The Change And The Mechanism Of The Hepatic Cirrhosis In Rats Which Are Injected Vascular Endothelial Growth Factor

Objective:Used rat models of portal hypertension established by Thioacetamide (TAA) administration ,we inject the VEGF- D into the portal vein ,observing the change of the liver super microstructural after gene transfection, further clarifying the mechanism that VEGF cause to a lower portal pressure and that VEGF cause the change of super microstructural of liver through the angiogenesis gene array.Method:50 rats were divided into two groups,model groups(40) and control groups(10). The model groups accepted 0.03% TAA administration, after 5 weeks , the concentration of TAA changed to 0.04% .Induced 10 weeks the portal hypertension models would be built.Determined the pressure of superior mesenteric vein and obtain cirrhosis liver example, then infused PCHO/hVEGF 150μg through superior mesenteric vein.After 3 weeks,determined the pressure of superior mesenteric vein again,then sacrificed all rats, took the liver organization specimen.The expression of VEGF in protein level were identified. The change of the liver super microstructural after gene transfection was observed by electronic microscope.Taking the liver organization to go the gene chip experiment,detected the change of Angiogenesis Gene after gene transfection.ResultrAfter VEGF transfection, accompanied with the VEGF protein expression increment, the pressure of portal vein decreased. The reduilts of electronic microscope showed thepatic sinusoidcapillarization performed an important actor in the happen of portal hypertension. The fenestra of endothelial cell in hepatic sinusoid reduced and the diameter of fenestra decreased. The formation of basement membrane impaired the substance exchange between blood and hepatic cells. Oxygen deficiency, metabolic product accumulation ,cell necrosis, were the basic pathologic physiology change.The VEGF transfection promoted endothelial cell in hepatic sinusoid growth,the number of fenestra and diameter increased notablely. The basement membrane degradation promoted the substance exchange between blood and hepatic cells, so the liver cell regenerated, the portal vein pressure decreased.The VEGF transfection promoted endothelial cell in hepatic sinusoid growth and the basement membrane degradation through many growth factors interaction. Mainly include: Vascular Endothelial Growth Factors & Receptors: Figf( VEGFD), Pgf, Vegf, Vegfb, Vegfc; Ephrin Family Members: Efna2( the Ephrin A2), Efnb2( the Ephrin B2), Ephb4( the Ephrin B4); Fibroblast Growth Factors & Receptors: Fgfl( aFGF), Fgf6 /Fgfr3 ; Platelet-derived Growth Factors & Receptors:The Pdgfa, Pdgfb/Pdgfrb, Transforming Growth Factors & Receptors: Tgfbl, Tgfb2, Tgfb3 / Tgfbr2; Other Growth Factors: Ctgf, Egf, Igfl, Grol. Chemokines:Nrp( neuropilin).