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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 observe the protective effect of Simvastatin, a inhibitor of hydroxyglutaryl coenzyme A (HMG CoA) reductase inhibitor, on renal function in rats with nitric oxide deficiency-type hypertension and to explore its mechanism. Methods: Nitric Oxide Deficiency Hypertension rat model was induced by nitric oxide synthase inhibitor L NAME. 24 WKY rats were randomly divided into normal control group (C), hypertension group (L) Simvastatin group (L + S group). Urine was collected for 24 hours to determine urine β2 microglobulin (β2 M) and urinary protein. The specimens were collected and killed at the 8th week. Nitric oxide (NO), endothelin (ET 1), angiotensin Ⅱ (Ang Ⅱ) level. RESULTS: Blood pressure was increased in 2 weeks after administration of L NAME and significantly increased at week 8 (1 76.5 ± 3.5) mmHg. Compared with group C, urinary protein and β2M formed two peaks at day 7 and 8 in group L, and the proteinuria in group L was (40.5 ± 1.04) mg Lvs 15.28 ± 2 .1 6 mg L and (8.4 ± 5 .62) g Lvs (1 3.6 ± 3.36) mg L (P <0.01) respectively. Urinary β2 M was (0 .5 ± 0.11) mg Lvs (0.29 ± 0.06) mg L and (0.64 ± 0.04) mg Lvs (0.34 ± 0.06) mg L (P <0.01). There were significant differences in NO, ET 1 and AngⅡ levels at 8 weeks (P <0.05). Simvastatin did not affect the blood pressure and blood lipid conditions, reducing urinary protein and urinary excretion of β2 M, the most obvious on the 7th to the 2nd week (P <0. 05); the rat kidney, especially the renal cortex NO levels increased, ET 1 and Ang Ⅱ levels decreased. ?