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糖尿病大鼠肝纤维化组织中MMP-1和TIMP-1的表达变化及意义 被引量:7

The change of expression of MMP-1 and TIMP-1 in hepatic fibrosis rats with diabetes and its significance
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摘要 目的研究MMP-1、TIMP-1在糖尿病大鼠肝纤维化组织的表达变化及意义。方法将SD大鼠随机分为正常对照组(NG组)和实验组,分别以普通饲料和高糖高脂饲料喂养,实验予组链脲佐菌素(STZ)腹腔注射诱导糖尿病大鼠模型。取肝脏组织,行常规HE染色、Masson染色和MMP-1及TIMP-1免疫组化染色并将实验组中肝组织纤维增生者列入糖尿病肝纤维化组(HF组)。于实验开始、STZ诱导2周后和实验结束时检测肝功能(ALT、AST)。结果NG组和HF组大鼠间ALT、AST差异无统计学意义(P>0.05)。HF组大鼠:肝细胞光镜下脂肪变性、细胞水肿、肝窦纤维轻度增生;肝组织TIMP-1表达明显增强,用病理图象分析仪测TIMP-1平均光密度明显高于NG组(P<0.05)且与其胶原纤维表达量呈正相关(r=0.654,P<0.05);而MMP-1平均光密度2组间差异无统计学意义(P>0.05),与Masson染色结果无相关性(P>0.05)。结论TIMP-1表达增高导致的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。 Objective To investigate the change of expression of MMP-1 and TIMP-1 in hepatic fibrosis of diabetic rats and the significance of the changes. Methods Sprague-Dawley rats were randomly divided into normal eonurol group(NG group) fed with regular diet and experiment group fed with high-sugar and high-fat diet. The rats in experiment group were injected with streptozocin(STZ) to induce diabetes. All of the liver specimens were observed by light microscope after HE staining and MASSON specific staining. MMP-1 and TIMP-1 were determined by immunohistochemistroy. Hepatic tissue with fiber hyperplasy was included in diabetic hepatic fibrosis group(HF group). ALT and AST were detected respectively at the beginning and end of the experiment and after STZ was injected for 2 weeks. Results There was no significant difference in the concentrations of serum ALT and AST between NG group and HF group( P 〉 0.05). But some changes could be clearly found in the hepatic tissue of rats in HF group including fatty degeneration, cellularedema, fiber hyperplasy in sinus hepaticus, and much more expression of TIMP-1 was observed in HF group. According to image analysis, the levels of TIMP-1 were significantly higher in HF group than those in NG group ( P 〈 0.05)and so was MMP-1, but there was no significant difference between two groups( P 〉 0.05).There was a positive correlation between the levels of TIMP-1 and collagen( r = 0. 654, P 〈 0.05), but the correlation between the levels of MMP-1 and collagen was not found. Conclusion The disequilibrium of MMP-1/TIMP-1 may play an important role in the occurrence and development of early staGe of diabetic liver fibrosis.
出处 《河北医药》 CAS 2009年第8期901-903,共3页 Hebei Medical Journal
关键词 MMP-1 TIMP-1 糖尿病 肝纤维化 MMP-1 TIMP-1 diabetes hepatic fibrosis
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  • 1Qing He Nie Yong Qian Cheng Yu Mei Xie Yong Xing Zhou Yi Zhan Cao The Center of Infectious Disease Diagnosis and Treatment of PLA,Tangdu Hospital,Forth Military Medical University,Xi’an 710038,Shaanxi Province,ChinaDr,Qing He Nie graduated from Qinghai Medical College as a doctor in 1983,got master degree at Beijing 302 Army Hospital in 1993,got doctor degree at the Third Military Medical University in 1998,engaged in postdoctoral research at the Fourth Military Medical University from 1998 to 2000,now an associate professor,specialized in clinical and experimental research of infectious diseases,had more than 90 papers published,coauthor of ten books,first author of one book..Inhibiting effect of antisense oligonucleotides phosphorthioate on gene expression of TIMP-1 in rat liver fibrosis[J].World Journal of Gastroenterology,2001,7(3):363-369. 被引量:73
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