摘要
目的:观察糖尿病大鼠肾小管p38丝裂原活化蛋白激酶(p38MAPK)、NF-κB、I-κB、P选择素和MCP-1表达的动态变化,探讨相互间关系及在糖尿病性肾病(DN)发生发展中的作用。方法:链佐星(链脲佐菌素)诱导大鼠糖尿病,并随机分为3 d、1周、2周、4周和8周组,每组设鼠龄匹配的正常对照组。免疫组化法检测肾小管P选择素、MCP-1、p38MAPK、NF-κB和纤连蛋白(FN);Western印迹测肾皮质I-κB和p38MAPK蛋白;PAS染色,光镜观察肾组织形态;生化法测血糖和尿蛋白。结果:糖尿病3 d组可见肾脏指数大于正常组,出现蛋白尿。糖尿病1周组肾小管p38MAPK、NF-κB、P选择素和MCP-1表达明显增加,糖尿病2周组肾小管间质FN阳性表达增加,并且都随着糖尿病病程发展而增加,而肾皮质I-κB蛋白从糖尿病1周开始逐渐减少。糖尿病4周,P选择素和MCP-1表达十分显著,并且与p38MAPK、NF-κB、FN、蛋白尿及肾脏指数呈正相关。结论:p38MAPK和NF-κB可能介导了糖尿病大鼠肾小管P选择素和MCP-1表达上调,并参与DN肾小管-间质病变的发病机制。
Objective：To explore the dynamic expression of P-selectin, MCP-1, NF-KB and p38MAPK in the renal tubules of diabetic rats and to investigate their mutual relationship and roles in the patbogenesis of diabetic nepbropatby. Methods ： Streptozotozin （STZ） -induced diabetic rats were randomly divided into day 3, week 1, week 2, week 4 and week 8 groups, each group having a normal age-matched control group. Immunobistocbemistry was employed to detect the expression of P-selectin, MCP-1, NF-KB, p38MAPK and fibronectin（FN） in the renal tubules, p38MAPK and I-KB proteins in the renal cortex were detected by Western blot methods. The morphological changes of renal tissues were observed under light microscopy in PAS staining sections. Blood glucose and 24 hours urine proteins were analyzed by biochemistry methods. Results： Increased renal index and urine proteins were observed from diabetes day 3. The expression of p38MAPK, NF-KB ,P-selectin and MCP-1 in renal tubules were increased in diabetes day 3 and week 1 growes compared with those of the normal age-matched control group （ P 〈 0. 05 ） respectively, and thereafter the increase was more significant with development of diabetes while I-KB protein decreased. The expression of FN in renal tubules of diabetic groups was increased compared with that of the normal control group from week 2 （ P 〈 0. 05 ）. In diabetes week 4group, the expression of P-selectin and MCP-1 was quite remarkable, and was positively correlated with p38MAPK, NF-KB and FN expression and renal index（ P 〈0.05 ）. Conclusion：P38MAPK and NF-KB may up-regulate the expression of P-selectin and MCP-1 in the renal tubules of diabetic rats, which play an important role in the pathogenesis of the diabetic tubulo-interstitium injury.
出处
《军事医学科学院院刊》
CSCD
北大核心
2007年第5期440-443,447,共5页
Bulletin of the Academy of Military Medical Sciences
基金
贵州省高层次人才特助经费(20040517)
贵州省科技基金(2004-3004)
