Font Size: a A A

Studies On Functional Effect And Mechanisms Of Anti-alcohol And Liver-protection Of Lingzhisuan Granule

Posted on:2012-07-18Degree:MasterType:Thesis
Country:ChinaCandidate:R YaoFull Text:PDF
GTID:2214330368475675Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
General IntroductionAlcohol is one of the most common toxic liver, liver damage caused by excessive drinking is a worldwide medical problem. Have expected that the daily intake of ethanol in adult male dosage of> 40g, female alcohol intake dose> 20-30g, can cause liver damage. Of ethanol into the body, only 2-10% through the lungs and kidneys, most of the remaining principal in the cytoplasm of liver alcohol dehydrogenase, peroxisomal catalase in and microsomes metabolic enzymes in ethanol oxidation to acetaldehyde and then metabolized to acetic acid by aldehyde dehydrogenase into three shuttle acid cycle metabolic carbon dioxide and water. Ethanol metabolism caused oxidative stress, oxidative stress can damage the mitochondria, leading to mitochondrial dysfunction, alcohol can also lead to endoplasmic reticulum stress, and cause mitochondrial dysfunction, lipid accumulation, inflammation and apoptosis. In recent years, the incidence of adult alcoholism also increased. Long-term drinking can cause systemic multi-system damage, particularly in the gastrointestinal tract, liver damage is more obvious, alcohol can directly or indirectly cause chronic gastritis, peptic ulcer and alcoholic cirrhosis. In recent years, studies on the mechanism of ethanol metabolism in significant progress, but the control methods and treatment did not progress, it has not yet led to effective prevention and treatment of alcohol intake clinical and social problems.Garlic granules Ganoderma lucidum extract from the extract, garlic extract, maltodextrin composition. Modern pharmacological and clinical studies have shown that Ganoderma lucidum on a variety of physical, chemical and biological factors of liver injury in rats. Whether the damage occurred in the liver before or after taking Ganoderma can contribute to liver drug, toxin metabolism, protect the liver, reducing liver damage. Large number of chemical components of garlic, both an immune activator, is also a powerful antioxidant. Garlic oil, allicin, garlic polysaccharide on ethanol-induced liver injury were reported, its protection may be related to scavenging free radicals and inhibiting lipid peroxidation and other effects. These reports suggest the fungus, garlic products in the fight against ethanol, the potential role of injury prevention and treatment, according to the demand for products and liver hangover situation, our group developed the formula of Ganoderma lucidum as raw garlic, garlic granules will have a broad market, we particles by studying the liver Liver Ganoderma role of garlic in order to evaluate its health care function, development and utilization to provide further scientific basis.Objective:To establish Alcoholism and acute liver injury model by given ethanol one time; and chronic liver injury model by Long-term alcohol intake. The Effects and mechanisms of Ganoderma lucidum garlic granules was evaluated by measuring the serum and liver-related indicators and histopathological.Methods:1.Forty mice were divided into four groups:normal group,model group,extract high dosage,middle dosage, and low dosage group.After the mice were orally administered with LZS for 7 days,50% alcohol at a dose of 18mL/kg was given and observe its effect on sober-up time and sleep duration time;Rat were randomly divided into control group and administration group, after given 50% alcohol at a dose of 14mL/kg 30min later, blood was colleted by tail tip cutting(tc) at three points of time for 30,120 and 180 min,and then blood alcohol concentration were measured by gaschromatograph.2. Sixty healthy KM mice were divided into six groups:normal group,model group,extract high dosage,middle dosage,low dosage group,and positive control group.After the mice were orally administered with LZS for 15 days,50% alcohol at a dose of 12mL-kg-lwas given and then sacrificed to Collect serum samples and mice liver tissue samples. The levels of ALT, AST, TG, MDA, GSH were determined respectively, the histopathology were observed at the same time.3.60 SD rats were randomly divided into 6 groups alcohol group(gstrieally infused with Red Star Erguotou once a day with a dose of 15ml/kg body weight for 4 weeks) , positive control group(1.5ml/100g/day wine+2.36mg/kg/day DDB) low-dosage LZS group(1.5ml/100g/day wine+0.1lg/kg/dayLZS),middle- dosage LZS group (1.5ml/100g/day wine+0.21g/kg/dayLZS), high -dosage LZS group (1.5ml/100g/day wine+0.42g/kg/dayLZS) and control group(gastric infusion with normal saline), At the end of 4weeks blood samples were collected and then the rats were sacrificed. The serum AST,AST,TG and the pathological changes,were exmined to assess the protection of LZS; Preparing1 0% liver homogenate for the examination of the MDA and reduced GSHcontents, and the activities of theSOD;.Isolation and Purification of mitoehondria by differential cenirifugation for the determination of the SOD as to detcete for the antioxidant system assay; Isolation and Purification of microsome by ultracentrifugation for the determination of protein levels of CYPZEI and GSH-px.Results:1. anti-alcohol experiments show that:LZS could differently prolong sleep duration time and shorten sober-up time.especially the high-dose group and the middle-dose group,compared with the model,these two groups can significantly prolong the sleep duration time(P<0.05), shorten sober-up time (P<0.05); GC-MS was used to determin the content of ethanol in blood after infused with 50% acholo the results showed:the concentration of ethanol was less in treatment group at each time point than the control group, which 120min,180 min compared with the control group significantly (P<0.01), treatment group the curve of peak area is less than the control group.2. Acute alcoholic liver injury results show that:Ganoderma garlic granules treatment group was significantly lower in serum ALT, AST and MDA, increased GSH levels. compared with model group, ALT (P<0.01), AST (P<0.05), TG (P<0.01) decreased significantly, GSH was significantly higher (P<0.01) in high-dose group;ALT was significantly lower (P<0.05), GSH content was significantly higher (P<0.01) in middle-dose group; GSH levels in liver homogenates was significantly higher (P<0.01) in low-dose group. The pathological sections showed that liver injury was reduced to different extent after LZS treatment,the high dose is most significant:Expansion of the central vein lobule in model group, sinusoidal congestion and hemorrhage, hepatic cells was swelling, diffuse fatty degeneration of liver cells;Positive control group organizational structure of hepatic lobule close to the normal, no significant swelling of liver cells, liver cells in cord neatly arranged, but still shows a small amount of congestion; low dose of liver cell swelling, a lot of fatty degeneration of liver cells; around the central vein in the dose group part of the fatty degeneration of liver cells, lesions smaller, to reduce swelling; lobular arrangement of the high dose group than homogeneous, and no clear sinuses narrow, occasionally scattered in the hepatic steatosis. Pathological morphology suggest that Ganoderma garlic granules on alcohol induced liver lipid peroxidation has a protective effect, especially in the high- dose group indicating that the drug in acute alcoholic liver injury have a therapeutic effect, and its of alcoholic liver injury may be the mechanism of antioxidant and free radical scavenging.3. Chronic alcoholic liver injury results show that:45 days of alcohol intake in rats, body weight decreased significantly (P<0.01), AST, ALT and MDA increased significant (P<0.01). LZS can significantly alleviate the damage, especially in the high-dose group.compared with model group, a significant rebound in body weight of rats (P<0.01); ALT (P<0.05), AST (P<0.01), TG (P<0.01) has decreased significantly; MDA in both serum and liver tissue was significantly lower (P<0.01), GSH was significantly higher (P<0.01); GSH-px, (P<0.05), SOD activity in mitochondria has increased (P<0.01), CYP2E1 activity in microsomal has decreased (P<0.01), GSH-px levels rose significantly higher (P<0.05). LZS exhibit normal antioxidant system, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and glutathione-s-transferase (GST) were within the normal range. Paraffin section of liver pathology showed:model group, liver histology in serious injury, significant swelling of the liver cell cytoplasm loose, large and small cytoplasm can be seen, varying amounts of lipid droplets and associated with ballooning degeneration and cellular edema, lobule structural disorder, a bit like lobular necrosis; low dose group was swelling of liver cells, the cytoplasm shows large and small, ranging from the number and accompanied by ballooning and cell edema, hepatic lobules disorder; middle dose group rat liver cell swelling, cytoplasmic lipid droplets within the visible and accompanied by a small amount of mild ballooning degeneration, lobular architecture, basic and complete; high-dose group; rat liver cells, lobular architecture was normal, which garlic granules that can ease the fungus damage of alcohol can significantly reduce the alcohol on the body lipid metabolism and antioxidant system of adverse effects.Conclusions:1.The anti-alcohol experiment and the test of Determination of ethanol content in blood show that, LZS can prolong the varying degrees of drunkenness time, shorten the sleep time, high dose of the best; LZS can effectively reduce the different time points blood alcohol concentration, and fundamentally ease the symptoms of acute alcoholism, and its mechanism and reduce the absorption of ethanol/alcohol in the body to accelerate the metabolism and excretion2.Ethanol feeding caused a single acute alcoholic liver injury, liver lipid peroxidation increased gradually with time, confirmed that oxidative stress in acute alcoholic liver injury, and is a gradual process of accumulation. In addition, the non-enzymatic antioxidant GSH, SOD activity of antioxidant enzymes were significantly reduced, suggesting that the damage of early antioxidant system increased oxidative stress. Garlic granules Ganoderma lucidum inhibits oxidative stress caused by ethanol, showed significantly reduced lipid peroxidation. In addition, the fungus can also restore GSH content of garlic granules and SOD activity. Therefore, Ganoderma garlic granules can speculate relieve acute alcoholic liver injury caused by oxidative stress may be related to protection of the antioxidant defense system, thereby contributing to effective removal of ROS relevant.3.Long-term alcohol intake in rats can lead to chronic alcoholic liver injury, liver cells, ethanol induction of hepatic pathological changes and serological changes, including hepatomegaly, with the AST, ALT a significant increase in. LZS intervention group significantly to hepatic parameters returned to normal levels. High dose was more significant. Alcohol intake can lead to liver tissue and serum triglyceride levels increased significantly. LZS intervention can improve the poor results. And alcohol treatment group, LZS intervention could significantly reduce serum and liver triglyceride levels. MDA lipid peroxidation was also significantly increased. Alcohol treatment results in liver tissue and serum MDA levels were significantly increased. AEBR intervention can reduce the synthesis of MDA. Compared with the control group, GSH levels in the alcohol treatment were significantly lower. Antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase GSH-Px, alcohol intake can significantly reduce the activity.Ganoderma lucidum by observing the particles on a one-time alcohol intake of garlic and the intervention of long alcohol intake regulation, that has a good hangover LZS hepatoprotective effect.
Keywords/Search Tags:Lingzhisuan Granules (LZS), Rats, Mice, sober up, Alcohol-induced liver damage, Ethylalcohol
PDF Full Text Request
Related items