罗格列酮对改善糖尿病大鼠心肌微血管内皮细胞功能的影响  

Rosiglitazone Amends Myocardial Microvascular Endothelial Function in Diabetic Rats

作　　者：程训民[1] 江时森[1] 马瑞[1] 宫剑滨[1] 周航波[1] 毛广平[1] 

机构地区：[1]南京军区南京总医院,江苏南京210002

出　　处：《中国微循环》2008年第2期85-88,共4页Journal of Chinese Microcirculation

基　　金：江苏省六大人才高峰资助项目(编号:2005A6)

摘　　要：目的探讨罗格列酮对糖尿病大鼠心肌微血管内皮细胞功能的影响。方法腹腔注射小剂量链脲佐菌素结合高能量饲料制备2型糖尿病大鼠模型,随机分为未治疗组与治疗组:罗格列酮4mg/(kg.d)。16周后定量测定血管内皮损伤标志物:可溶性血管内皮细胞蛋白C受体(sEPCR)、可溶性血栓调节蛋白(sTM)、血管性血友病因子(vWF)和一氧化氮(NO)的血浆浓度。分光光度法及免疫组化法分别测定心肌组织内NO浓度、NO合酶(NOS)的活性及内皮型NO合酶(eNOS)在微血管内皮细胞的表达。结果罗格列酮治疗组血糖及血浆中sEPCR、sTM、vWF显著低于未治疗组,但高于非糖尿病对照组。与未治疗组比较,罗格列酮治疗组心肌组织中NO、结构型NOS(cNOS)含量增高,eNOS阳性反应产物量增多,而诱导型NOS(iNOS)含量降低。结论罗格列酮可以降低糖尿病大鼠血糖,减轻内皮细胞损伤与改善心肌微血管内皮细胞功能,有助于减少糖尿病时心肌微血管病的发生与发展。Objective To investigate the effect of rosiglitazone treatment on cardiac microvascular endothelial cell function in diabetes mellitus rats. Methods Type 2 diabetic rats were induced by an intraperitoneal injection of low doses of streptozotocin combined with high fat diet, and were randomized to rosiglitazone treatment（4mg/kg/d） or vehicle treatment for 16 weeks. Plasma soluble endothelial protein C receptor （sEPCR）, soluble thrombomodulin（sTM）, von Willebrand factor（vWF）, and nitric oxide（NO） were determined. The NO concentration and all isoforms of nitric oxide synthase（NOS） activity of cardiac tissue homoge- nate and expression of endothelial nitric oxide synthase（eNOS） were detected by spectrophotometer and immunohistochemistry, respectively. Results The levels of sEPCR, sTM, and vWF and the level of plasma glucose were significantly lower in diabetic rats treated with rosiglitazone compared with untreated group but higher than non-diabetic control. Compared with untreated group, the NO concentration and constitutive NOS（cNOS） activity and the expression of eNOS in myocardium in diabetic rats treated with rosiglitazone were significantly increased, but the inducible NOS（iNOS） activity in diabetic rats treated with rosiglitazone was significantly reduced. Condusion Rosiglitazone significantly reduces blood glucose and amends cardiac capillary endothelial function in type 2 diabetic rats. It is suggested that rosiglitazone administration may attenuate the development of cardiac microvascular disease in diabetes.

关 键 词：糖尿病 心肌毛细血管 内皮细胞 PPARΓ激动剂 

分 类 号：R587.1[医药卫生—内分泌]