Effects Of Anion Exchanger-2 On Endothelial Disfunction In Type 2 Diabetic Rats And Its Possible Mechanisms

Objective: To study the effect of AE2 protein on arotic endothelium function in type 2 diabetic rats and its mechanism.Methods: Male SD rats were injected with low dose streptozotocin and fed with diets enriched in fat and sugar to form type 2 diabetic mode1.Then, the rats were dealed with in 4 groups, normal group(NC),diabetes group(DM),diabetes with drug aminoguanidine group(AG), diabetes with drug myxothiazole group (MTZ). After 8 weeks, the expression of AE2 protein and eNOSmRNA in the aorta, the Ach—dependent vasodilation response of isolated aorta,the synthesis of nitric oxide(NO) in serum were detected.We also used the method of RT-PCR and Western-Blotting to improve the mechanism that hight glucose upregulated the expression of AE2mRNA and protein in HUVEC.Results: (1)In DM group fast plasma glucose (18.18±4.04mmol/L), insulin (12.05±3.55 mIU/L),triglyceride(1.26±0.53mmol/L) levers were significantly higher than fast plasma glucose (5.36±0.64mmol/L), insulin (4.82±1.57 mIU/L), triglyceride (0.30±0.08mmol/L) in NC group (P<0.05). This suggested a perfect model made. (2) AE2 protein immnohistochemical expression in aorta endomembrane were significantly upregulated in DM group(0.672±0.018) compared with that in NC group (0.157±0.020), but in AG group(0.321±0.013), MTZ group(0.284±0.024) they were downregulated compared with that in DM group(P<0.05 ). (3) the maximum acetylcholine (Ach) -dependent vasodilation response (EDVRmax) of aorta decreased significantly in DM group compared with that in NC group(P<0.05); In AG,MTZ group EDVRmax recovered partly compared with that in DM group (P<0.05); Interesting, the EDVRmax was negatively correlated with AE2 protein(P<0.01). (4) In DM group, the eNOS mRNA expression were significantly higher and NO concentration were lower than that in NC group (P<0.01),and in AG,MTZ group the eNOS mRNA expression become more higher and NO concentration were higher also (P<0.01).(5) The expression of AE2 mRNA and AE2 protein in the HG group were higher than that in control group (P<0.05); But they decreased after dealed with in MTZ or AG group(P<0.05).Conclusion: AE2 protein induced endothelial disfunction in type 2 diabetes . Depressing the expression of AE2 protein and its function could get a improved EDVR .The mechanism of AE2 induced endothelial disfunction is probably eNOS/NO dependent. Hight glocuse upregulated the expression of AE2 protein though AGEs/ROS pathway.