P38 MAPK激活在高血糖致大鼠微血管通透性增高过程中的作用

目的研究P38 MAPK信号传导通路在糖尿病大鼠微血管内皮细胞通透性增高中的作用机制。方法SD雄性大鼠,腹腔注射链脲佐菌素(STZ 55 mg/kg)制备糖尿病模型。分正常组、糖尿病组、溶剂对照组、MKK6b(A)组和MKK6b(E)组。溶剂组:给予相同容量的柠檬酸缓冲液;MKK6b(A)组:在糖尿病模型基础上,实验前24 h尾静脉注射MKK6b(A)2.5 mL/kg;MKK6b(E)组:在实验前24 h给正常大鼠尾静脉注射MKK6b(E)2.5 mL/kg。用荧光强度检测微血管通透性;用荧光染色法观察微血管内皮细胞骨架蛋白的形态。结果糖尿病大鼠的微血管通透性明显高于正常组;注射MKK6b(E)可以增高大鼠微血管的通透性,而注射MKK6b(A)后微静脉的高通透性则被抑制。结论P38 MAPK信号转导系统参与介导了糖尿病微血管通透性增高的反应过程。

Role of P38 MAPK activation in glucose-induced microvascular hyperpermeability of rats

Objective To study the role of P38 mitogen-activated protein kinase(P38 MAPK) activation in high level glucose-induced microvascular hyperpermeability.Methods Rats were induced to diabetis by intraperitoneal injection of streptozotocin(STZ).The rats were divided into 5 groups,including normal,diabetes,control,MKK6b(A) and MKK6b(E) groups.The permeability coefficient to albumin(Pa) was measured in venules of in vivo mesenterium using a fluorescence ratio technique;Morphological changes of microvascular endothelial cell were monitored by observing fluorescence of F-actin stained with rhodamine-phalloidin.Results The permeability of diabetic rats was obviously increased.The activation of P38 MAPK by MKK6b(E) could increase microvascular permeability in normal rats,and the inhibition of P38 MAPK by MKK6b(A) could inhibit hyperpermeability of diabetic rats.Conclusion The activation of P38 MAPK induced by hyperglycemia may play a role in diabetic microvascular hyperpermeability.