Effect Of TFA On SIRT1/PGC1-?/Nrf2 Signaling Pathway In Rat Vascular Injury

Objective: The purpose of our study was to investigate whether the intake of low-dose trans fatty acids may cause damage to the blood vessels and how it occurs.Method: Totally 48 healthy SD rats weighting 180 g in half genders were adaptively fed for one week.The animals were randomly divided into control group(ND),1% TFA group(LTD),4% TFA group(HTD),each group containing 16 rats.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,all rats were starved for 12 h and sacrificed,then blood samples were collected into the non-anticoagulant tube and the serum lipids were measured by automatic biochemical analyzer.The vascular tissues of rats was isolated,six rats vessel in each group were used for pathology slides to observe changes of vascular morphology and three rats vessel in each group were used for frozen section to observe hyperoxide production in vessel tissues.The remaining vascular tissues were tested the expression of SIRT1,PGC1-?,PPAR?,NOX4,Nrf2,Bcl-2,Bax,caspase3 and cleaved-caspase3 protein were measured by Western blot.Data were expressed as mean±SD.One-way ANOVA test was performed on SPSS20.0 software.The level of significance adopted was p<0.05.Results:1.There was no significantly difference in weight between the three groups fed on different experimental diets(P>0.05),while feed intake and weight increased with age.Blood pressure were measured at 0,6,12 weeks revealed no statistically difference between the groups(P>0.05).2.The levels of TG in LTD group and HTD group were significantly higher than ND group(P<0.05);the content of LDL in HTD group wassignificantly higher than ND group(P<0.05).3.The results of HE staining showed that the vascular tissue of all groups was normal and neatly arranged.There are no significantly change in vessel tissue.4.The Immunofluorescent techniques exhibited a marked acceleration of ROS productionin abdominal aorta owing to 4%TFA feeding.5.Western blot analysis showed that the level of SIRT1,PGC1-?,PPAR?,NOX4 and Nrf2 significantly decreased in HTD-fed groups of rats(P<0.05),comparing with rats in ND group.6.The westren blotting showed that the level of Bcl-2,Bcl-2/Bax ratio and caspase3 decreased significantly in LTD and HTD-fed groups of rats(P<0.05),while Bax,Bcl-2/Bax and cleaved-caspase3 increased markedly in HTD-fed groups of rats(P<0.05).Conclusions: We suppose that low-dose of TFA could induce oxidative stress through SIRT1/PGC1-?/Nrf2 signaling pathway,and induce apoptosis in rat vessel.