瑞舒伐他汀改善糖尿病大鼠血管内皮功能的实验研究

Therapeatic effects of two different dosage of rosuvastatin on endothelial dysfunction in diabetic rats

目的评价不同剂量瑞舒伐他汀对糖尿病大鼠血管内皮功能的保护作用。方法24只糖尿病大鼠随机分为3组：糖尿病对照组、瑞舒伐他汀20mg组（RV20mg组）和10mg组（RV10mg组）；8只健康SD大鼠作为正常对照组。给药共8周，分别于给药前和给药后第8周测定血浆内皮素-1（ET-1）、一氧化氮（NO）、血糖、血脂含量。结果用药前糖尿病大鼠各组血糖均显著高于正常对照组（P〈0．01）；RV20mg和RV10mg组在给药后第8周血糖稍低于糖尿病对照组，但差异无统计学意义（P〉0．05）。糖尿病对照组血浆NO浓度明显低于SD正常对照组（P〈0．05），给药8周后，用药组血浆NO浓度明显高于糖尿病对照组（P〈0．01或P〈0．05）。糖尿病对照组血浆ET-1浓度高于SD正常对照组（P〈0．05）；给药8周后，用药组血浆ET-1浓度明显低于糖尿病对照组（P〈0．01或P〈0．05）。RV20mg组和RV10mg组比较，血浆ET-1浓度降低及血浆N0浓度升高（P〈0．05）。同时，RV20mg组和RV10mg组血胆固醇水平明显低于糖尿病对照组（P〈0．01）。结论瑞舒伐他汀可明显降低糖尿病大鼠的血胆固醇水平，同时通过提高血浆NO浓度和降低ET-1浓度等机制改善血管内皮功能。

Objective To evaluate the effects of two different dosage of rosuvastatin on endothelial dysfunction in diabetic rats. Methods The 24 diabetic rats were randomly divided into three groups （n= 8, each） ： diabetic control group, 20 mg rosuvastatin daily （RV 20 mg group） and 10 mg rosuvastatin daily for 8 weeks （RV 10 mg group） and normal control group （SD group）. The levels of blood glucose, lipid, nitric oxide（NO） and endothelin-1 （ET-1） were measured before and 8 weeks after treatment. Results The levels of blood glucose were higher in all diabetic rats groups than in SD group before experiment （P〈0.01）. Compared with diabetic rats control group, blood glucose was slightly lower in RV 10 mg group and RV 20 mg group at 8 weeks （P〈0.05）. The plasma NO level was significantly lower in diabetic rats control group than in SD group （P〈0.05）. After 8 weeks, plasma NO levels were significantly higher in RV 20 mg and RV 10 mg groups than in diabetic rats control group （P〈0.01 or P〈0.05）. The plasma levels of ET-1 was significantly higher in diabetic rats control group than in SD group （P〈0.01）. After 8 weeks, plasma ET-1 levels were significantly lower in RV 20 mg and RV 10 mg group than in diabetic rats control group （P〈0.01）. Meanwhile, the plasma lipids were lower in RV 20 mg and RV 10 mg group than in diabetic control group （P〈0.05 or P〈0.01）. Conclusions Rosuvastatin can adjust blood lipids and significantly improve endothelial function in diabetic rats by increasing plasma NO level and decreasing plasma ET-1 level.