| BackgroundExcessive drinking, chronic alcoholism has been the world's most serious public health problem. Alcoholic liver disease (Alcoholic Liver Disease, ALD), the most common and serious complication, is due to large quantities of alcohol-induced liver damage, which are series of diseases. ALD is ten common causes of death in Western countries, and also one of the most important reason and lead to cirrhosis. In recent years, as China's economic development and people's living standards improved, the alcohol-induced liver injury incidence increased year by year, has become the second largest serious problem except the viral liver disease, It has been a serious threat to public health, also the urgent medical issues need to study and solve.Clinical research found that, alcoholic liver disease is a progressive development of irreversible pathological changes, but there is no cure for clinical. So study the prevention and early treatment of liver injury and effective methods has an important Clinical and social value to reducing the incidence of alcoholic liver disease.The pathogenesis of alcoholic liver disease suggested that the key mechanisms is that,alcohol and its metabolites on the liver toxicity, and metabolism of oxygen free radicals, depletion of antioxidants GSH, lipid peroxidation and activation of several cytokines produced alcoholic liver injury and fibrosis.and propose to oxidative stress and lipid peroxidation in the center of the "two hits" hypothesis. However, free radicals for the pathogenesis of alcoholic liver disease, using natural plant extract's antioxidant intervention of alcohol on the liver injury prevention is rarely reported.Garlic which are daisy fructan carbohydrates is a polysaccharide extracted from garlic active compounds, domestic research confirmed that garlic polysaccharides have anti-oxidation, anti-virus, mediate lipid, blood sugar, enhance immunity, viral myocarditis, improve liver injury caused by CCL4.GP is very promising with the development of drugs or liver disease prevention and control of health food, but animal and human intervention in chronic alcoholic liver damage effects have rarely been studied.ObjectiveTo establish the model of chronic alcoholic liver injury in mice;To Observed the protection effect of Garlic Polysaccharide(GP) on alcoholic liver injury in mice,and to find out its mechanism in the context of antioxidant.To provide scientific basis on the prevention and early treatment of chronic alcoholic liver disease;Methods70 KM mice were randomly divided into 5 groups(14/group) according to weight and gender: control group, model group, GP groups(low:100mg/kg/d middle: 150mg/kg/d high:200mg/kg/d), mice in control group were fed with distilled water, other groups mice, with increasing dosage, were fed with 56°Beijing Red Star Erguotou from 0.05mL/10g.d dose,increasing to 0.12mL/10g.d dose the day before the end of the experiment, The last day fed with the impact of dose of 0.14mL/10g.d. 30min before alcohol toxicity, mice in control group and model group were fed with distilled water, other groups mice were fed with Garlic Polysaccharides of different doses. After 8 weeks of treatment of GP, all animals were killed and blood samples were taken to measure the activity of ALT,AST,and livers were taken to detect the activity of SOD,GSH-Px,GSH,MDA,ADH,ATP, and also fixed a liver biopsy.Result:1. General condition of mice with chronic alcoholismFrom 3 weeks of experiment Model group started to drooling after drink, scratching movements increased, and then present rigid body, slow, low in spirits and other symptoms, usually after 2 to 3 hours restore to normal. During 6 to 7 weeks, after drinking staggering gait, drowsiness and other obvious symptoms of chronic alcoholism became more significant, usually after 4 to 6 hours restore to normal.Compared with normal group, model group is poor appetite, weight gain, poor coat luster. Compared with model group, all groups of interfere with garlic polysaccharide drunk symptoms are relatively mild, sober up a relatively short time, an average of 2 to 3 hours, appetite, and relatively superficial gloss better than the model group. The results show that the polysaccharide of garlic can improve symptoms of chronic alcoholism.2. The Changes in body weight and the liver weight indexBody weight in each experimental showed a gradual upward trend during 1 to 3 weeks, the 4th week began to decrease, the 5th week, weight rebounded slightly higher, after 6th week body weight continued to decrease significantly, final weight lower than normal group (P<0.05), that indicate long-term excessive alcohol consumption affected mice's appetite, resulting in malnutrition. Compared with model group, middle and high of GP group body weight stable after the 5th week, no significant decrease, the final weight was significantly higher than the model group (P <0.05), low of GP group body weight although volatile, but compared with the model group, weight loss is not significant, results suggest that GP can improve mice's appetite. Compared with normal group, model group liver weight index was significantly higher (P<0.05), while the garlic polysaccharide in each experimental group liver weight index was significantly lower than model group (P<0.05), the results suggest that garlic polysaccharide on alcoholic liver injury have some protective effect.3. The activity of Serum AST,ALT levels and liver enzymesCompared with normal group,the activity of Serum AST,ALT levels of model group increased significantly (P<0.05), the activity of liver ATP enzyme decreased (P<0.05), the activity of ADH enzyme increased, indicating that long-term alcohol consumption has a serious liver injury in mice, the model of chronic alcoholism liver injury in mice succeeded; long-term excessive alcohol consumption can induce the expression of ADH enzyme, acetaldehyde formation aggravated liver damage. Compared with model group, the activity of serum ALT and AST of GP group were significantly lower (P<0.05), the activity of liver ADH enzyme decreased, the activity of liver ATP enzyme activities increased (P<0.05), confirmed that GP chronic has a protective effect on alcoholism liver injury mice, it can improve the activity of ATP enzyme, inhibited the high expression of ADH enzyme, reduced acetaldehyde production, to protect the liver. 4. The level of oxidation and antioxidantCompared with normal group, model group content of MDA were significantly higher, the content of GSH decreased significantly (P<0.05), the activity of SOD and GSH-Px antioxidant enzyme decreased significantly (P<0.05), show that liver damage in chronic alcoholism was related by oxidative and antioxidant imbalance. Compared with model group, the content of MDA of GP high dose group was significantly lower (P<0.05), and the middle dose group was the best, but the low dose group decreased was not significant (P>0.05); the content of GSH in each dose group increased significantly (P<0.05), the activity of SOD and GSH-Px antioxidant enzyme were significantly increased (P>0.05),showed a dose-response relationship. The results show that the protective effects of Garlic Polysaccharide on chronic alcoholism liver injury in mice was related to its increased antioxidant capacity5. Liver histologyLight microscopy of liver biopsy showed normal group hepatic lobules clear, Liver mononuclear cells were multilayered, cells arranged regularly, no degeneration and necrosis,no expansion of sinusoidal congestion, portal area no inflammatory cell infiltration; model group liver cells showed swelling, some region of the ballooning degeneration; lobular blurred, hepatocellular microvesicular steatosis, and occasionally guns steatosis, portal area with inflammatory cell infiltration, lobular necrosis increased significantly,indicated that alcohol administered for 8 weeks has caused liver damage in mice, rendering fat and inflammatory pathology, confirmed that chronic alcoholism liver injury model established successfully. Compared with model group, GP groups reduced swelling of liver cells, liver cells in a small number of mild edema, hepatic lobule and portal area was no inflammatory cell infiltration, improved significantly. Show that the reversal of garlic polysaccharide fatty degeneration of liver cells and reduce inflammation and repair liver cells.ConclusionSustained long-term excessive drinking can lead to alcoholism and serious liver injury; garlic polysaccharide has significant protective effect on chronic alcoholism liver damage, the mechanism is related to its enhanced antioxidant capacity. |
