To Study The Correlation Between R2* Values And The Expression Of HIF-1? In Renal Tissue Of Early Diabetic Nephropathy

ObjectiveTo study the correlation between R2* values and the expression of HIF-1? in renal medulla of early diabetic nephropathy in stage ? and stage ? using blood oxygenation-level dependent MRI. So as to determine the feasibility of assessment the level of HIF-1? expression with R2* values in early diabetic nephropathy, and provide accurate noninvasive imaging methods to diagnosis and evaluation of early DN.Materials and Methods16 healthy male SD rats were randomly divided into diabetic group of 10 rats (DN group) and normal control of 6 rats (NC group), we intraperitoneal inject streptozotocin in DN group to establish the model of diabetic nephropathy. Finally,there have seven DN rats which modeled successfully and surviving along and six NC rats underwent MR scan,The scan sequences include axial T2WI, TIWI and BOLD sequence.After completed scan we killed all rats immediately and collected samples drespectively of the double kidney tissue for pathological sections?staining?immunohistochemical and PCR detection. All MRI images were transferred to the post-processing workstations(GE AW Workstation 4.4) for processing.Two experienced radiologists under double blind observed image,then measured and analysis of the double kidney cortex and medulla R2* values in each rat. Using Independent samples t-test to compare general situation, biochemical tests, HIF-la protein and HIF-la mRNA expression values between the two groups; Using the ICC statistical analysis of all measurement data to test the two physicians repeatability; The DN group and NC group cortex and medulla R2* values were compared by Mann-Whitney U test; The correlation between the medulla R2* value and the value of HIF-la mRNA expression were tested by Pearson correlation coefficient in DN group.Results1. General situation:There were no significant differences in the weight of the two groups of rats before modeled (P>0.05), the average body weight of the two groups was significantly different after the model (P<0.05), the difference in 24h urine volume between the two groups was statistically significant (P<0.05).2. Biochemical tests:The difference in serum creatinine, urine creatinine was not statistically significant (P> 0.05), the difference of creatinine clearance in the DN groups compared with group NC was showing significantly (P<0.05). Two groups of rats urine micro albumin were negative.3. DN group and NC groups cortical R2* values of pairwise comparisons showed no statistically significant (P> 0.05), in contrast,the two groups medulla R2* values were showed statistically significant differences (P< 0.05).4. Pathological examination:All of the 14 cases of DN kidney section appeared mesangial cells mild hyperplasia (100%) and tubular expansion (100%).6 of 14 kidneys appeared the glomerular basement membrane thickening (42.86%), and 3 of 14 kidneys appeared glomerulonephritis mild atrophy (21.43%). All of the kidneys in the NC group were normal.5. Immunohistochemistry and PCR detection:The two groups of rat kidney tissue HIF-1? average optical density difference was statistically significant (P<0.05). Similarly,the HIF-1? mRNA gene expression values difference bewteen the two groups was statistically significant (P<0.05).6. The medulla R2* value of DN group and the value of HIF-1? mRNA expression showed no significant correlation (r= 0.356, P= 0.247> 0.05).Conclusions1. BOLD MRI is feasible in the evaluation of the level of oxygenation and hypoxia in early DN.2. BOLD MRI technology can discover kidney function changes earlier than the appearance of microalbuminuria.3. There were no significant correlation between the DN renal medulla R2* value and the HIF-1? expression.