The cross-link breaker, N-phenacylthiazolium bromide prevents vascular advanced glycation end-product accumulation
The cross-link breaker, N-phenacylthiazolium bromide prevents vascular advanced glycation end-product accumulation
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DOI：
10.1007/s001250051355
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发表时间：
2000-05-01
期刊：
影响因子：
8.2
通讯作者：
Soulis, T
中科院分区：
文献类型：
--
作者：
Cooper, ME;Thallas, V;Soulis, T
目标/假设。据推测，晚期糖基化在介导糖尿病血管并发症中具有关键作用。噻唑化合物的出现，例如 N-苯甲酰基噻唑溴化物，可以裂解预先形成的晚期糖基化终末产物 (AGE)，使我们能够探索这些药物对与糖尿病相关的血管 AGE 积累和肥大的影响。方法。随机选择对照和链脲佐菌素糖尿病大鼠进行不治疗或治疗。 N-苯甲酰基噻唑溴化物（10 mg/kg 腹腔注射）并随访 3 周。在另一项研究中，将溴化 N-苯甲酰噻唑鎓干预延迟至糖尿病 3 周后，然后给予 3 周（总共 6 周）。结果。通过放射免疫测定和免疫组织化学评估，糖尿病与肠系膜血管晚期糖基化终产物增加有关。 N-溴化苯甲酰噻唑鎓治疗可以防止血管 AGE 积累的增加。仅当从糖尿病诱导时开始使用N-苯甲酰基溴化噻唑治疗时，糖尿病相关的肠系膜血管肥大才会减弱。结论/解释。交联破坏剂似乎可以有效预防或逆转血管中晚期糖基化终产物的积累，并有可能在糖尿病血管并发症的治疗中发挥作用。
Aims/hypothesis. Advanced glycation is postulated to have a pivotal role in mediating diabetic vascular complications. The emergence of thiazolium compounds such as N-phenacylthiazolium bromide which cleave preformed advanced glycation end products (AGEs) has allowed us to explore the effects of these agents on the vascular AGE accumulation and hypertrophy associated with diabetes.Methods. Control and streptozotocin diabetic rats were selected at random for no treatment or treatment with. N-phenacylthiazolium bromide (10 mg/kg intraperitoneally) and followed for 3 weeks. In a separate study, intervention with N-phenacylthiazolium bromide was delayed until after 3 weeks of diabetes and then given for 3 weeks (total of 6 weeks).Results. Diabetes was associated with increased mesenteric vascular advanced glycation end products, as assessed by radioimmunoassay and immunohistochemistry. This increase in vascular AGE accumulation was prevented by N-phenacylthiazolium bromide treatment. Diabetes-associated mesenteric vascular hypertrophy was attenuated by treatment with N-phenacylthiazolium bromide only if given from the time of induction of diabetes.Conclusion/interpretation. Cross-link breakers seem to be effective in preventing or reversing accumulation of advanced glycation end-products in blood vessels and have the potential to play a part in the treatment of diabetic vascular complications.