氯沙坦对自发性高血压大鼠氧化应激及肾功能的影响

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目的观察氯沙坦对自发性高血压大鼠氧化应激及肾功能变化的影响,探讨氯沙坦对高血压肾损害早期的保护机制。方法选取雄性10周龄的Wistar Kyoto(WKY)大鼠6只和同周龄的自发性高血压大鼠(SHR)12只,SHR又随机分为高血压组及高血压药物干预组(Losartan组)。氯沙坦组按每只大鼠30mg/kg/day的计量灌胃,根据大鼠体重,每周调整药物剂量一次。WKY组及正常SHR组每日灌胃同体积的生理盐水。每周测量大鼠血压、体重。8周后,肾组织HE染色,观察其形态学变化;放射免疫分析法(radioimmunoassay,RIA)测定尿β2-微球蛋白的含量;比色法测定血肌酐、尿素氮、NO、SOD、MDA水平。结果高血压组SCr、BUN水平较同期WKY组有所增加但无统计学意义,但β2-微球蛋白明显增加,氯沙坦治疗后显著降低;高血压组NO、SOD、MDA水平较同期WKY组均显著性升高,氯沙坦治疗组各指标明显降低。结论氧化应激可能参与了高血压肾损害的发病机制;氯沙坦对自发性高血压肾损害有一定的保护作用;氯沙坦对自发性高血压肾病的防治可能部分通过改善氧化应激作用实现。“,” objective The present study was designed to observe the effect of Losartan on the the Oxidative Stress and Renal Function in the Spontaneously hypertensive rats, to explore the protection mechanisms of the early indices of renal damage in the Spontaneously hypertensive rats. Methods Six 10-weeks-old male Wistar Kyoto rats were set as normal control(WKY group) , twelve age ?matched male Spontaneously hypertensive rats were divided randomly into untreated group(SHR group) and treated group(6 rats in each group),treated group fed with Losartan(Los group).Losartan group received 30mg/kg ,once a day. The drugs were distiled water. Systolic blood pressure (SBP) and weight were measured weekly throughout the 8-week period. After 8 weeks, One kidney of each rat was as a source for evaluating the renal pathological changes using Hematoxylin and eosin(HE) staining . The level of β2- microglobulin(β2-MG) in urine was measured by radioimmunoassay. The content of Serum creatinine(SCr), Blood urea nitrogen(BUN), Nitric oxide(NO), Superoxide dismutase(SOD) and Maleic dialdehyde (MDA)were detected with chromatometry. Results Compare with WKY group, No significant difference was found in the study such as Serum creatinine and Blood urea nitrogen, but the level of β2- microglobulin(β2-MG) in urine increased obviously while the Losartan group decreased significantly; The activites of NO ,SOD and MDA were significantly higher than WKY group while the Losartan group decreased significantly. Conclusion Oxidative Stress probably participate in the pathogenesis of hypertensive nephrosclerosis; Losartan possible have a certain protective effect on hypertensive nephrosclerosis Renal protective mechism of Losartan may be, at least partly, correlated with improving the Oxidative stress.
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