Effects Of The Giant Knotweed Rhizome Medicine In The Expression Of RAGE And VEGF Of Diabetic Nephropathy

Objective:To observe the effects of giant knotweed rhizome medicine on FPG,TC,TG,CCR,24hUP and on the pathological changes and expression of Receptor for advanced glycation end products(RAGE),Vascular endothelial growth factor(VEGF) in nephridial tissue in experimental diabetic rat,and to discuss its Reno-protective mechanisms.Methods:J36 healthy male Whister rats with body weight from 130gram to 150 gram were randomly divided into two groups.8 rats were selected as control group fed with common food(nomal group).Other 28 rats were given with the diets enriched with sucrose(20%w/w)and lard(10%w/w)and cholesterol(2.5%w/w)and cholic acid(0.5% w/w).After 4 weeks these rats were induced to Diabetic rat models with FBG≥16.7mmol /L and urine glucose+++～++++by injection of streptozotocin(STZ)into vena caudalis. then they were randomly divided into 3 groups:modal group treated with distilled water (n=9),giant knotweed rhizome medicine group(1.5g/kg,n=9),and fluvastatin group (7mg/kg,n=8).All rats were not treated with insulin or other anti-diabetes drugs in experimental procedures.FPG,KW/BW(kidney weigt/body weigh),creatinine clearance (Ccr),24h urinary protein(24hUP)etc,were observed after 8 weeks.The pathological change of kidney were observed by using light and electron microscopy.The expression of receptor for advanced glycation end products(RAGE)and vascular endothelial growth factor(VEGF)in glomcrulus was detected by using immune histochemical methods. Results:(1)biochemical indicator:After interfering,compared with the nomal group,the levels of FPG,TC,TG,Ccr,24hUP,KW/BW in the other three groups were increased more significantly(P＜0.01,P＜0.05);the levels of Ccr,24hUP,KW/BW in giant knotweed rhizome medicine group and fluvastatin group were decreased more significantly than modal groups(P＜0.01,P＜0.05),and FPG was also decreased which was no signifycant differences;the levels of TC,TG in fluvastatin group were decreased more significantly than modal group(P＜0.05).(2)By optical and electron microscope,there are copious RER and chondrosomes in podocytes who has ladge volume,slender foot process,nomal BMT and complete constit in nomal group,compared with the nomal group,BM in the other three groups whose mesenterium matrix increased,foot process confluenced,and cell organ decreased were more thick(P＜0.01) and GV of those were ladger(P＜0.01);compared with the modal group,BM were thinner and GV were smaller in giant knotweed rhizome medicine group and fluvastatin group.(3)RAGE and VEGF expressed in cellular membrane.Expressions of RAGE,VEGF were weakly expressed in renal corpuscle endothelial cell in nomal group;the continuous expressions of RAGE,VEGF were significantly increased in renal corpuscle endothelial cell and mesangial region in model group(p＜0.01).The expressions of RAGE,VEGF in giant knotweed rhizome medicine group and fluvastatin group were stronger than those in nomal group(P＜0.01),but weaker than those in modal group(P＜0.01,P＜0.05)(4)The correlation analysis showed that there was significant positive correlation between 24hUP and the expression of RAGE,the expression of VEGF,BMT.(r=0.776, P＜0.05;r=0.799,P＜0.01;r=0.800,P＜0.01);the expression of VEGF and RAGE have positive correlation(r=0.743,P＜0.05).Conelusion:(1)the upregulation of RAGE,VEGF is one of pathomechanisms of DN, and the interaction of RAGE,VEGF accelerate development of DN,according to the expression of RAGE,VEGF.(2)giant knotweed rhizome medicine have been demonstrated to inhibit BM from thickening,downregulate the expression of RAGE,VEGF,reduce CCR and excretion of albuminuria of DN in early stage and delay the progression of glomerular sclerosis,whose renoprotective effects mechanism may be at least related with down-regulating the expression of RAGE,VEGF in nephridial tissueofdiabetic rats.(3)giant knotweed rhizome medicine may decrease FPG,which need to be improved.It have no effect to blood fat.(4)fluvastatin have been demonstrated to upregulate DM the expression of RAGE,VEGF nephridial tissue,reduce the excretion of albuminuria,its renoprotection mechanism rely on decreasing blood fat and upregulating the expression of RAGE,VEGF which still need study,fluvastatin is sure benefit to DN.