【作者】 周嘉；

【导师】 洗苏； 罗佐杰； 秦映芬； 陈青云；

【作者基本信息】 广西医科大学 ， 内科内分泌， 2003， 硕士

【摘要】 目的 研究MMP-1/TIMP-1与糖尿病树鼩早期肝纤维化的关系。方法 将40只树鼩随机分到正常对照组（8只）和链脲佐菌素（STZ）处理组（32只），静脉注射STZ诱导树鼩糖尿病模型，将成模的树鼩归为糖尿病组（13只）， 未成模的树鼩归为STZ对照组（9只）。于注药前和成模后4、8周分别行血生化检查（ALT、AST）和放免检查（Ⅳ·C、LN、HA）。成模后8周对3组树鼩肝组织活检行常规HE染色、PAS、D-PAS染色、Masson染色和MMP-1/TIMP-1免疫组化染色，电镜观察肝脏超微结构。结果 3组树鼩间ALT、AST、Ⅳ·C、LN、HA无明显差别（P>0.05）。糖尿病组树鼩肝细胞光镜和电镜下胞浆糖原明显增多、核内糖原空洞、脂肪变性、细胞水肿、肝窦纤维增生、线粒体结构模糊，粗面内质网脱粒，滑面内质网扩张。糖尿病组肝组织MMP-1/TIMP-1表达的阳性均较其余两组强，其中用病理图象分析仪测MMP-1平均光密度与其余两组无统计学差异，与Masson染色结果无相关性（P﹥0.05）；TIMP-1平均光密度明显高于两组对照组（P﹤0.01）且与Masson染色结果显著相关性（r=0.676，P﹤0.05）。<WP=4>结论1. 糖尿病树鼩成模8周在电镜下观察到早期肝纤维化的表现2. 糖尿病树鼩在电镜下观察到早期肝纤维化时，肝功能和Ⅳ·C、HA、LN无明显变化3. 糖尿病树鼩早期肝纤维化中MMP-1表达无明显改变，而TIMP-1表达显著增高，且与胶原纤维表达量增高呈显著相关，提示MMP-1/TIMP-1系统失衡在糖尿病早期肝纤维化的发生、发展中有重要作用。更多还原

【Abstract】 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 :<WP=6>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 .更多还原