated at 16 W than 8W(1.72±0.65 VS 0.83±0.67,P <0.01).4 The protein expression of CPTIα were gradually down-regulated both in 4W,8W,12 W and 16 W, along with the stimulation of alcohol. compared with 0W, the protein expression of CPTIα showed a decrease at 4W(1.16±0.08 VS 0.94±0.06, P<0.01). the protein expression of CPTIα at 12 W were less than 8W(0.78±0.06 VS 0.69±0.07,P<0.05). Meanwhile, with the prolonging of stimulation, the protein expression of CPTIα were more significant down-regulated at 16 W than 8W(0.78±0.06 VS 0.38±0.02,P <0.01).Conclusions:1 Diet containing alcohol could induce alcohol liver disease as modeling.2 The protein and m RNA expression level of CPTIα were gradually decreased throughout the progress of ALD.