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Effect Of Low-Dose TFA On PPARa/PGC1-a/AKT Signaling Pathway In Rat Heart

Posted on:2018-02-25Degree:MasterType:Thesis
Country:ChinaCandidate:Z LiuFull Text:PDF
GTID:2334330536463444Subject:Nutrition and Food Hygiene
Abstract/Summary:PDF Full Text Request
Objective: Trans Fatty acid(TFA)is the general term for unsaturated fatty acids containing trans-configuration double bonds,mainly derived from synthesis of ruminants in vivo,vegetable oil refining and oil hydrogenation.Hydrogenated fat possess high melting point,good oxidation stability,long shelf life,pleasant taste and other characteristics,which is widely used in food processing.20 century,70 years,the study found that consumption of hydrogenated fat has a relationship with cardiovascular disease.As a result of the increase in processed food consumption,the intake of TFA in China has gradually increased,but a large number of studies have confirmed that TFA can lead to thrombosis,inflammatory response,atherosclerosis,thus induce type 2 diabetes,coronary heart disease,brain function decline,Carcinogenic,etc.Currently,domestic and foreign research relating to the role of trans-fatty acid in cardiovascular disease development have gained prominence,however,molecular mechanism of TFA-induced cardiovascular disease is still unclear.Moreover,there have been several reports on the adverse effect of high concentrations of trans-fatty acid on human health,but research on the effect of low-dose trans-fatty acid on human health is inadequate.This study therefore,seeks to further explore the molecular mechanism of the effect of low concentrations of trans-fatty acid on the cardiovascular system.Method: Totally 48 healthy clean SD rat in half genders,each weight is180 g,were randomly divided into control group(ND),1% TFA group(LTD),4% TFA group(HTD),16 rats in each group.The animals were adaptively fed for one week and measured basal blood pressure.The food intake and body weight were recorded weekly during the experiment,and the blood pressure was measured at 0,6 and 12 weeks,respectively.After 12 weeks of feeding,took away food for 12 h,then weighed the animals,sacrificed all the animalsand collected blood into the non-anticoagulant tube,room temperature for20 min,4000r/min centrifugal 15 min,separated the serum,and stored in-80?.The serum lipids were measured by automatic biochemical analyzer.The heart tissue of rats was isolated,and 6 in each group were used for pathology slides.The changes of cardiac morphology were observed.The remaining cardiac tissues were tested as follows: the activity of SOD and the content of MDA were measured according to the kit instructions;The expression levels of PGC1-?,PPAR?,AKT,P-AKT,Bcl-2 and Bax protein in rat heart were measured by Western blot.Data were expressed as mean ± SD.One-way ANOVA test was performed on SPSS 21 software.Differences were statistically significant when P<0.05.Results:1 Effects of TFA on body weight,food intake and blood pressure in ratsThere was no statistically significant difference in weight between the 3groups of rats fed on different experimental diets(P>0.05)as shown in Fig.1A and 1B though feed intake and weight increased with age.Blood pressure measured at 0,6,12 weeks showed no statistically significant difference between the groups(P>0.05).2 Effects of TFA on Blood Lipid in Rats The levels of TG in LTD group and HTD group were significantly higher than ND group(P<0.05);LDL content in HTD group was significantly higher than ND group(P<0.05).TC and HDL levels in all the three groups showed no statistically significant difference(P>0.05).3 Effects of TFA on PPAR?/PGC1-?/AKT/p-AKT in Rat Myocardial TissueWestern blot analysis showed that PPAR? and PGC1-? expression and p-AKT/AKT ratio in the heart tissues of LTD and HTD-fed groups of rats was significantly lower(P<0.05)than that of ND fed group(P<0.05).4 Effects of TFA on oxidative stress in rat heartCompared with ND-fed group,the MDA content and the SOD activity in heart tissue significantly decreased in LTD and HTD-fed groups(P<0.05),indicating that trans-fatty acid induces oxidative stress in myocardial tissue of rats.5 Changes in cardiac pathologyThe results of HE staining showed that the myocardial tissue of ND-fed group was normal and neatly arranged.LTD and HTD-fed groups demonstrated inflammatory cell infiltration,but no statistically significant difference was observed between the two groups.6 Effects of TFA on Myocardial Tissue Apoptosis in RatsCompared with ND group,expression of Bcl-2 protein significantly decreased in the heart tissue of LTD and HTD-fed groups(P<0.05),however,there was no statistically significant change in Bax protein expression(P>0.05).Bcl-2/Bax ratio significantly decreased(P<0.05),indicating that trans fatty acids induce apoptosis in rat myocardium.Conclusions: Low doses of trans-fatty acids can induce oxidative stress through PPAR? / PGC1-? / AKT signaling pathway,and induce apoptosis and inflammatory cell infiltration in rat myocardium.
Keywords/Search Tags:Trans fatty acids, Oxidative stress, Apoptosis, PPAR?, PGC1-?, AKT
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