辛伐他汀对一氧化氮缺乏性高血压大鼠早期肾功能的影响

The Effects of Simvastatin on Renal Function of the Rats with Deficient Nitric Oxide

目的 :观察羟甲基戊二酰辅酶A(HMG CoA)还原酶抑制剂辛伐他汀 (Simvastatin)对一氧化氮缺乏性高血压大鼠肾功能的保护作用 ,并探讨其机制。方法 :通过给予一氧化氮合酶抑制剂L NAME制造一氧化氮缺乏性高血压大鼠模型 ,2 4只WKY大鼠随机分为正常对照组 (C组 )、高血压组 (L组 )、辛伐他汀组 (L +S组 )。收集 2 4h尿液测定尿 β2 微球蛋白 (β2 M)、尿蛋白 ,第 8周宰杀收集标本 ,检测血和肾组织中一氧化氮 (NO)、内皮素 (ET 1 )、血管紧张素Ⅱ (AngⅡ )水平。结果 :给予L NAME2周即见血压升高 ,第 8周时显著升高 ,达 (1 76 .5± 3.5 )mmHg。与C组比较 ,L组第 7天和第 8周时尿蛋白及 β2 M形成两个高峰 ,尿蛋白分别为 (4 0 .5± 1 0 .4 6 )mg Lvs 1 5 .2 8± 2 .1 6mg L和 (8.4± 5 .6 2 )g Lvs(1 3.6 5± 3.36 )mg L(P <0 .0 0 1 ) ,尿 β2 M分别为 (0 .5 8± 0 .1 1 )mg Lvs(0 .2 9± 0 .0 6 )mg L和 (0 .6 4± 0 .0 4 )mg Lvs(0 .34± 0 .0 6 )mg L(P <0 .0 1 )。 8周时肾脏局部NO、ET 1及AngⅡ水平均有显著差异 (P <0 .0 5 )。辛伐他汀在不影响血压和血脂条件下 ,减少尿蛋白和尿β2 M排出 ,以第 7天至 2周时最明显 (P <0 .0 5 ) ;使大鼠肾脏局部 ,特别是肾皮质NO水平增高 ,ET 1及AngⅡ水平降低。?

Objective:To investigate the effects of Simvastatin, which is a kind of 3 hydroxy 3 methylglutaryl coenzyme(HMG CoA)reductase inhibitor,on the renal function in nitric oxide deficient hypertensive rat and its mechanism.Methods:The model of NO deficient hypertensive rat was established by giving nitric oxide synthase(NOS)inhibitor L NAME.Twenty four WKY rats were randomized to three groups with 8 animals each:Control (group C),group L:L NAME 50mg/kg·d -1, and group L+S:L NAME 50 mg/kg·d -1 + Simvastatin 5 mg/kg·d -1 .Urinary of 24 hours was collected to measure urinary protein(UP)andβ 2 microglobulin protein(Uβ 2 M)at indicated time point.Rats were sacrificed after 8 weeks and the levels of NOx -,endothelins(ET 1),angiotensinⅡ(AngⅡ)were measured in plasma and renal tissue.Results:Blood pressure of the rats began increasing after given L NAME for two weeks and reached the highest level at week 8.In group L UP and Uβ 2 M showed two peaks at week 1 and week 8,respectively and much higher than those in group C.UP was 40.5±10.46 mg/L vs 15.28±2.16 mg/L at week 1 and 48.4±5.62 mg/L vs 13.65±3.36 mg/L at week 8( P < 0.001 ),while Uβ 2 M was 0.58 ±0.11 mg/L vs 0.29±0.06 mg/L at week 1 and 0.64±0.04 mg/L vs 0.34±0.06 mg/L at week 8.The levels of NO、ET 1 and AngⅡ were significant difference in renal tissue after 8 weeks ( P <0.05).Simvastatin did not affect blood pressure and lipid,but declined the levels of UP and Uβ 2 M,especially during week 1 to week 2.Simvastatin had no significant effect on the levels of plasma NO、ET 1 and AngⅡ,but increased the level of NO and decreased the levels of ET 1 and AngⅡmarkedly in renal tissue,especially in kidney cortical of rat.Conclusion:Simvastatin has protective effects on renal function in NO deficient hypertensive rat via regulating the endothelial function and the level of AngⅡin renal tissue.