| Objective:As the pathogens is remaining incompletely understood yet , diabetic nephropathy still lack the measure of treating with effective system,and account for high mortality rates in patients with diabetes mellitus. The effect of advanced glycation end products (AGEs) produced under the hyperglycemia environment of the diabetes mellitus and its receptors such as receptor for advanced glycation end products (RAGE) , galectin-3 , P60, P90, CD36 etc on kidney in the pathogenesis of diabetic nephropathy has attracted more and more attentions of scholars around the world. As one of the risk factors for diabetic nephropathy , hyperhomocysteinemia, commonly accompanying with diminution of the serum folic acid , vitamin B12 , could be reduced by oral folacin supplementation. But it is under known yet that folic acid could impact on AGEs and its receptors. Therefore, in this study the role of treatment with folic acid on AGEs and its receptors in renal tissue of diabetic rats will be observed.Methods:Fifty adult male Wistar rats, except control group (N,n=9), were made diabetic by a single injection of streptozotocin (STZ) at a dose of 55mg/kg body WT. Diabetic rats were randomized into diabetes mellitus group (DM,n=19) and folic acid group (FA,n=19).After 2 weeks,FA group was accepted oral folic acid supplementation according to 5.0mg/kg body weight. Several biochemistry indexes such as blood urea nitrogen , glucohemoglobin , serum creatinine, 24h urinary protein and BUN/Scr, creatinine clearance rate were detected at the end of 8 weeks.The fluorescence microscope was utilized to survey AGEs fluorescence intensity (exposor time) in iced slices. The expression of RAGE , galectin-3 in rats' renal tissue slices were measured byimmunohistochemistry.The quantitative analysis of staining intensity concluding positive cell optics density and positive cell rate was carried out by MCID Analysis Evaluation 7.0 image analysis process. Statistical significance was evaluated by one-way analysis of variance followed by the One-Way ANOVA tests for multiple comparisons.All datum were analyzed by SPSS 10.0 statistical process. Results:1 > Random blood glucose in DM and FA group diabetic rats was obviously elevatory vs control group at 4> 6n 8 weeks, while body weight was degressive(P<0.05 or P< 0.01).Obviously difference in blood glucose and body weight between diabetic rats were not founded(P> 0.05).2 s At 8 weeks BUN,BUN/Scr, GHb>24h UP(P<0.01) in diabetic groups vs control group were uplifted, on the contrary , creatinine clearance rate (P<0.01 or P<0.05)was decendent.Only 24h UP had difference between FA group and DM group(P<0.01).3 > Fluorescence detection prompted that AGEs fluorescence intensity was lowest in control group. Conversely The intensity of AGEs fluorescence of FA group also obviously rises more than N group (P<0. 01) But obviously reduce than DM group (P< 0.01).4 s Galectin-3 protein was not detectable in glomeruli from nondiabetic rats even in the end of study. On the contrary,Galectin-3 expression in diabetic rats was observed at 8 weeks of disease duration.Differently, Galectin-3 was expressed in tubuli from both nondiaetic and diabetic rats.Fouthermore , galectin-3 staining positive cell rate and optics density in glomeruli and tubuli obviously rise in FA group comparing with DM group (P <0.05) .5> Expression of RAGE was not detected in tubuli both from nondiabetic and diabetic rats,but there was opposite conditions in glumeruli. Comparing with DM group,FA group had less RAGE staining positive cells in slices (P<0.05) .Conclusion:1 > Folic acid supplementation could not evidently affect random body weight,blood glucose and some biochemistry indexes. The difference in 24h UP between FA group and DM group indicates folic acid possibly improves clinic symptom of diabetic nephropathy.2, Since the AGEs fluorescence intensity in slices from FA group was descended vs DM group,it is concluded that folic acid which could alleviate the accumulation of advanced glycation end products in kidney of diabetic rats will possibly protect renal tissue from impairment induced by AGEs and its receptors.3 % Folic acid intake could upregulate expression of galectin-3 in kidney of diabetic rats.but downregulate expression of RAGE comparing with diabetic rats which did not recept treatment with folate.lt suggests that folic acid could be related with the pathogenesis of diabetic nephropathy through varying expression of receptors for advanced glycation end products as one way of renoprotection in diabetes.Thus this study may provide new therapeutic strategies for diabetic nephropathy and shed new light on the pathogenesis of diabetic nephropathy.
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