摘要
目的 探讨金属蛋白酶组织抑制剂 1(TIMP 1)参与肾小管间质损害的机制及防治措施。方法 分 3组通过输尿管逆行注射将等体积生理盐水、空载体、反义TIMP 1基因全长逆转录病毒载体分别导入单侧输尿管梗阻大鼠的肾脏 ,检测肾外源基因的表达 ,观察肾小管间质损害的变化。结果 反义TIMP 1基因可以在单侧输尿管梗阻大鼠肾小管间质细胞表达。反义TIMP 1组单侧输尿管梗阻术后较盐水组和空载体组大鼠梗阻肾组织内TIMP 1蛋白质表达明显减少 (3d :0 75± 0 0 7vs1 18± 0 12、1 14± 0 14 ,P <0 0 5 ;7d :2 0 2± 0 16vs 4 0 7± 0 5 7、4 13± 0 6 0 ,P <0 0 1)。免疫组化显示反义TIMP 1组肾小管间质的增殖细胞核抗原和α 平滑肌肌动蛋白抗原表达下调。与两对照组相比 ,反义TIMP 1组肾间质相对面积明显下降 (3d :6 0± 0 7vs8 2± 1 2、8 2± 1 3,P <0 0 1;7d :16 2±1 1vs 2 1 2± 2 6、2 1 0± 2 4 ,P <0 0 1)。结论 反义TIMP 1可能通过抑制肾间质TIMP
Objective To observe the effect of antisense human tissue inhibitor of metalloproteinase 1 (hTIMP 1) on tubulointerstitial lesion induced by unilateral wreteral obstruction(UUO) Methods Forty two SD rats, divided into 3 groups equally, underwent UUO and received intra ureteral injection of normal salin, empty retroviral vectors and recombinant retroviral vectors containing antisense hTIMP 1 respectively, and were sacrificed 3 and 7 days after the operation The expression of antisense h TIMP 1 in rat kidney was detectdd by RT PCR Immunohistochemistry was used to detect the expression of rat TIMP 1, α SMA actin (α SMA), and proliferating cell nucleus antigen (PCNA) in tubulointerstitium The relative area of renal tubulointerstitium was calculated Results The expression of antisense hTIMP 1 mRNA was detected in rat renal tubulointerstitum The expressions of rat TIMP 1, α SMA and PCNA were lower in the obstructed kidneys of rats treated with antisense hTIMP 1 than those in the rats in empty vectors group and normal saline group (3 day after :0 75±0 07 vs 1 18±0 12, 1 14± 0 14, P <0 05;7 days after:2 02±0 16 vs 4 07±0 57, 4 13±0 60, P <0 01) The relative area of renal tubulointerstitium in rats treated with antisense hTIMP 1 was smaller than those in the empty vetors group and normal saline group (3 days after:6 0±0 7 vs 8 2±1 2, 8 2±1 3, P <0 01;7 days after:16 2±1 0 vs 21 2± 2 6, 21 0±2 4, P <0 01) More renal tubules were dilated, infiltration of imflammatory cells was seen focally or diffusely, and the relative area of renal tubulointerstitium was smaller in the antisense hTIMP 1 group than in the empty vectors group and normal saline group No difference was seen among the degrees of dilation /atrophy of renal tubules and infiltration of inflammatory cells in the three groups No differdnce was seen between the relative area of renal tubulointerstitium in empty vectors group and normal saline group Conclusion Antisense hTIMP 1 may have benefifial effects on the tubulointerstitial lesion of obstructive nephropathy through inhibiting the expression of TIMP 1 in tubulointerstitum and the proliferation of interstitial and tubular cells
出处
《中华医学杂志》
CAS
CSCD
北大核心
2002年第9期617-621,共5页
National Medical Journal of China
基金
国家自然科学基金资助项目 (3 0 0 0 0 0 80 )
国家 973重点基础研究发展规划基金资助项目 (G2 0 0 0 0 5 70 0 3 )
