Relationship Between PDGF-BB/PDGFR-β And The Early Stage Of Liver Fibrosis In Experimental Diabetic Tree Shrews

Objective To study the relationship between PDGF-BB/ PDGFR-βand the early stage of liver fibrosis in experimental diabetic tree shrews.Methods 40 tree shrews were divided randomly into normal controlgroup(groupC, n=8) and streptozocin(STZ)-treated group (n=32).Diabetic animal models were induced by injection of STZ intravenously.Of the STZ-treated group,animals were considered diabetic when fastingblood glucose (FBG) were equal to or more than 11.1 mmol/L (group A,n=13) ,and animals with FBG level less than 11.1 mmol/L were served asSTZ control group (group B, n=9). ALT, AST, Type IV collagen (IV-C) ,Laminin (LN) and Hyaluronic acid (HA) were detected respectivelybefore and after STZ injection 4 and 8 weeks. Liver biopsy wasperformed at the end of the experiment (8 weeks). All of the liverspecimens were observed under light microscope and transmissionelectron microscope. Platelet-derived growth factor BB(PDGF-BB)and platelet-derived growth factor βreceptor(PDGFR-β) weredetected by immunohistochemistry and computer image analysis system.Result There was no significant difference in the concentrations ofserum ALT,AST,IV-C, LN and HA among the three groups in the baselineand 4 or 8 weeks after the experiment. The liver histological damageswere noticed in group A,including hepatocytes swelling , fattydegeneration , glycogen holes in cell nucleus , increased collagen fibrevolume of perisinusoidal areas by Masson trichome. According to imageanalysis , the level of collagen area density was higher in group A thanthat in control group (P<0.05). Besides, the following changes wereobserved under electron microscope,including increased glycogengranules in cytoplasm and nucleus, fatty degeneration, configuration ofmitochondrial illegibility, rough endoplasmic reticulum degranulation,smooth endoplasmic reticulum expansion. The expression of PDGF-BBand PDGFR-βin liver were significantly increased in group Acompared with that of other two groups,and the positive expression ratesof PDGF-BB and PDGFR-βin liver sinusoidal endothelial cell in groupA were higher than that of other two groups. In addition, the levels ofexpression for PDGF-BB and PDGFR-βare positively correlated withthe collagen area density (P<0.01) in group A.Conclusion (1) Early fibrosis of the liver in diabetic tree shrews can befounded by electron microscope and histopathology without significantchange in the concentrations of serum ALT, AST, IV -C , LN and HA .(2)PDGF-BB and PDGFR-βmay play an important role in the developmentand deterioration of liver fibrosis in diabetic tree shrews .(3) PDGF-BBand PDGFR-βmay join the forming of liver sinusoidal endothelial cellcapillarization.