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The Research on the Level of Apolipoprotein A5, the Expression of PPAR Gene and the Effect of Rosiglitazone in Diabetic Rats

Author: GaoJie
Tutor: QuXiaoBing
School: Central South University
Course: Geriatrics
Keywords: Apolipoprotein A5 Diabetes mellitus Rosiglitazone Peroxisome proliferator-activated receptor
CLC: R587.1
Type: Master's thesis
Year: 2008
Downloads: 87
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Abstract

BackgroundApolipoprotein A5(ApoA5),a new member of lipoprotein family,has been identified by comparative sequencing of human and mouse DNA in the ApoA1/C3/A4 gene cluster in 2001.ApoA5 is the first discovered lipoprotein which lowers serum triglyceride levels when overexpressing.Now it was observed in the animal and human study that ApoA5 not only effected the metabolism of lipid,but also correlated with the level of insulin.It was indicated that ApoA5 had close correlation with the glycose and lipid metabolism.Type 2 diabetes mellitus(DM)always complicates with the metabolic disorder of hyperglycemia,hypersinsulineima,hypertriglycerideemia and so on;And cardiovascular diseases continue to be a major cause of morbidity and mortality in diabetic patients.It is the global consensus that DM has been regarded as the equal danger disease of coronary heart disease. Rosiglitazone(RSG)is the effective drug to treat DM and metabolic syndrome now.However,until now there is few reports about the expression of serum ApoA5,its regulatory factors and its clinical significances.So it is great important to study the level of serum ApoA5 and to realize its effect in glycose and lipid metabolism and its possible regulatory mechanism.ObjectiveThe aim of this study was to investigate the level of serum ApoA5 and the expression of the PPARαmRNA and PPARγmRNA in the liver by the intervention of RSG in the type 2 diabetic rats;and to investigate the correlations of serum ApoA5 level and the expression of the PPARαmRNA and PPARγmRNA in rats;and to explore the effect of ApoA5 on the glycose and lipid metabolism and its possible regulatory mechanisms.MethodsForty male healthy Sprague-Dawley(SD)rats were chosen as study objects.And establish the animal model of four groups which are control group,high fat chow group(HF group),diabetes mellitus group(DM group) and diabetes mellitus with rosiglitazone intervention group(RSG group). Fasting blood glucose(FBG),fasting insulin(FINS),Homeostasis model assessment of insulin resistance(HOMA-IR),triglyceride(TG),total cholesterol(TC),high density lipoprotein-cholestero(HDL-C),low density lipoprotein-cholestero(LDL-C)and free fat acid(FFA)were measured at the beginning of the study.The diabetic rats’ model was established in accordance with the method of Zhou etc,which was feeding high fat chow and intraperitoneal injection of streprozotocin.And then the diabetic rats were randomly treated with rosiglitazone by daily gavage for 8 weeks.All the rats were killed at the end of the fourteenth week,and collect the blood preparation and tissue preparations of the liver.Then examine the level of FBG、FINS、HOMA-IR、TG、TC、HDL-C、LDL-C and FFA;and measure the level of ApoA5 in serum by enzyme linked immunosorbent assay(ELISA) and analyze the correlations of serum apoA5 level and FBG、FINS、HOMA-IR、TG、TC、HDL-C、LDL-C and FFA.Reverse transacription polymerase chain reaction(RT-PCR)was used to PPARαmRNAand PPARγmRNA expressions in the liver in rats;And analyze the correlations of serum apoA5 level and PPARαmRNAand PPARγmRNA expressions.Results1、Compared to control group,serum ApoA5 concentrations in HF group, DM group and RSG group were decreased significantly,serum ApoA5 concentrations in DM group were the lowest;and compared to DM group, the concentrations in RSG group were increased.All the differences have statistical significance(all the P＜0.05).2、The level of serum ApoA5 negative correlated with TG(r= - 0.781,P =0.000),TC(r=-0.643,P=0.000),FBG(r=- 0.758,P = 0.000),FINS (r=-0.578,P=0.001),HOMA-IR(r=-0.798,P=0.000)significantly; and the level positive correlated with HDL-C(r=0.469,P=0.010) significantly;while the level had no correlation with LDL-C(r=-0.323,P= 0.088)and FFA(r=-0.329,P=0.082).3、PPARαmRNA and PPARγ,mRNA were both detected in the liver;the expression of PPARαmRNA in DM group were the lowest and the expression of PPARγmRNA in DM group were the highest(all the P＜0.05); and compared to DM group,PPARαmRNA in RSG group were increased markedly(P＜0.05),and PPARγmRNA in RSG group were decreased markedly(P＜0.05).4、The level of serum ApoA5 positive correlated with the expression of PPARαmRNA(r=0.577,P=0.001)and negtive correlated with the expression of PPARγmRNA(r=-0.593,P = 0.001)in liver.Conclusion1、The level of serum ApoA5 decreased significantly in diabetic rats,and RSG up-regulated the level;And the level of serum apoM negtive correlated with TG、TC、FBG、FINS、HOMA-IR and positive correlated with HDL-C significantly.It was indicated that ApoA5 may participate the glycose and lipid metabolism and may be regulated by rosiglitazone.2、PPARαmRNA and PPARγmRNA were both expressed in the liver of the rats;The expression of PPARαmRNA in DM group were the lowest and the expression of PPARγmRNA in DM group were the highest;PPARγ,agonist could regulate the expressions of PPARαmRNA and PPARγmRNA in diabetic rats;And the level of serum ApoA5 positive correlated with the expression of PPARαmRNA and negtive correlated with the expression of PPARγmRNA in liver of the rats.It was indicated that the level of ApoA5 may be regulated by PPAR.

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