E3泛素连接酶Siah-1与糖尿病血管内皮损伤的关系研究

Relationship between E3 ubiquitin ligase SIAH1 and diabetic vascular endothelial injury

摘要:

目的  探讨E3泛素连接酶Siah-1与糖尿病血管内皮损伤的关系。方法  器官浴槽和血管张力系统测定雄性C57BL/6小鼠，以及雄性db/db糖尿病小鼠的离体胸主动脉血管张力；蛋白质印迹法（Western blot）和酶联免疫吸附法（ELISA）测定小鼠Siah-1和连环蛋白（β-catenin）水平。结果  糖尿病小鼠离体胸主动脉血管对乙酰胆碱（Ach）引发的舒张反应低于正常小鼠（t =24.270，P =0.000），Siah-1抑制剂孵育30 min的糖尿病小鼠对Ach引发的舒张反应与正常小鼠无明显差异（t =1.991，P =0.327）。各组小鼠对硝普钠（SNP）引发的血管舒张呈现良好的反应，差异无统计学意义（F =0.145，P =0.541）。经Siah-1抑制剂处理的糖尿病小鼠Siah-1浓度明显降低（t =5.483，P =0.017），而β-catenin浓度明显升高（t =6.670，P =0.023）。在有β-catenin抑制剂的情况下，使用Siah-1抑制剂的糖尿病小鼠血管内皮舒张反应明显低于正常小鼠（t =1.441，P =0.378）。结论  E3泛素连接酶Siah-1参与了糖尿病血管内皮损伤的过程，其机制可能与对β-catenin信号通路的影响有关。

Abstract:

 Objective To investigate the relationship between E3 ubiquitin ligase SIAH1 and diabetic vascular endothelial injury. Methods C57BL/6 rats and db/db rats were used in our study. Tension of isolated thoracic aorta was measured by organ bath and the vascular tension system. The levels of SIAH1 and β-catenin were detected by Western blot and ELISA. Results The vascular endothelial diastolic reaction induced by acetylcholine (Ach) in the db/db rats was significantly lower than that of the normal rats (t = 24.270, P = 0.000). There was no significant difference in the vascular endothelial diastolic reaction induced by Ach between the db/db rats using SIANH1 inhibitor and the normal rats (t = 1.991, P = 0.327). There was no significant difference in the vascular endothelial diastolic reaction induced by sodium nitroprusside (SNP) between the db/db rats and the normal rats (F = 0.145, P = 0.541). The level of SIAH1 decreased (t = 5.483, P = 0.017) and that of β-catenin increased (t = 6.670, P = 0.023) in the db/db rats using SIAH1 inhibitor. In the presence of β-catenin inhibitor, the vascular endothelial diastolic reaction of the diabetic rats using SIAH1 inhibitor had no significant difference from that of the normal rats (t = 1.441, P = 0.378). Conclusions E3 ubiquitin ligase SIAH1 is involved in the process of vascular endothelial injury in diabetes, the mechanism may be related to its effect on β-catenin signal pathway.