摘要
目的观察糖尿病大鼠肾小管P-选择素、单核细胞趋化蛋白-1(MCP-1)、蛋白激酶Cα(PKCα)、p38MAPK表达的动态变化,探讨相互间关系及在糖尿病肾病(DN)发生发展中的作用。方法把链脲佐菌素诱导的糖尿病大鼠随机分为5组,每组设正常对照组。免疫组化法检测肾小管P-选择素、MCP-1、PKCα和p38MAPK、纤维连接蛋白(FN)的表达;Western blot检测p38MAPK蛋白;PAS染色,光镜观察肾组织形态;生化方法测血糖、血肌酐及尿蛋白。结果随着糖尿病病程发展,肾小管P-选择素、MCP-1、PKCα、p38MAPK和FN表达逐渐增加。糖尿病4周,P-选择素和MCP-1表达十分显著,两者呈正相关,并且与PKCα、p38MAPK和FN也呈正相关。结论DM病理信号可能通过PKCα和p38MAPK介导,而诱导肾小管P-选择素和MCP-1表达,参与DN的发病机制。
[Objective] To observe the dynamic changes of expression of P-selectin, monocyte chemoattractant protein-1 (MCP-1), PKCα and p38MAPK in the renal tubules of diabetic rats and to investigate their relationship with eath other on a time course. [Methods] STZ-induced diabetic rats were randomly divided into five groups, every group has a normal age-matehed control group. Immunohistochemistry was employed to detect the expression of P-Selectin, MCP-1, PKCα, p38MAPK and FN in the kidney, p38MAPK protein in the renal cortex was checked by Western blot. The morphological changes of renal tissue were checked through light microscopy in PAS staining sections. Blood glucose, creatinine and 24 hours urine protein were analysed by chemical methods. [Results] With development of diabetes, the expression of MCP-1, P-Selectin, PKCα, p38MAPK and FN in renal tubules of diabetic groups were increased comparing with those of normal age-matehed control group (P 〈0.05). In DM week 4, the expression of P-Selectin and MCP-1 were quite remarkable, and they positively correlated with the expression of PKCα, p38MAPK and FN (P 〈0.05). [Conclusion] An increase in p38MAPK and PKCα induced by diabetic condition up-regulated the expression of MCP-1 and P-Selectin in the renal tubules which might participate in the pathogeneses of the diabetic nephropathy in diabetic rats.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2007年第9期1051-1054,1058,共5页
China Journal of Modern Medicine
基金
贵州省高层次人才特助经费(20040517)
贵州省科技基金(2004-3004)
贵州省省长资金(2005-303)