| Backgrounds and Purposes:Alcoholic liver disease (ALD) is one kind of toxic liver diseases resulted from overdose of ethanol intake. Long-term consumption of alcohol results in spectrum of the liver abnormalities, ranging from simple fatty liver (steatosis) to steatohepatitis, cirrhosis and hepatocellular carcinoma. Recently, along with the increasing alcohol wastage, the incidence of ALD is increasing too.Alcohol has strong cytotoxic effect, especially on the liver. Recently it was found that hepatocyte apoptosis played an important role in procession of ALD, but the exact mechanisms of apoptosis in ALD still remain unclear. There is powerful potential in regeneration of the liver. The abnormality of the liver regeneration is closely relevant to the disorders of hepatic function, hepatitis, cirrhosis and hepatocellular carcinoma. Steatosis, necrosis and regeneration take place in hepatocytes repeatedly during long-term alcohol intake, which may finally lead to fibrosis and cirrhosis. Many reports announced that alcohol might inhibit the hepatocyte proliferation, but a few reports proclaimed that as hepatocyte apoptosis in ALD increased, hepatocyte proliferation also increased.There is equilibrium between hepatocyte apoptosis and proliferation but few reports have ever covered it. It may contribute to the prevention and treatment of ALD to make the equilibrium clear.Nuclear factor kappa B (NF B) is an important transcription regulator in apoptosis and proliferation. NF B can be activated by many stimulus and then switch on the transcription of the aim genes, and play a crucial role in inflammation, immune, apoptosis and so on. Cyclooxygenase-2 (COX-2) is one of the aim genes of NF B. COX-2 participates in hepatic metabolism disorder, inflammation and fibrosis in ALD. Many reports have revealed that the activation of NFicB may correlate to the expression of COX-2 in silicosis, vascular endothelial injury, oxidative stress and kinds of inflammation, but COX-2 expression in rat vascular smooth muscle cells is unrelated to NF B activation. However the role of COX-2 expression in hepatocyte apoptosis in ALD and its relationship to NF B activation has not been elucidated yet.The present study aims to demonstrate hepatocyte apoptosis and proliferation in rats after long-term alcohol intake, to observe the expression of NF B and COX-2, so to reveal their roles and relationship in the mechanisms of ALD.Materials and Methods:Twenty-four healthy Sprague-Dawley rats, weighing between 180 and 210 (196 12) grams, were divided randomizedly into two groups, alcohol group and control group. After the rats were generally feeded for one week, alcohol (56%, 15ml/kg) or normal saline of the same volume were given daily to the rats in the alcohol or control group separately. The rats were killed at the end of the 24th week and the samples of the livers were taken immediately to be fixed in 10% formaldehyde solution, embedded in paraffin and then made into sections in 5 m thick.HE staining was carried out to observe the basic pathology change of the liver. Hepatocyte apoptosis was detected with the method of terminal-deoxynucleotidyl transferase mediated d-UTP nick end labeling (TUNEL) and the hepatocyte proliferation was measured by the expression of proliferative cellular nuclear antigen (PCNA) with the method of immunohistochemistry (Envision). NF B and COX-2 were also tested with the method of immunohistochemistry.All the data were expressed in mean SD. Data analysis was performed by t-test, Chi-square test (Fisher exact test of probability) and Spearman linear correlation analysis, and the strength of the relationship is reported as r2. The acceptable level of significance (P) was less than 0.05. The statistic precessions were carried out in SPSS 10.0 for windows.Results:1. The general state of the rats: The rats in the control group were luster, active and appetitive. In contrast, the rats in the alcohol group were lusterless, sleepy, irritable, anepithymia, marasmus and...
|
PDF Full Text Request