• 实验研究 •    

口服螺内酯对SHR心肌组织TNF-α表达的影响

赵红   

  1. 河北联合大学附属医院
  • 收稿日期:2011-04-26 修回日期:2011-07-29 出版日期:2012-01-15 发布日期:2012-01-15
  • 通讯作者: 赵红

The change of TNF-αexpression in myocardiac tissue of the spontaneous hypertension rats by oral spironolactone

  • Received:2011-04-26 Revised:2011-07-29 Published:2012-01-15 Online:2012-01-15

摘要: [摘要] 目的 观察口服小剂量螺内酯对SHR大鼠心肌组织TNF-α表达水平的影响 方法 20只8周龄雄性SHR随机分为SHR-SPIRO( 螺内酯组,n=10) 和SHR-CON(安慰剂组,n=10),另设WKY组 (Wistar-kyoto,n=7)。SHR-SPIRO组螺内酯双蒸水溶解,20mg/kg.d灌胃,SHR-CON和WKY组等容积双蒸水灌胃,持续16周,24周龄大鼠称取体重,颈动脉插管检测动脉血压。摘取心脏,心尖部横断为两片,分别投入液氮罐中和10%中性甲醛固定液中,用ELASA方法检测心肌组织匀浆上清液TNF-α水平,免疫组化观察TNF-α表达。结果 1. 螺内酯组与安慰剂组比较,收缩压、舒张压、平均动脉压水平无明显变化(SHR-SPIRO: 174.64±19.6;121.65±19.45;148.4±18. 5 vs SHR-CON: 184.19±8.55;136.76±22.06;150.5±24.5 p>0.05),但两组的收缩压、舒张压、平均动脉压均明显高于WKY组,差别有统计学意义。2. 安慰剂组与WKY组比较,心肌组织TNF-α水平明显升高,(ELASA法24.52±3.36 vs 1.53±0.21 p<0.05),差别有统计学意义;螺内酯组与安慰剂组比较心肌组织TNF-α水平降低(ELASA法5.9±0.96vs 24.52±3.36 p<0.05),差别有统计学意义 但未达WKY组水平。结论 SHR大鼠心肌组织TNF-α高表达,口服小剂量螺内酯可降低SHR大鼠心肌组织TNF-α水平。

关键词: 自发性高血压大鼠, 醛固酮, 螺内酯, TNF-α, 心肌纤维化

Abstract: Abstract :Objective  To investigate the effects of oral spironolactone on expression of TNF-αin the myocardiac tissue of spontaneous hypertension rats during t he progressing stage of hytertension. Methods  Twenty eight 2-weeks- old male spontaneous hypertension rats (SHR) were divided randomly into spironolactone group (SHR-SPIRO , n = 10),and control group (SHR-CON , n = 10) ,sex - age matched Wistar Kyoto rats (WKY group , n = 7) which having normal hypertension were also used as the third group . The spironolactone was solved with distilled water and the animals were weighed once weekly to adjust for drug dosage(20mg/kg.d).Evaluation were performed after 16 weeks of treatment.The rats were anesthetized at 24-week-old with 1g/kg urethane intraperitoneal. The systolic pressure,diastolic pressure, mean arterial blood pressure were deteced by a tube that was pierced into the carotid artery that was connected with physiological function experimental system. The hearts were rapidly isolated and were cut into two parts. The one was fixed in 10% buffered for immunohistochemistry;The other one was throwed quickly into liquid nitrogen . The TNF-αlevels of left ventricular homogenate were deteced by enzyme linked immunosorbent assay. Results The systelic blood pressure,diastolic blood pressure and mean arterial pressure had no differences in the rats between SHR-SPIRO group and SHR-CON group. (SHR-SPIRO: 174.64±19.6;121.65±19.45;148.4±18. 5 vs SHR-CON: 184.19±8.55;136.76±22.06;150.5±24.5 p>0.05).but the artery blood pressure of the two groups are higher than the WKY group. The concentration of TNF-α is higer in myocardiac tissue in the SHR-CON group than WKY group(24.52±3.36 vs 1.53±0.21 p<0.05 ); TNF-α expression decrease significently in SHR-SPIRO group than SHR-CON group(5.9±0.96vs 24.52±3.36 p<0.05 ).Conclusion 1. The levels of myocardial tissue of SHR is higer than the normal hypertension WKY rats;2.Oral spironolactone can decrease concentration of TNF-α of myocardial tissue in hypertension rats.

Key words: spontaneous hypertension rats, aldosterone, spironolactone, TNF-α, myocardial fibrosis