罗格列酮对1型糖尿病大鼠血管结构及磷脂酶A2表达的影响

目的探讨过氧化物酶增殖物激活受体-γ（PPARγ-）配体罗格列酮对糖尿病大鼠血管病变的影响及可能机制。方法 24只SD大鼠随机分为正常对照组、糖尿病组和糖尿病罗格列酮治疗组。糖尿病组和糖尿病罗格列酮治疗组大鼠以链脲佐菌素（STZ）腹腔注射（60 mg/kg）诱导建立1型糖尿病大鼠模型,后者于血糖稳定第2周开始每日给予罗格列酮灌胃（1 mg/kg）,连续8周。第8周末,各组大鼠在2.5%戊巴比妥腹腔注射麻醉下,心脏取血经ELISA法检测血清经典炎症通路上游炎症因子磷脂酶A2（PLA2）水平;取胸腹主动脉,观察血管壁组织形态学及超微结构改变,免疫组织化学法检测血管壁PLA2蛋白表达。结果与正常对照组比较,糖尿病组大鼠血管结构破坏严重;局部PLA2蛋白表达增加,血清PLA2水平上升。糖尿病罗格列酮治疗组大鼠血管病变明显轻于糖尿病组;血管壁组织PLA2蛋白表达和血清PLA2水平明显高于对照组,但显著低于糖尿病组（P〈0.05）。结论罗格列酮对糖尿病大鼠血管结构具有保护作用,其机制可能与抑制外周和局部炎症因子PLA2表达而减轻炎症反应有关。

Effects of Rosiglitazone on vascular structure and expression of phospholipase A2 in rats with type 1 diabetes mellitus

Objective To investigate the effects of rosiglitazone on vascular lesions in rats with diabetes mellitus, and explore its possible mechanism. Methods Twenty-four SD rats were randomly divided into normal control group, diabetes mellitus group and diabetes mellitus rosiglitazone treatment group. Rat models of type 1 diabetes mellitus were established in diabetes mellitus group and diabetes mellitus rosiglitazone treatment group by intraperitoneal injection of 60 mg/kg of streptozocin (STZ), and intragastric administration of rosiglitazone (1mg/kg) was conducted in diabetes mellitus rosiglitazone treatment group for 8 weeks from the second week after glucostasis. At the end of the eighth week, heart blood samples were collected from each group of rats, and ELISA was employed to detect the levels of phospholipase A2 (PLA2). Besides, thoracoabdominal aorta were obtained, histomorphology and ultrastructure changes of vessel wall were observed, and expression of PLA2 protein of vessel wall was detected by immunohistochemistry. Results Compared with normal control group, the vascular structure of rats in diabetes mellitus group was damaged severely, both local PLA2 protein expression and serum PLA2 level increased. The vascular lesions in diabetes mellitus rosiglitazone treatment group were less severe than those in diabetes mellitus group. The expression of PLA2 protein of vessel wall and serum PLA2 level in diabetes mellitus rosiglitazone treatment group were significantly higher than those in control group, and significantly lower than those in diabetes mellitus group (P<0.05). Conclusion Rosiglitazone has protective effects on vascular structure of rats with diabetes mellitus, and the mechanism may relate to the inhibition of PLA2 expression and reduction of inflammation.