基质金属蛋白酶1/组织金属蛋白酶抑制因子1在常染色体显性遗传性多囊肾组织中的表达

目的:探讨基质金属蛋白酶1(MMP1)/组织金属蛋白酶抑制因子(TIMP1)在正常肾脏、常染色体显性遗传性多囊肾病(ADPKD)肾脏以及肾移植平均(2.5±1.2)年后切除的ADPKD肾组织中的表达差异.方法:用基因表达谱芯片筛选正常肾脏、ADPKD肾脏及肾脏移植后ADPKD肾脏的差异表达基因;以RT-PCR法验证其中差异表达的MMP1/TIMP1.结果:基因芯片筛选发现在正常肾组织与ADPKD肾组织中存在463条差异表达基因,肾移植后ADPKD肾组织对比ADPKD肾组织存在130条差异表达基因.筛选结果表明ADPKD以及肾移植后ADPKD肾脏MMP1/TIMP1表达较正常肾组织明显上调(P＜0.05),而前两者间无显著差异.RT-PCR法证实MMP1/TIMP1在ADPKD肾脏以及肾移植后ADPKD肾组织中的表达均明显上调,明显高于正常肾脏组织(P＜0.05),而前两者间无显著差异.结论:ADPKD的病理改变可能与MMPs/TIMPs基因表达失衡有关,MMPs抑制剂可能会对其有一定的治疗作用.

Expression of matrix metalloproteinases-1/tissue inhibitor of metalloproteinase-1 in kidney of patients with autosomal dominant polycystic kidney disease

Objective: To investigate the differential expression of matrix metalloproteinases-1 / tissue inhibitor of metalloproteinase-1 (MMP-1/TIMP-1) between normal kidney,kidneys of patients with autosomal dominant polycystic kidney disease(ADPKD),and the original kidneys after renal transplantation(OKRT).Methods: DNA microarray technique was used to analyze the differential gene expression in the above 3 tissues.Semi-quantitive RT-PCR was performed to verify the differentially expressed genes.Results: There were 463 differentially expressed genes between normal kidney and ADPKD tissues and 130 differentially expressed genes between ADPKD and the OKRT tissues.Expression of MMP1/TIMP1 in the ADPKD and the OKRT tissues were significantly higher than that in the normal kidney tissue(P<0.05),with no significant difference found between the former 2 groups.Results of RT-PCR were consistent with the microarray findings.Conclusion: The pathogenesis of(ADPKD) may be related with the high expression of MMPs/TIMPs and the inhibitor of MMPs may have therapeutic effect on ADPKD.