The Impact Of Nuclear Vitamin D Receptor On The Inflammation Of Type2Diabetic Nephropathy Patients

Objective:Analyze the correlations among the nuclear vitamin D receptor、NF-κB expressions of peripheral blood mononuclear cell and urinary chemokines excretion rate of MCP-1RANTES, to investigate the impact of VDR on the microinflammation of type2diabetic nephropathy.Method:143subjects were enrolled, including113patients with diabetics and30healthy subjects (NC group). Diabetics were divided into three groups according to the urinary albumin/creatinine ratio (uACR): diabetes normal albuminuria group (DNO group,38cases),microalbumin-uria group (DN1group,38cases), and macroalbuminuria group (DN2group,38cases).urine chemokines were measured by enzyme-linked immunosorbent assay (ELISA). Real time qPCR was used to assess relative expression level of VDR and NF-κBmRNA expression. Western-blotting was used to detect the protein level of nVDR and NF-KBp65.One-way analysis of variance,Pearson correlation analysis and multiple stepwise regression analysis for statistical analysis were used.Result:1. The levels of urinary MCP-1/Cr were914.32±372.21pg/mgCr、414.57±130.93pg/mgCr、196.07±66.27pg/mgCr、101.14±29.47pg/mgCr in DN2group、DN1group、DNO group、NC group respectively, comparative differences between groups were statistically significant;The levels of urinary RANTES/Cr were652.50±293.98pg/mgCr、327.47±191.88pg/mgCr、180.63±67.55pg/mgCr.81.39±27.89pg/mgCr in DN2group、DN1group、DNO group、NC group respectively, comparative differences between groups were statistically significant.2. Urinary MCP-1/Cr、RANTES/Cr were significantly correlated positively with systolic blood pressure (SBP)、blood urea nitrogen (BUN)、serum creatinine (SCr)、uACR, negatively with estimated glomerular filtration rate (eGFR); Multivariate linear regression analyses shows that urinary MCP-1/Cr is independently associated with uACR and eGFR, urinary RANTES/Cr was independently associated with uACR. 3. The relative expression levels of VDRmRNA in DN2group、 DN1group and DNO group were significantly lower than NC group, and it was significantly lower in DN2group、DN1group than DNO group, differences were statistically significant; The protein levels of nVDR in DN2group、DN1group、DNO group were significantly lower than NC group respectively, comparative differences between groups were statistically significant.4. The relative expression level of VDRmRNA was correlated negatively with SBP、FBG、SCr、uACR, MCP-1/Cr、RANTES/Cr, positively with eGFR; The protein level of nVDR was correlated negatively with FBG、SCr、uACR、MCP-1/Cr、RANTES/Cr, positively with eGFR; Multivariate linear regression analyses showed that relative expression level of VDRmRNA was independently associated with MCP-1/Cr and RANTES/Cr.5. The relative expression levels of NF-KBp65mRNA in DN2group、 DN1group、DNO group were significantly higher than NC group respectively,meanwhile DN2group higher than DN1group and DNO group.there was no statistically significant difference in DN1group and DNO group; The nucleoproteid levels of NF-κB p65in DN2group、DN1group、DNO group were significantly higher than NC group respectively, and it was significantly higher in DN2group than in DNO group.6. The relative expression level of NF-KBp65mRNA was positively correlated with SBP、SCr、uACR, MCP-1/Cr、RANTES/Cr, negatively with eGFR and VDR mRNA; The nucleoproteid level of NF-KBp65was positively correlated with SBP、FBG、uACR、MCP-1/Cr、RANTES/Cr, negatively with nVDR protein level. Multivariate linear regression analyses showed that the relative expression level of NF-κBp65mRNA was independently associated with MCP-1/Cr and VDRmRNA.Conclusions:1. the development of type2diabetic nephropathy is closely related to microinflammation.2. The expression of VDR is down-regulated in type2diabetic nephropathy patients,and is related to the development of type2diabetic nephropathy. 3. The down-regulation of nVDR may induce inflammation by over-express NF-κB p65, in turn involve in the development of diabetic nephropathy.