【作者】 班丽；

【导师】 顾霞；

【作者基本信息】 新疆医科大学 ， 病理学， 2007， 硕士

【摘要】 目的:研究转化生长因子TGF-β1和基质金属蛋白酶MMP-2及其抑制剂TIMP-1在不同程度肾纤维化组织中的表达,探讨肾纤维化发生、进展的分子病理学机制及在治疗中的指导意义。方法:对21例肾移植后,因移植肾功能进行性减退,再次行移植肾切除手术,切除的移植肾标本及10例正常肾组织进行HE染色,根据移植肾纤维化程度和Banff病理标准进行分期和TGF-β1、MMP-2、TIMP-1蛋白免疫组化染色,对免疫组化染色结果,应用体视学技术作图像定量分析;同时检测患者血肌酐(Cr)和尿素氮(BUN)的水平;并分析TGF-β1、MMP-2、TIMP-1蛋白表达和血肌酐(Cr)和尿素氮(BUN)的水平与移植肾纤维化程度的关系。结果:在轻度肾间质纤维化(1期),肾组织中TGF-β1、MMP-2、TIMP-1免疫染色阳性强度均较正常肾组织(0期)明显增加;随着纤维化进展(2期、3期),TGF-β1、TIMP-1阳性表达强度逐渐增加,纤维化各期与正常组之间差异有统计学意义ρ＜0.01;MMP-2蛋白表达随着移植肾纤维化程度加重而逐渐降低,纤维化各期与正常组之间及纤维化1期与2、3期之间,差异有统计学意义ρ＜0.01:TGF-β1、TIMP-1二者在纤维化肾组织中的表达呈正相关性。MMP-2、TIMP-1二者在纤维化肾组织中的表达呈负相关性。随着移植肾纤维化程度的加重,血清肌酐(Cr)和尿素氮(BUN)的平均水平逐渐升高。结论:TGF-β1、MMP-2、TIMP-1参与了肾纤维化的发生、发展,提示TGF-β1表达量增高及TIMP-1的活性增加可能是促进细胞外基质积聚形成纤维化的重要条件,而MMP-2则抑制其进展。检测三者的表达与血清肌酐(Cr)和尿素氮(BUN)水平,可以做为临床判断肾纤维化程度的辅助指标。更多还原

【Abstract】 Objective:To dectect the protein expression of TGF-β1,MMP-2 and TIMP-1 and to study the molecular pathological mechanism of renal fibrosis and its significance for treament in the Chronic allograft nephropathy(CAN) with fibrosis.Methods:21 cases kidney specimens were collected from patients with CAN and 10 normal kidney specimens of non-nephropathy patients.HE and immunohistochemical staining were performed to detect pathological stage according to Banff pathological standard for renal fibrosis and protain expression of TGF-β1,MMP-2 and TIMP-1.An image quantitative assessment was carried out by stereological to analysis expression of TGF-β1,MMP-2 and TIMP-1.At the same time serum creatinine(Cr) and urea nitrogen(BUN) were detected.. Results:In the early staging of renal fibrosis(1 stage) positive expression of TGF-β1、MMP-2、TIMP-1 were revealed stronger than normal kidney tiassues(0 stage).With renal fibrosis increasing,expression of TGF-β1 and TIMP-1 protain were revealed a increasing gradually positive staining,and there are significant difference between the fibrosis groups and normal one(p＜0.01).Positive staining of MMP-2 was gradual weak and low even negative.There are significant difference between fibrosis groups and normal one for MMP-2 expression(p＜0.01).It showed that there was positive correlation between expression of TGF-β1 and TIMP-1 and negative correlation between expression MMP-2 and TIMP-1 and no correlation between TGF-β1 and MMP-2.With renal fibrosis progressing,the level of serum creatinine(Cr) and urea nitrogen(BUN) were higher by degree.Conclusions:It suggested that TGF-β1,MMP-2 and TIMP-1 maybe participated in the genesis and development of renal fibrosis.Higher bioactivity of TGF-β1、TIMP-1 may be important factors in renal fibrosis,and function of MMP-2 was reverse to TGF-β1、TIMP-1.It is valuable o detect TGF-β1、MMP-2、TIMP-1 and the level of serum creatinine(Cr) and urea nitrogen(BUN) for judgement stage of renal fibrosis更多还原