TIMP-1、MCP-1在5/6肾切除模型大鼠中表达的研究

The expression of TIMP-1 and MCP-1 in 5/6 nephrectomy rats

目的 通过观察5/6肾切除大鼠模型中金属蛋白酶组织抑制因子-1（TIMP-1）、单核细胞趋化因子蛋白-1（MCP-1）与肾纤维化的关系,探讨TIMP-1、MCP-1作为肾纤维化早期生物学标志的可行性. 方法 将清洁级雄性大鼠随机分成对照组和模型组. 对照组只剥离肾包膜,不切除肾实质,模型组建立5/6肾切除大鼠模型. 应用酶联免疫吸附试验检测血清中透明质酸、层粘连蛋白、Ⅲ型胶原、Ⅳ型胶原等的表达水平,应用荧光定量 PCR 方法检测两组大鼠肾组织中 MCP-1、TIMP-1 mRNA的表达水平,结合肾病理改变及血肌酐、尿素氮等的水平,评估MCP-1、TIMP-1在肾纤维化中的意义. 结果 造模成功后,模型组肾小球积分、肾间质积分、血肌酐、尿素氮均高于对照组,差异有统计学意义（P〈0.05）;模型组大鼠造模成功后4、8、12周时,大鼠肾组织中MCP-1的表达逐渐升高,TIMP-1的表达逐渐降低,二者表达水平符合早期肾纤维化进展进程. 结论 大鼠肾组织中MCP-1、TIMP-1的表达与肾纤维化病理改变一致,可作为早期肾纤维化潜在的生物学标志.

Objective Through observing tissue metalloproteinase inhibitor-1 （TIMP-1）,mono-cyte chemoattractant protein-1 （MCP-1）expression of the 5/6 nephrectomy rat,and observing the relation-ship between TIMP-1 and MCP-1 with renal fibrosis,to find the probability of TIMP-1 and MCP-1 as bio-markers in early renal fibrosis.Methods The clean grade male rats were randomly divided into the model group and the control group.The rats in the control group were only stripped the renal capsule,without re-section of renal parenchyma,the others in the model group were established to be 5/6 renal failure models. Using enzyme-linked immunosorbent assay（ELISA）to detect the expression level of serum hyaluronic acid, laminin,egg white type Ⅲ collagen,type Ⅳ collagen,and using the fluorescent quantitative PCR to detect the expression level of MCP-1 and TIMP-1 mRNA in kidney tissue of two groups of rats,combined with re-nal pathological changes and serum creatinine and urea nitrogen levels,assessing the significance of MCP-1,TIMP-1 in renal fibrosis.Results After the modeling,the glomerular score,renal interstitial score,serum creatinine and blood urea nitrogen in the model group were higher than those in the control group,and the difference was statistically significant （P ＆lt;0.05）;after the modeling of 4,8and12 weeks in the model group,the expression of MCP-1 in renal tissue was gradually elevated,the expression of TIMP-1 was gradu-ally reduced,and the expression level born a strong resemblance with the early renal fibrosis process.Con-clusion The expression level of the MCP-1 and TIMP-1 born a strong resemblance with the early renal fi-brosis,it can be used as a potential biomarker for early renal fibrosis.