The Effect Of HVEGF165 Gene Transfection To Pancreatic Islets On The Revascularization And Function Of Engrafted Inbred Rats' Islets Posttransplantation

Pancreatic islet transplantation has been verified successful in the treatment for type 1 diabetes clinically. However, a high number of islets are required to establish euglycemia, which results from such factors as allo-immunological rejecting reaction and primary nonfunction of islets (PNF). The apoptosis of islets' β cells, nonspecific inflammatory response, " Anoikis " , ischemia and hypoxia are related to PNF.Islets of Langerhans isolated from pancreas are avascular because the vasculature around and inside islets are completely disrupted during the digestion with collagenase. Engrafted islets have to reconstruct the vasculature, i.e. revascularization to ensure adequate survival. However the vascular density and oxygen tension in transplanted islets are markedly decreased compared with endogenous islets even when the revascularization of engrafted islets has completed. To promote the revascularization so as to improve the microcirculation of transplanted islets deserve to be researched.Vascular endothelial growth factor (VEGF) is a specific endothelial cell mitogen and a strong vascular permeability factor (VPF). VEGF also plays an important role in the development of embryonic pancreatic endocrinic tissue. It's worthy of researching whether islets overexpressing VEGF could result in better revascularization and stronger biological function after transplantation.Objectives : To research the effect of transfecting the hVEGF165 gene on the revascularization and function of syngenic pancreatic islets posttransplantation. Methods : The recombinant replication-deficient adenovirus vector named AdhVEGF165 was constructed, which carried the hVEGF165 gene. Freshly isolated islets of SD rats were tansfected with AdhVEGF165 in vitro. The expression of hVEGF165 was determined with ELISA Kit in vitro and with Miles trial in vivo. Finally the transfected islets of inbred Lewis rats were transplanted into the liver of syngenic diabetic rat via portal vein. The recipient rats were divided into three guoups according to different disposal to donors' islets, i.e. group VEGF, islets were transfected with AdhVEGF165; control group GFP, with AdGFP; and control group...