| The experiment through alcohol gavage method to establish the rats model of ethanol liver injury, to study the factors expression of silent information regulator1(SIRT1), tumor necrosis factor alpha (TNF-alpha) and nuclear factor-kappaB (NF-κB) in alcoholic liver injury rats, Investigate the effects of apoptosis on alcoholic liver injury rats, and the mechanism of cell factor in alcoholic liver injury, to investigate the relationship of occurrence and development between the apoptosis and alcoholic liver injury.72male Wistar rats (SPF) were randomly divided into6groups, the normal control group, the model control group, the high dose group of resveratrol(100mg/kg), middle dose group of resveratrol(50mg/kg), low dose group of resveratrol(25mg/kg) and positive drug control group.12rats in each group. The normal control group received normal saline by gavage, and the others were prepared ethanol (8mL/kg) administration by gavage. In resveratrol and positive drug groups, resveratrol was gavaged at the dose of25mg/kg,50mg/kg,100mg/kg and positive drug4g/kg in an hour after with ethanol administration. For30days, after the last dosing, the rats were fasted for12hours, weighed the quality, and all of the rats were sacrificed, the indexes of liver, kidney and spleen were determined. The level of serum aspartate aminotransferase(AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), triglyceride (TG), total cholesterol (TC), bilirubin (TB1L), low density lipoprotein cholesterol (LDL-c), gamma glutamyl transpeptidase (GGT), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined. With hematoxylin and eosin (HE) staining of liver, liver histopathological change and the degree of hyperplasia were observed. Detection of apoptotic cells in liver tissues (TUNEL), to observe the apoptosis. The expression content of SIRT1, TNF-alpha and NF-κB in the liver tissues were tested by immunohistochemistry method.Compared with the control group, The levels of ALT and AST in rats serum were significantly higher (P<0.05), the ratio of AST/ALT was two, the alcoholic liver injury model of rats were copied successfully.Compared with the control group, the liver index of the model group was significantly higher (P<0.01), and the renal index and spleen index were not statistically significant. Compared with the model group, high and middle dose group of resveratrol liver index decreased significantly, and the difference is significant (P<0.05), and kidney and spleen index, high, middle, low dose group of resveratrol and drug group of kidney and spleen index, no statistical significance (P>0.05).HE staining tissue sections under light microscope, compared with the normal control group, model control group hepatic cells showed obvious swelling, showed obvious hydropic degeneration, partial cells showed ballooning degeneration, hepatic lobules part had infiltration of inflammatory cells, liver tissue hyperplasia, occasional ranging from the size of fat droplets. Compared with the model control group, in the dose group of resveratrol and the drug group the mild swelling of the liver cells was significantly alleviated, and the degree of liver tissue degeneration was also significantly alleviated.Compared with the control group, the contents of GGT and LDH in rats serum were significantly higher (P<0.05), and the differences were significant. Compared with the model control group and three dosages of resveratrol can significantly decrease the levels of ALT and AST, including resveratrol high dose group and drug group can decrease the serum level of ALT contents (P<0.01), middle and low dose groups of resveratrol significantly reduced ALT levels (P<0.05); in each dose group of resveratrol significantly reduced the AST levels (P<0.05), the drug group significantly reduced the AST (P<0.01), was related to the measurement. Compared with the model group, resveratrol in each dosage group and drug group of LDH content decreased, but between the groups no dose related; high and middle dose group of resveratrol significantly reduces the GGT levels (P<0.05). the content of resveratrol in low dose group of GGT somewhat lower, but the difference was not significant, drug group significantly reduced the GGT content (P<0.01).The contents of TC, LDL-c, TG and TB1L in serum of rats were significantly higher than that in control group (P<0.01). Compared with the model group, resveratrol, low dose group and three drug groups could significantly decrease the level of TC in rats (P<0.05). the drug group can significantly reduce the content of TC (P<0.01); high dose group of resveratrol and drug group can significantly reduce the content of TG(P<0.05). in middle and low dose group of resveratrol could reduce the effect on the content of TG, but the difference was not statistically significant. Three dosage groups of resveratrol could significantly reduce the content of LDL-c (P<0.05), the drug group significantly reduced the content of LDL-c (P<0.01); high dose group of resveratrol and drug group decreased the content of TB1L significantly (P<0.01), in middle and low dose groups significantly reduced the content of TBIL (P<0.05).Compared with the blank control group. The content of SOD decreased and the content of MDA were increased (P<0.05) Compared with the model group, the contents of SOD were improved and the contents of MDA were reduced in resveratrol and drug groups (P<0.05), and have the statistically significant.Compared with the blank control group, hepatic cell apoptosis index was significantly increased. In model group, the expression of NF-κB and TNF-α were increased (P<0.05) in liver tissue, the expression of SIRTI was decreased significantly (P<0.05). Compared with the model group, Liver cell apoptosis index decreased significantly in high and middle dose group of resveratrol and drug group, there was significant difference (P<0.05). The expression of NF-κB and TNF-a were significantly decreased in each resveratrol groups and drug groups (P<0.05), the expression amount of SIRT1was significantly increased in resveratrol group (P<0.05).Resveratrol can reduce the liver injury induced by the alcohol, has protective effect on ethanol induced liver injury. The protective effect of resveratrol on alcoholic liver injury, have a connection with increasing the expression of SIRT1, inhibition of NF-κB and TNF-α. |
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