Protection Of Fufang Xueshuantong Against Diabetic Microangiopathy Of Rats And Approaching The Potential Mechanisms

Diabete is a lifelong disease characterized by high glucose resulting from glucose metabolic disorder.WHO estimated that worldwide more than 170 millions of people afflicted by this chronic disease,and this number will increase to 360millions in 2030.Diabetic nephropathy(DN) and diabetic retinopathy(DR) are common diabetic systemic microangiopathy.Both disease get worse with diabetes duration. DR and DN are common reason of adult blindness and end-stage renal disease in western countries.DN and DR show common pathological characteristics underlying microcirculation, microangioma and capillary basement membrane thickening. The pathogenetic sequence is initiated by a series of interrelated biochemical abnormalities associated with hyperglycemia toxicity, activation of polyol pathway,hexosamine pathway,protein kinase C and oxidative stress, rennin-angiotensinal dosterone system and some growth factor.There are many research have shown that antioxidant a-lipoic acid, ARB losartan can improve the oxidative stress,local RAS blocked to improve diabetic microangiopathy.This study used a variety of research tools on injuries of retina and kidney in DN and DR,the damage of oxidative stress and cell factor,changes of tissue ultrastructure.And the use of fufang xueshuantong, a-lipoic acid,losartan on the intervention of DN and DR study, we find that fufang xueshuantong have protect effection of DR and DN. Thus we investigate the potential mechanism of oxidative stress, angiotensinⅡ, ultrastructure, PEDF mRNA.Study aim:Investigating the protect effection of DN and DR and the potential mechanism.Study object and methods:Male SD rats have been studied. Diabetic rats have been induced by intraperitoneal injection of streptozotocin(DM model).Control group(NG group) n=20; diabetic rats (n=80),divided into untreated group(DM group),fufang xueshuantong treated group (XST group), a-lipoic acid treated group(LXS group),losartan treated group,20 rats each group.Reseach is divided into three parts: PartⅠ:detection blood glucose,lipid, serum creatinine, urea nitrogen,weigh, left kidney weigh,24 h urine protein,determination of oxidation products in renal cortex of SOD,MDA,GSH-Px levels, detection iNOS mRNA of renal cortex by RT-PCR, electron microscopic observation of ultrastructural changes of glomerular, investigat whether fufang xueshuantong have protection of diabetic nephropathy and potential mechanism.PartⅡ:determination of oxidation products of blood,detection PEDF mRNA of retina by RT-PCR,microscopic observation of ultrastructural changes of retinal basement membrane and pericytes.PartⅢ:detection angiotensin II in blood after treatment for 2 weeks and 12weeks, compare it in DM group, LST group, NG group, XST group.Evaluation the effection of fufangxueshuantong against RAAS.Result:After 12 weeks,compared with NG group,rats in DM group had a higher 24 hour-urinary and KW/BW(P<0.05), and those in XST group and LXS group are lower compared with DM group(P<0.05). compared with NG group,rats in DM group had a higher KW/BW(P<0.05), and those in XST group and LXS group are lower compared with DM group,especially in XST group(P<0.05). Electron microscopic results show that the mesangial cells and endothelial cells in DM group were swollen and had fusion/ disappearance of podocytic process, increased mesenteric matrix, uneven basal membrane,but the above changes were improved in XST and LXS group.Compared with NG group,MDA increased(P<0.05),GSH-Px lowered(P<0.01)in DM group,all the changes were improved in XST and LXS group(MDA:XST group p<0.05;GSH-Px both group p<0.01). The expression of iNOS mRNA in DM group increased compared with NG group (P<0.05), after treated with drugs,the level is increased.The distinct between DM group and XST group is Statistically significant.Compared with NG,SOD activity and MDA level of DM group are increased,after both drug treated,they decreased(P<0.05)。Low positive expression of PEDF mRNA (P<0.005)。The expression of PEDF mRNA in XST group increased compared with DM group (P<0.05). Electron mi croscopic results showed that thickness of Retinal basement membrane is increased, Endothelial cell swellings and shows finger-like protuberances, mitochondrion swellings even Mitochondrial vacuolization.The drugs improve all the changes above.Compared with NG, level of AngⅡin DM is increased (P<0.01).After treatment of fufang xueshuantong and losartan, the level is decreased (P<0.01).Conclusion:In this study, a recognized anti-oxidant a-lipoic acid as control, observe the effect of fufang xueshuantong against diabetic nephropathy, result show that, compared with DM group,fufangxueshuantong could decrease the level of 24 h albumin excretion, kidney hypertrophy factor (left kidney weigh/body weigh), improve structure of GBM, have a protect effection of diabetic kidney via improving the antioxidant capacity of kidney.Fufang xueshuantong may protect diabetic retinopathy via antioxidant, increase expression of PEDF.After treatment of fufang xueshuantong and losartan, the level of angiotensinⅡ, the difference between them have no statistically significant. Fufangxueshuantong may have protection of diabetic microangiopathy by increasing level of angiotensinⅡ.