摘要
目的:探讨FTY720对Ⅰ型糖尿病大鼠的干预作用及机制。方法:选用雄性SD大鼠,用高能量饲料结合低剂量链脲佐菌素(STZ,30 mg/kg,腹腔注射)给予大鼠,建立Ⅰ型糖尿病大鼠模型。造模成功后分为2组:模型组和FTY720组,另选同周龄大鼠作为正常对照组。FTY720组给予1 mg/kg FTY720,正常对照组和模型组给予等量自来水。结果:FTY720组心脏功能显著恢复。FTY720可激活糖尿病心血管内皮细胞S1P1的表达,而降低了S1P3及PKCβⅡ的表达量,恢复糖尿病心血管内皮细胞的迁移能力,恢复高糖诱导的心血管内皮细胞异常升高的通透性。结论:本研究表明,S1P1和S1P3下调导致是糖尿病心血管功能障碍并发症的重要反应通路。FTY720减轻由糖尿病引起的心脏微血管功能损害,和病理性新生血管生成,该功能依赖PKCβⅡ信号通路。因此,FTY720提供了一种潜在的糖尿病心血管功能损害治疗方法。
Objective To study the mechanism of FTY720 on type Ι diabetic rats. Methods The typeⅠ diabetes rat model was established by feeding male SD rats with high energy urea and injecting into the abdominal cavity with low dose cephalosporins（STZ, 30 mg / kg）. In the following, the treated rats were divided into two groups ： model group and FTY720 group. Another group of untreated rats was assigned as normal control group. FTY720 group was given 1 mg / kg FTY720, the normal control group and model group was given the equal amount of water. Results The cardiac function of FTY720 group was recovered markeyly. FTY720 activated the expression of vascular endothelial cells S1P1, diabetes and reduced the expessions of S1P3 and PKCβ Ⅱ and it restored the migration ability of diabetes cardiovascular endothelial cell, as well as the abnormally elevated cardiovascular endothelial cells induced by high sugar permeability. Conclusion The S1P1 and S1P3 cut is an important reaction pathway to the complications of diabetes and cardiovascular dysfunction.FTY720 may reduce the damage to core blood vessels caused by diabetes, and pathological angiogenesis which functionally depends on the PKCβⅡ signaling pathways. Therefore, FTY720 may provide a potential therapy for cardiovascular function impaired by diabetes.
出处
《实用医学杂志》
CAS
北大核心
2016年第20期3293-3295,共3页
The Journal of Practical Medicine
基金
国家自然科学基金项目(编号:81273778
81302994)
