Mahfouz M M, Kummerow F A
University of Illinois, The H. E. Moore Heart Research Foundation Champaign, IL 61820, USA.
Prostaglandins Other Lipid Mediat. 2005 May;76(1-4):59-73. doi: 10.1016/j.prostaglandins.2004.12.002. Epub 2005 Feb 25.
The effect of atorvastatin (Lipitor) on diabetes-induced changes in plasma lipids, oxidative stress and the ability of aortic tissues to generate prostacyclin was studied in streptozotocin diabetic rats. In diabetic rats, plasma total cholesterol, triglycerides and serum glucose significantly increased compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not affect hyperglycemia but significantly reduced plasma total cholesterol and triglycerides compared to diabetic rats. The oxidative stress markers urinary isoprostane, liver thiobarbituric acid reactive substances (TBARS) and plasma protein carbonyl content significantly increased in diabetic rats compared to nondiabetic rats. Atorvastatin admnistration to diabetic rats significantly reduced oxidative stress levels compared to diabetic rats, but urinary isoprostane and liver TBARS remained significantly higher than nondiabetic rats. Prostacyclin (PGI(2)) generation by aortic tissues significantly decreased in diabetic rats compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not reverse that inhibition. These results were discussed in the light of the possible effects of hyperglycemia and statins on NAD(P)H-oxidase and cyclooxygenase-2 activities and the genetic difference between rats and other mammals regarding the level of vascular superoxide dismutase (SOD) activity.
在链脲佐菌素诱导的糖尿病大鼠中,研究了阿托伐他汀(立普妥)对糖尿病引起的血浆脂质变化、氧化应激以及主动脉组织生成前列环素能力的影响。与非糖尿病大鼠相比,糖尿病大鼠的血浆总胆固醇、甘油三酯和血清葡萄糖显著升高。给糖尿病大鼠施用阿托伐他汀对高血糖没有影响,但与糖尿病大鼠相比,显著降低了血浆总胆固醇和甘油三酯。与非糖尿病大鼠相比,糖尿病大鼠的氧化应激标志物尿异前列腺素、肝脏硫代巴比妥酸反应性物质(TBARS)和血浆蛋白羰基含量显著增加。与糖尿病大鼠相比,给糖尿病大鼠施用阿托伐他汀显著降低了氧化应激水平,但尿异前列腺素和肝脏TBARS仍显著高于非糖尿病大鼠。与非糖尿病大鼠相比,糖尿病大鼠主动脉组织生成的前列环素(PGI(2))显著减少。给糖尿病大鼠施用阿托伐他汀并未逆转这种抑制作用。根据高血糖和他汀类药物对NAD(P)H氧化酶和环氧化酶-2活性的可能影响以及大鼠与其他哺乳动物在血管超氧化物歧化酶(SOD)活性水平上的遗传差异,对这些结果进行了讨论。