Effects Of Hedysarum Polybotrys Polysacchcaide On The Expression Of VEGF And PEDF In Renal Tissue Of Db/db Mice With Diabetic Nephropathy

Objective: By observing the effects of Hedysari polysaccharide (HPS) on the level ofexpression of vascular endothelial growth factor (VEGF) and pigment epithelium-derivedfactor (PEDF) mRNA and protein in the renal tissue of diabetic nephropathy (DN) db/db mice,we objectively evaluate its protective effects, and further to explore its possible mechanisms.Methods:11weeks Male BKS mice with the number of60,50of db/db,10of db/m,were used for this study. The db/db mice aging12weeks were numbered according to theirweight, then divided into5groups: three HPS treatment groups in which db/db mice wereadministered with HPS (dissolved in saline solution) at doses of400mg,200mg and100mg·kg body weight-1·day-1respectively; Enalapril10mg·kg body weight-1·day-1group, themodel group with NS of equal volume. The db/m mice as normal control group wereadministered with NS of equal volume. The administration of each group was performed bygavage daily for a period of8weeks. At the end of the8th weeks, the blood was collectedfrom the eyeball vein to be made in specimens, which is for the purpose of blood biochemicaldetection. Killed the mice, then immediately released the kidney, took the cortex of rightkidney for the observation of renal pathological changes in mice. Storaged the left renal at-80℃, then used RT-PCR to detect the expression of VEGF and PEDF mRNA, meanwhileapplied Western-blotting in the assay of their protein expression.Results: At the end of the experiment, the mice in the model group were in a state ofapathetic, their fur glossy, and they are obviously polydipsia, polyuria, polyphagia; Theirweights、TG、TC、BUN、SCr measured significantly higher than those in normal control group(P<0.01); Renal tissue Masson staining showed that the glomerulus of the mice in the modelgroup were hypertrophy, and their mesangial region widen, their capillary basementmembrane thickened,meanwhile the collagen fibers distributed in floc, under electronmicroscope examination，fusion of foot process, ECM sendiment and disruption of GBM andenlargement of infiltration pores, thickness of GBM, proliferation of mesangial cells andmatrix were observed.The expression of mRNA and VEGF protein in renal tissue of mice inthe model group increased, while the expression of PEDF mRNA and protein reduced,but nochanges mentioned above occured in the normal control group. With8weeks of treatment, compared with model group, the body weight, TG、TC、BUN、SCr of the mice in HPS, highdose and middle dose group, enalapril group decreased significantly (P<0.05); Renalinterstitial fibrosis, the degree of the thickening of the glomerular basement membranereduced (P<0.05); the expression of VEGF mRNA and protein in renal tissue significantlydecreased (P<0.05), while the one of PEDF mRNA and protein increased significantly(P<0.05). The results of correlative analysis showed, there existed a negative linearcorrelation between VEGF and PEDF, and a dose-response relationship between the groups ofHPS, in which the varied indicators of HPS high dose group improved most significantly witha better effect than enalapril group (P<0.05).Conclusion: HPS can treat the early stage of DN in db/db mice. Its mechanism may liein the unique efficacy of rousing of HPS, putting the expression of VEGF and PEDF in thekidneys of DN mice in balance, and further inhibiting the proliferation of renal vascular andretarding the development of glomerular sclerosis and renal interstitial-fibrosis, eventuallycome the function of protecting the kidney.