Study On The Function Of Nrf2in Vascular Calcification In ESRD

Objective:To analyze the levels of several markers of oxidative stress and antoxidative stress in end stage renal disease (ESRD) patients,and then to characterize the relationship during oxidative stress, antoxidative stress and vascular calcification in ESRD patients.Methods:Twenty-nine patients with ESRD were included in our study and pieces of radial arteries were taken during the arteriovenous fistula operation.Six patients with upper extremity injuries and normal renal function were chosen as control. Pieces of internal radial artery were taken in the operation. The vessels were examined for calcification by alizarin red staining and for the presence of bone matrix protein(osteopontin,OPN),marker of antoxidative stress (nuclear factor erythroid-2-related factor2,Nrf2),marker of oxidative stress(malondialdehyde-LDL,MDA-LDL),Runx2,SM22a,receptor for advanced glycation end products(RAGE) by immunohistochemistry.Detected advanced glycation end products(AGEs) in plasma.Then analyzed the reasons for the abnormalities of the indicators, and the relationship with the other factors which includes sexy、age、history of diabetes、BMI (body mass index)、BUN、Cr、HB、PTH、Ca、P、ALP、ALB、 CHOL、TG、HDL、LDL、hs-CRP and so on. Finally,comparison between groups by t-test (normal quantitative variables), analyze the risk factors of the abnormalities of the indicators by the Logistic regression analysis.Results:Vascular calcification was found in the media of the vessels of15uremic patients,while none in controls.OPN,MDA-LDL,RAGE and Runx2expressed in the vessels and plasma levels of AGEs of uremic patients were significantly higher than those in control,while Nrf2and SM22a expressed in patients with ESRD was significantly lower than those in control(P<0.01).Pearson correlation analysis showed that the extent of calcification was strongly associated with plasma AGEs (r=0.838, P<0.001), MDA-LDL (r=0.922, P<0.001), RAGE(r=0.911, P<0.001)、Nrf2(r=-0.711, P<0.001), plasma phosphate(r=0.623, P=0.001), serum iPTH(r=0.398, P=0.032), age(r=0.591, P=0.001), duration of dialysis (r=0.437, P=0.018). ConclusionDecreased Nrf2which expressed in the vessels were found in patients with ESRD,the Nrf2levels were closely related to vascular calcification which maybe induced by AGEs-RAGE Signal Transmission.