Role Of P38 MAPK Activation In High Glucose-induced Microvascular Hyperpermeability In Rats

Objective In type 1 and type 2 diabetes, the main etiological factor of vascular complications would be the toxic effects of hyperglycemia. During the progresses of diabetes, increase in vascular permeability is the first displaying event and reason of upcoming pathological changes, indicating the development of vascular complications. It would be meaningful to clarify the relationship between hyperglycemia and hyper-permeability and to elucidate the underlying mechanisms. In this study, SD rats were used to reproduce type 1 diabetes model. By determination of mesentery microvascular permeability and observation of cytoskeleton distribution in vascular endothelial cells, we revealed the hyper-permeability response in diabetes rats and the role of p38 mitogen-activated protein kinase (p38 MAPK) activation in high glucose-induced microvascular hyperpermeability.Methods Diabetes model were reproduced by intraperitoneal injection of streptozotocin(STZ) to SD rats. The rats were randomly divided into 5 groups,including normal, diabetes, control, MKK6b(A) and MKK6b(E) groups. The permeability coefficient to albumin (Pa) was measure in venules of in vivo mesenterium using a fluorescence ratio technique. Morphological changes of microvascular endothelial cytoskeleton were monitored by observing F-actin...