Change Of Endothelin-1 And Calcitonin Gene-related Peptide Expression In Brain Tissue Of Diabetic Rats With Prestroke Status Caused By Artificial Cold Exposure

Objective We have observed the rats modes of type 2 diabetes mellitus to study the contents changes of ET-1 and CGRP before the stroke under artificial cold exposure (ACE), to evaluate the influence of the endothelin-1(ET-1) and CGRP on Stroke-prone state and to predict the occurrence of stroke.Methods We establish a rats modes of type 2 diabetes mellitus(DM) by feeding high sugar and fat diet and subsequently injecting small dose streptozotocin(STZ). DM model rats and normal control rats were randomly assigned two groups:ACE and non-ACE..The ACE group was designed as 3 cycles of 12h light of 22℃and 12h dark of 4℃.The non-ACE group was kept at 22℃throughout the experiment. Body weight and blood glucose were measured before and after ACE treatment. Set the 3 days cold exposure as the end point, the rat brains were removed quickly and then perfusion (except dead mouse) for immunohistochemistry in the study endpoint. Before stroke occurred, every 5 sections were taken randomly from each rats used for immunohistochemical to detection the protein expression of ET-1 and calcitonin gene-related peptide(CGRP) in rat brain vascular endothelial. The stroke rats were out of the analysis.Result1.Replication of DM model: DM group showed the typical symptoms of diabetes of human such as more drinking, eating, polyuria and weight loss after injection of STZ; and emerged hyperglycemia, hyperinsulinmia and insulin resistance, which showed the statistical significance.2.The protein expression of ET-1 and CGRP(immunohistochemistry) in the brain tissue: In DM model group, the expression of ET-1 and CGRP in the brain tissue were higher (P=0.000) than the control group. After ACE treatment, in DM group, ET-1 were significantly higher than non-ACE group(P=0.003), while CGRP was significantly lower than the non-ACE group (P=0.000); and there were showed no significant changes of ET-1 and CGRP in the control group. Conclusion1. We successfuly establish the rat model of type 2 diabetes mellitus by fed with high sugar and fat diet for 4 weeks,rats were injected a low dose of STZ intrapenitoneally.2.The expression of ET-1 and CGRP could increase in type 2 diabetic rats.Type 2 diabetes could change the vascular endothelial function.3. In DM group, ET-1 were significantly higher while CGRP was significantly lower; and there were showed no significant changes of ET-1 and CGRP in the control group.Cold as a incentives will further aggravate the damage of vascular endothelial function, which result the vasomotor function disorder then forming an environment conducive stroke which is closer to pre-stroke state.