RESUMO
Aim To investigate the effect of Exendin-4 high glucose and the function of silent information reg- on endothelial progenitor cells ( EPCs) induced by ulator 1 (SIRT1 ).Methods EPCs were isolated and cultured by density gradient centrifugation from peripheral blood of healthy volunteers.Different concentrations of Exendin-4( 12.5, 50, 100, 200 (xmol • L"1) induced EPCs were respectively performed by activity test to select the appropriate concentration.The optimal concentrations of Exendin-4 and high glucose (25 mmol • L 1) were incubated together for 72 h to detect the functional activities of EPCs.The capabilities of migration, adhension and tube formation of EPCs in vitro were detected respectively.The levels of LDH and MDA in EPCs were detected.The mRNA expressions of TNF-a, 1L-1 p and IL-6 in EPCs were measured by real-time fluorescent quantitative PCR ( RT-qPCR ).The protein expression of SIRT1 , P53 and Ac-P53 in EPCs were determined by Western blot.Results Ex- endin-4 could increase the viability of EPCs induced by j J high glucose in a dose-dependent manner, especially for 50 (xmol • L "1 (P <0.05 ).Hie results of Western blot showed that the protein expression of SIRT1 was significantly enhanced by 50 |xmol • L"' Exendin-4 treatment ( P < 0.05 ).Compared with high glucose group, Exenclin-4 significantly increased the migration, adhesion, tube formation of EPCs (P<0.05) and decreased the level of LDH and MDA ( P < 0.05 ).The mRNA expression of TNF-cx, lL-(3 and IL-6 in EPCs also decreased (P < 0.05).However, the protective effects of Exendin-4 could he significantly blocked by SIRT1 inhibitor ( EX-527) (P<0.05).In addition, the S1HT1 agonist ( SHT1720 ) could also improve the dysfunction of EPCs induced by high glucose ( P < 0.05).Conclusions Exendin-4 can improve the viability of human EPCs, restore the EPCs normal function, reduce high glucose-induced oxidative damage, and reduce the releases of inflammatory cvtokines un- j j der high glucose condition, which may be related to the regulation of S1HT1/P53 signaling pathway.