Relationship Between The Activation Of Hepatic Stellate Cell And The Early Stage Of Liver Fibrosis In Experimental Diabetic Tree Shrews

Objective To study the relationship between the activation of hepatic stellate cell(HSC) and the early stage of liver fibrosis in experimental diabetic tree shrews. Methods 40 tree shrews were divided randomly into normal control group (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 fasting blood 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 as STZ control group (group B, n=9).ALT, AST,Type Ⅳ collagen (Ⅳ-C) , Laminin (LN) and Hyaluronic acid (HA) were detected respectively before and after STZ injection 4 and 8 weeks. Liver biopsy was performed at the end of the experiment (8 weeks). All of the liver specimens were observed under light microscope and transmission electron microscope. α-smooth muscle actin(α-SMA) and connective tissue growth factor (CTGF) were detected by immunohistochemistry and computer image analysis system.Result There was no significant difference in the concentrations of serum ALT, AST,Ⅳ-C , LN and HA among the three groups in the baseline and 4 or 8 weeks after the experiment. The liver histological damages were noticed in group A, including hepatocytes swelling , fatty degeneration , glycogen holes in cell nucleus , increased collagen fibre volume of perisinusoidal areas by Masson trichome. According to image analysis , The level of collagen area density was higher in group A than that in group C (P<0.05) . Besides, the following changes were noticed under electron microscope,including increased glycogen granules in cytoplasm and nucleus, fatty degeneration , configuration of mitochondrial illegibility , rough endoplasmic reticulum degranulation, smooth endoplasmic reticulum expansion. The expression of α-SMA and CTGF in liver were significantly increased in group A compared with that of other two groups. There were some α-SMA positive HSCs, namely, activated HSCs in the liver of group A.In addition, the level of expression for α-SMA is positively correlated with the collagen area density (r=0.791 ,P<0.01) in group A.Conclusion ⑴ Early fibrosis of the liver in diabetic tree shrews can be founded by electron microscope and histopathology without significant change in the concentrations of serum ALT , AST , Ⅳ-C , LN and HA .⑵ HSC may play an important role in the development and deterioration of liver fibrosis in diabetic tree shrews .(3)Expresion of CTGF is increased in vascular endothelial cell of diabetic tree shrews liver and it cannot be detected in HSC ,so there is not possibly close relation between CTGF and the early stage of liver fibrosis in diabetic tree shrews model.