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The Therapeutic Effect and the Influence of the ERS Regulated Factors Research of QiWeiTieXie Capsule on Non-alcoholic Fatty Liver Rats

Author: ChenZuoDi
Tutor: ChenDongFeng
School: Third Military Medical University
Course: Department of Gastroenterology,
Keywords: Fatty liver disease Non-alcoholic QiWeiTieXie capsule Polyenephosphatidylcholine capsule GRP78 SREBP-1c Caspase-3 TNF-α
CLC: R575.5
Type: Master's thesis
Year: 2012
Downloads: 20
Quote: 0
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Abstract


Background and Significance:Non-alcoholic fatty liver disease (NAFLD), refers to the diffuse liver cell steatosisbullous clinicopathologic syndrome without the history of excessive alcoholconsumption,viruses,drugs, and other definite liver damage factors.NAFLD is the secondlargest chronic liver disease in China,which after viral hepatitis.It is the main course ofasymptomatic transaminase is elevation, has become a widespread concern of the scholars.Currently there is no effective drug to treat clinical NAFLD. Chinese tradional medicinegenerally considered that the NAFLD was caused by improper and unhealthy diet,obesity orexcessive drinking,resulting in the air-blocking inside,inner heat,and block the livernetwork.Therefore, the treatment should mainly be dredging the liver,activating theblood,getting rid of the inner phlegm and dampness.QiWeiTieXie capsule is mainlycomposed of seven kinds of herbal drugs,which are separeately scrap iron, gypsum,Tibetinulae,costustoot,dracocephalum tanguticum maxim, safflower carthamus,trogopterusdung.The main effect of this drug is to promote blood circulation,and reduce the burden onthe liver.It can treat the characteristics of fatty liver disease.However the mechanism is notcompletely clear.Therefore,finding a drug to treat non-alcoholic fatty liver disease anddelay the process has become a medical hot topic,especially in the field of liverdisease.So,in order to research whether the QiWeiTieXie capsule is effective in NAFLDand to preliminary explore its mechanism,the QiWeiTieXie capsule made from traditionalTibetan medicine is used to treat the rats with NAFLD caused by simple high fat die.Alsoadopt the technologies of HE staining,Western blot and others to observe the pathologicaland histological character and levels of serum AST,ALT,TG,FFA,and the protein expression levels of liver tissue GRP78,SREBP-1c, Caspase-3and TNF-α.Objective:NAFLD rats which caused by simple high fat die were chosen.To observe the effectof QiWeiTieXie capsule on non-alcoholic fatty liver disease (NAFLD)in rats after12weekstreatment,and preliminary discuss on its mechanism.Methods:60Wistar rats of4weeks old,were randomly divided into four groups:①normalgroup:Using basic chow.②Model group: high fat diet.Respectively choosing18rats fromeach of two groups abover,at4weeks (3),8weeks (3),12weeks (12) in which4weeks,8weeks specimens were used to verify whether the NAFLD modelingsucceed.③Q iWeiTieXie capsule treatment group:high fat diet combined QiWeiTieXiecapsule feeding.④Polyenephosphatidylcholinecapsule positive control group:high fat dietcombined Polyenephosphatidylcholine capsule feeding.Respectively choosing12from eachof Q and P group of12weeks.Using HE staining light-microscopy to obersve rat liverpathological histology changes.Automatic biochemical analyzer test every group of theratserum alanine aminotransferase (ALT),aspartic acid transaminase (AST),triglyceride(TG),free fatty acid(FFA) level.Using Western blot method to detect the rat liver tissueGRP78,SREBP-1c,Caspase-3,TNF alpha protein expression quantity.Result:1.The general observation of all the groups of rats after12weeks.N group rats: the fur is luster, the body size and activities are normal.F group rats:thefur is gloss,low activity, plump body and slow response.Q group and P group rats: the fur iscomparatively less luster,normal activity,body size and response are between normal andmodel group.2.Comparison of every group of the changes in liver appearance after12weeks.N group rats:liver surface is smooth,bright red color,sharp edges.F Group rats liver eyeview of volume increases,pale yellow color,soft and tough texture,capsular tension, bluntingthe edge,cut the greasy feeling.Q and P group rats:liver light yellow color, texture,volumerange between normal and model group,obvious difference by the naked eye. 3.Comparison of the12weeks rats liver index.Modeling after12weeks.Group F rats liver index was significantly higher than the Nrats(P<0.01).Q and P groups compare with Group F rats liver index was significantlyreduced,the difference was statistically significant.4.12weeks in each group of rats liver histopathological changes,the degree of hepaticsteatosis and inflammation score.The N group rats has clear structure of hepatic lobule,hepatic cords neatly arrangedradially, normal liver sinusoidal cell morphology rules, no liver cell steatosis, degree ofhepatic steatosis score was0.00±0.00. Group F rat hepatic lobule structural damage, alarge number of lipid droplets in the liver cells,the degree of hepatic steatosis score of3.75±0.46,statistically significant difference with the N group.Q group P rats hepatic lobuleboundaries unclear, hepatic cord arrangement disorder, steatosis was significantly increased,the degree of hepatic steatosis score of2.50±0.53,2.37±0.51,N group rats liver infla-mmation meter points is0.00±0.00,F rats serious inflammation of the liver,seen scatteredlobular necrosis,heavy inflammation of the portal area.Inflammation scores was3.87±0.35,significantly higher than the normal group.Q and P groups rats liver cells spottynecrosis.Varying degrees of inflammatory cell infiltration in the hepatic lobule,infla-mmation scores are2.62±0.51,2.25±0.46,significantly lower than group F.5.Comparison of the serum biochemical indicators of every group of rats after12weeks.All of F,Q and N groups rats serum AST, ALT,TG, FFA were increased.Comparedwith the group N, Group F serum AST, ALT, TG, FFA levels significantly increased.Compared with the group F,Q and P group rats serum AST,ALT,TG,FFA were significantlyreduced,have significant statistical difference.Compared with groups of Q and P,thedifferences of two groups of serum AST,ALT,TG,FFA have no statistic significance.6.12weeks the rats of GRP78, SREBP-1c, caspase-3, TNF-α protein expressionchanges.Compared with the groups N and F liver tissue GRP78,SREBP-1c,Caspase-3,TNF-αprotein expression was significantly increased.Compared with the group F,Q and P group rats liver tissue GRP78,SREBP-1c,Caspase-3,TNF-a were significantly reduced.Comparedwith group of Q and P, rats liver tissue of the two groups of GRP78, SREBP-1c,Caspase-3expression levels of TNF-α,have no obvious statistic difference.Conclusion:1.Fed high fat diet alone for12weeks,to successfully build rat NAFLD model withliver steatosis,lipid metabolism disorders characteristic performance.2.After12weeks treatment of QiWeiTieXie capsule on NAFLD rats,through the lightmicroscope,serum biochemical tests,it is found that the rat liver steatosis have beensignificantly reduced.The levels of serum AST, ALT, TG, FFA have been significantlydeclined.The QiWeiTieXie capsule made from traditional Tibetan can impove NAFLD ratsliver function,lower blood lipids,correct lipid metabolism disorders,inhibit lipidaccumulation in the liver cells, reduce hepatic steatosis,to achieve to goal of treatingNAFLD.3. NAFLD rat which are treated by the QiWeiTieXie capsule,the liver tissue of GRP78,SREBP-1c, caspase-3, TNF-α protein expression were significantly lowered.It indicatesthat the QiWeiTieXie capsule possibly lows down the expression of GRP78protein level,restores the endoplasmic reticulum steady, to prevent sterol regulatory cascade andapoptosis signaling pathways start,reduce TG accumulation in liver cells,inhibit theinflammatory response,improve liver cell function,reduce hepatic steatosis.This is probablyone of the mechanisms of treating NAFLD.4.By light microscopy,blood biochemistry, Western blot method and softwareanalysis,we found that there is no significant difference in the two NAFLD rats groupswhich treated by the capsule and Polyene phosphatidylcholine capsule.However,the effectsof two groups above were better than F group.It indicates that both medicines havetherapeutical effects on NAFLD rats.

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