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The Relationship Between Fatty Acid-binding Protein And Nonalocholic Fatty Liver Disease And And Medication In Research

Posted on:2011-05-27Degree:MasterType:Thesis
Country:ChinaCandidate:L Q LiangFull Text:PDF
GTID:2144360305978751Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Objective:Nonalcoholic fatty liver disease is nothing to do with the excessive drinking, clinical syndrome characterized by excessive fat storing in liver and hepatic cellular dif-fuse steatosis. There has been an increase in the incidence rate of NAFLD, and it may occur in very young children, it has become a global public health problem. However, the mechanisms of NAFLD is not clear, there is still no effective treatment. There is no effective therapeutic tool. The current study found that L-FABP is closely related to high hypertriglyceridemia, hypercholesterolemia, obesity,2-diabetes. Through high-fat diet, this study establish the non-alcoholic fatty liver rat model, in order to observate the ex-pression of L-FABP in the formation of NAFLD; to investigate the effect of L-FABP in pathogenesis of NAFLD; moreover, to observe if traditional Chinese medicine-Jiangz-hi Yigan Chongji can treat and prevent NAFLD through regulating the expression of L-FABP mRNA, explore the molecular therapeutic mechanisms, This investigation can pro-vide more reliable experimental evidence for clinical treatment.Methods:1. Modeling and specimen collection:80 male Wistar rats, weight is about 160-220g, after adaptive feeding 1 week, began to officially experiment.There were ran-domly divided into 8 groups, each group has 10 rats. Normal group (N group) were fed standard diet. Model group(M group) were fed with high-fat and high-cholesterol di-et. Every day in the time of 8:00~9:00am,4:00~5:00pm for the feeding and administra-tion. The eating and drinking of experimental animals is free. Treatment group(Di group) were given Jiangzhi Yigan Chongji 16g·Kg-1·d-1 (calculate the dose in rat by the dose of an adult 60kg body weight, about 40g/d, twice every day, intragastric administration) while fed with high-fat and high-cholesterol diet, a total of 8 weeks; Treatment group (D2 group) were given Jiangzhi YiganChongji(the dosage and usage the same as D1 gr-oup) after the beginning of the study 8 weeks, a total of 4 weeks; meanwhile, the nor-mal and model group were separately given life drinking water by the samemeans. All the rats were sacrificed after 4,8 or 12 weeks. Before all rats were killed, overnight fasting and used pentobarbital anesthesia, abdominal aortic blood,-70℃refrigerator fr-ozen. 2.Measurement Indicators:The following parameters were observed dynamically in each group:body weight, liver and spleen weight, body lenth were detected, at the same ti-me, the retios of liver and spleen, liver index and Lee's index were calculated; the lev-el of aminotransferase, blood fat and lipid in liver tissue were detected by using autom-atic biochemistry analyzer; serum and liver free fatty acid were detected by copper stai-ning method; fasting blood glucose was detected by glucose oxidase method; serum ins-ulin were detected by radio-immunity assay, simultaneously the insulin sensitivity index was calculated; assessing the extent of fatty degeneration with light microscope; The expression of L-FABP mRNA were assayed with reverse transcriptase-polymerase chain reaction(RT-PCR).Results:1. In normal group(N1, N2, N3 group), the structure of hepatic lobule is integr-ited, cells were polygonal, and the central veins radiate, sinusoids clearly visible, liver cable arranged in neat rows, every biochemical manifestation was all in normal range, the expression of L-FABP mRNA was observed in liver.2.After 4 weeks, in model group(M1 group), hepatic histopathology show in hepatocyte light steatosis, compared with the normal group, ALT, ALT, TC, TG and FFA increasin-g, occurs lipid metabolic disorder; FBG, FINS began to increase, ISI decline, appears insulin resistance; in model group, the expression of L-FABP is higher than nomal gr-oup.3.After 8 weeks, model group(M2 group) showed that moderate fatty degeneration of liver tissue, forming simple fatty liver, hepatic steatosis major in Bullous; serum transa-minase(ALT, AST), blood lipids(TC, TG, FFA) was significantly higher than the normal group; the expression of L-FABP mRNA was significantly higher than the normal group in the same period(P<0.01).4.After 12 weeks, in model group(M3 group), hepatic steatosis is sharply increased, an-d the emergence of hepatocyte completely ballooning, lobular mixed with inflammatory celll, as well as scattered point-like necrosis; compared with normal group, serum trans-aminase, total cholesterol and triglyceride were significantly increased; compared with normal group, the expression of L-FABP mRNA was significantly higher(P<0.01).5.Compared with normal group, in treatment group(D1 group) the lever of cell morpho-logy, blood lipids, liver transaminases and the expression of L-FABP mRNA were no statistical differences; but compared with the same period in the model group(M1 grou-p), every indicators have improved, and there is significant statistical difference(P<0.01). 6. Treatment group(D2 group), liver tissue was still visible cable strips arranged in liver cells; compared with the same period in the model group, the degree of fatty change has significantly reduced, only slight inflammatory cell infiltration, no significant necros-is; compared with the M2 group, ALT, AST, TC, TG was improved remarkably, FBG, FINS significantly reduced, the expression of L-FABP was significantly lower(P<0.01).Conclusion:1. The rats model of NAFLD could be successfully established with high-fat and high-cholesterol diet; Insulin resistance and disturbance of lipid metabolism were well associated with the development of NAFLD.2. Normal rats liver can be expressed fatty acid-binding protein. In NAFLD rat model, the expressiong of L-FABP is increased, and with the extension of modeling time, the expressiong of L-FABP is significantly higher.3. In early times of NAFLD, given Jiangzhi Yigan Chongji can effectively prevent the genesis and development of NAFLD.4. JYC can reduce the level of ALT, AST, TC, TG, FFA promote the liver function re-vival. It's show that the drug can not only reverse the liver lipid deposition, but also has a very good role in reducing enzyme and protecting liver; JYC can reduce the lev-el of FBG, FINS, it confirmed that the drug can achieve effective treatment effect on NAFLD throngh improve insulin resistance; and the expression of L-FABP mRNA was significantly reduced, indicating that JYC can be adjusted lipid metabolism, reduce the fatty degeneration of hepatic cells, so as to achieve purposes of treatment.
Keywords/Search Tags:nonalcoholic fatty liver, fatty acid-binding protein, Jiangzhi Yigan Cho-ngji
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