摘要
目的:动态观察骨调素(OPN)在链脲佐菌素(STZ)诱导的糖尿病大鼠肾小管的表达,探讨它与p38丝裂原活化蛋白激酶(p38MAPK)、核转录因子-κB(NF-κB)及肾损害之间的关系。方法:雄性SD大鼠,注射STZ诱导糖尿病(DM),随机分成5组,每组分别设鼠龄匹配的正常对照组。免疫组化方法检测肾小管OPN、p38MAPK、NF-κB及纤连蛋白(FN)的表达;Western印迹法检测肾皮质OPN和p38MAPK蛋白质水平;生化方法测定血糖、血肌酐及24h尿蛋白量;光镜检查肾组织的形态改变。结果:Western印迹和免疫组化检测发现糖尿病3d大鼠肾组织p38MAPK和DM7dOPN的表达增多,并随病程发展而增加,与正常对照组比较有显著差异(P<0.01)。DM4周,肾小管OPN的表达与p38MAPK、NF-κB、FN表达及蛋白尿呈显著正相关。结论:糖尿病大鼠肾小管OPN表达增加参与了糖尿病肾小管间质损害的发病机制;肾小管p38MAPK可能介导了DM状态时NF-κB的表达,进而调节OPN的表达增多。
AIM： To observe dynamically osteopontin （OPN） expression in renal tubules of streptozotocin （STZ） - induced diabetic rats, and to explore the relationship between OPN and p38MAPK, nuclear transcription factor - kB （NF- kB）, and renal injures. METHODS ： Male SD rats were injected with STZ to induce diabetes mellitus（ DM）, which were divided into 5 groups randomly, and meanwhile there were other 5 age - matched normal control groups. Immu- nohistochemistry was employed to observe the expression of OPN, p38MAPK, NF- kB and fibronectin （FN） in renal tubules. The OPN and p38MAPK proteins in renal cortex were detected by Western blotting. Blood glucose, serum creatinine and 24 h urine protein were examined by biochemistry methods. The renal morphology was checked through light microscopy. RESULTS： The immunohistochemistry and Western blotting results showed that the expression of p38MAPK 3 days after DM and OPN 7 days after DM in renal cortex or tubules were increased significantly compared with control groups （P 〈 0. 01 ）, and were further increased following the course of diabetes. In DM week g, there were positive correlations between OPN and p38MAPK, NF - kB, FN, and 24 h urine protein. CONCLUSION： Our results suggest that an increase in OPN expression in renal tubules participates in the injury mechanisms of renal tubulo - intestitium in diabetic rats. The increased expression of p38MAPK may induce NF- kB expression in the tubules under DM condition, and then NF -kB promotes the expression of OPN.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2007年第3期559-562,共4页
Chinese Journal of Pathophysiology
基金
贵州省高层次人才特助经费资助项目(No20040517)
贵州省省长基金资助项目(No2005-303)
