Relationship Between MMP-1/TIMP-1 And The Early Stage Of Liver Fibrosis In Diabetic Tree Shrews

Objective To study the relationship between MMP-1/TIMP-1 and the early stage of liver fibrosis in diabetic tree shrews. Methods 40 tree shrews were divided randomly into normal control group (n=8) and treatment group (n=32). The treatment group were injected of vein with streptozocin (STZ) to induce diabetes. Eight weeks later , the tree shrews maintained fasting blood glucose (FBG) at level of ≥11.1mmol/Lwere divided into diabetes group (n=13), and those maintained FBG<11.1mmol/Linto STZ control group (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 after the 8th week of the experiment. All of the liver specimens were observed with light microscope and electron microscope. MMP-1 and TIMP-1were studied by immunohistochemistroy and computer image analysis. Result There was no significant difference in the concentrations of serum ALT , AST , Ⅳ·C , LN and HA among the three groups before and after 4 , 8 weeks. The liver histological damages were observed in diabetes group, including hepatocytes swelling , some having fatty degeneration , glycogen holes in cell nuclear , the collagen of perisinusoidal areas increasing by Masson trichome. According to image analysis , the level of Masson trichome was higher in diabetes group than that of in control group (P<0.05) . And the following changes were observed under electron microscope :glycogen granules in cytoplasm and nuclear increasing , fatty degeneration , configuration of mitochondrial illegibility , rough endoplasmic reticulum degranulation, smooth endoplasmic reticulum expansion . The early stage of liver fibrosis was observed in portal areas. Increase expression of MMP-1 , TIMP-1 was related to the early stage of liver fibrosis . According to image analysis , the level of TIMP-1 was higher in diabetes group than that of the other groups (P<0.01) and so did of MMP-1 but there was no significant difference among three groups (P>0.05) . There was a positive correlation between the level of TIMP-1 and collagen (r=0.676 ,P<0.05) . The correlation between the level of MMP-1 and collagen was not found . Conclusion 1. There is the early stage of liver fibrosis in diabetic tree shrews with electron microscope . 2. There is no significant change in the concentrations of serum ALT , AST , Ⅳ·C , LN and HA on the early stage of diabetic liver fibrosis . 3. MMP-1/TIMP-1 may play a important role influencing the development of early stage of liver fibrosis in diabetes .