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Preventive and Therapeutic Effect of Network Antioxidants on the Rats with Nonalcoholic Steatohepatitis and Mechanism Study

Author: ZhangXiaoLan
Tutor: WenQinSheng;WangXuXia
School: Fourth Military Medical University
Course: Internal Medicine
Keywords: Non - alcoholic steatohepatitis Oxidative stress Antioxidants Lipid peroxidation
CLC: R575.1
Type: Master's thesis
Year: 2008
Downloads: 68
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Abstract


Background non-alcoholic fatty liver disease (non-alcoholic fatty liver disease, NAFLD) is other than alcohol and other clear factors of liver damage caused by diffuse liver cells bullous fat becomes the main feature of the clinical and pathological syndrome , including simple fatty liver, non-alcoholic steatohepatitis (non-alcoholic steatohepatitis, NASH), cirrhosis and liver cancer, chronic liver disease is a common clinical. NASH is a type of NAFLD, by the development of simple fatty liver to liver fibrosis, cirrhosis and even liver cancer a key turning point. Therefore, NASH increasing attention has been paid, however, NASH pathogenesis of complex, has not been fully elucidated, recognized as the \(reactive oxygen species, ROS) oxidation of unsaturated lipid-induced lipid peroxidation can lead to the occurrence and development of NASH. There are still no really effective treatment. Domestic and foreign scholars from the lipid, insulin resistance, and lifestyle adjustment of different treatment methods were based on experiments and clinical studies, but different conclusions, there is also a lot of controversy. Its pathogenesis and interventions particularly urgent. Purpose through the establishment of a high-fat diet-induced rat NASH model, monitoring indicators of oxidative stress in the the NASH pathogenesis of the changes in the assessment of oxidative stress in the pathogenesis of NASH; to network anti-oxidant intervention by repressor oxidative stress observed Nash outcomes clear whether the network antioxidants have a role in prevention and treatment of NASH, to further explore the relationship of oxidative stress in the pathogenesis of NASH. This research through the establishment of a high-fat diet-induced rat NASH model, dynamic observation of changes in liver pathology, liver function, blood lipids and oxidative stress-related indicators, to assess the occurrence of NASH from different angles of the morphology, blood biochemistry, oxidative damage , development, and explore the role of oxidative stress and lipid peroxidation damage in the pathogenesis of NASH. Network antioxidants (vitamin C, vitamin E, coenzyme Q10, lipoic acid, reduced glutathione) to intervene and take preventive medication and treatment medication two modes of administration to observe the outcome of the use of antioxidants NASH further evaluation of oxidative stress, lipid peroxidation in the pathogenesis of NASH and comparison of the two modes of administration for the impact of the disease outcome, to explore the relationship between the timing of administration with NASH progress; establishment of metformin, fluvastatin statin therapy control group, observed from the horizontal, compared to the outcomes of the three different types of drug treatment NASH, from a different point of comparison, selection of optimum treatment plan. Results (1) successfully established a high-fat diet-induced NASH animal models, the HE staining presented to steatosis, accompanied by varying degrees of inflammatory cell infiltration, steatosis and inflammation severity with the modeling time extend gradually intensified, the partial liver fibrosis at 12 weeks; preliminary evidence in NASH development process, oxidative stress, lipid peroxidation damage persists, and was positively correlated with the severity of disease. The experimentally observed in the high-fat diet for 8 weeks ago superoxide dismutase (superoxide dismutase, SOD) activity decreased, with increased aggravation of steatosis and inflammation scoring, MDA (Malondialdehyde, MDA) also tended to increase in SOD activity in a downward trend, and 12 weeks in modeling MDA content increased more obvious. (2) clear network antioxidants for the high-fat diet-induced rat NASH model has a preventive effect was further confirmed by oxidative stress, lipid peroxidation damage an important role in the pathogenesis of NASH. Network antioxidant group of eight weeks, 10 weeks, 12 weeks, serum and liver MDA content with the model group dynamic comparison showed a clear downward trend, SOD activity and dynamic model group showed a clear upward trend in ALT, AST and inflammation scoring compared with model group decreased. (3) the network antioxidants Early application effect is better, the visible lesions early to keep the body strong antioxidant capacity, reduce the damage caused by free radicals, which can effectively control the progression of the disease, the timing of treatment should be chosen early intervention. Serum biochemical detection prompted network antioxidant treatment group AST, MDA content was significantly higher than the prevention group, SOD activity was significantly lower than the prevention group; Histopathology showed steatosis and inflammation lesions emphasis on the prevention group. (4) Network antioxidants, metformin and fluvastatin three different drugs for the high-fat diet-induced rat NASH model have some therapeutic effect, the network antioxidants treatment group liver pathology improvement is better than the other treatment groups, but each The treatment method has potential. Network antioxidant treatment of liver tissue with steatosis, inflammation meter points and MDA were lower than the other two groups; fluvastatin group TC decreased compared to other treatment group was significantly; metformin fasting blood glucose, blood insulin levels and insulin resistance index of less than other treatment groups. Conclusion This issue through the successful replication of high-fat diet-induced rat NASH model network antioxidants to start from oxidative stress injury, confirmed the occurrence of NASH, development and oxidative stress, lipid peroxidation damage is closely related. That oxidative stress in the pathogenesis of NASH, lipid peroxidation injury play an important role; the network antioxidants can effectively inhibit lipid peroxidation damage, maintain the antioxidant activity of the SOD enzyme to maintain oxidative - antioxidant balance; early The intervention particularly effective preliminary study of the treatment of NASH should be in line with the principle of early. The results provide preliminary experimental data and theoretical basis for further explore the pathogenesis of NASH and new therapeutic direction.

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CLC: > Medicine, health > Internal Medicine > Digestive and abdominal diseases > Liver and gall bladder disease > Hepatitis
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