摘要
目的本研究以内源性锂作为肾脏近端小管钠重吸收的标志物,研究哇巴因-高血压鼠在高血压发展期间,肾脏钠转运的变化情况,以进一步阐明哇巴因在高血压发病机制中的作用。方法将80只80-100g雄性SD大鼠随机分为正常对照组(n=40)和哇巴因组(n=40)。每日分别给予两组大鼠腹腔注射生理盐水1ml/kg或哇巴因27.8μg/kg,每周测量收缩压及体质量各1次。分别于饲养2、4、6和8周后分4批处死动物。处死前1周置于代谢笼中,测定各组每只大鼠摄食量。收集血清及24h尿,测定血清和尿中的钠、锂和肌酐浓度,计算内生肌酐清除率、钠排泄分数、锂排泄分数及远端肾小管钠重吸收率(FDRNa)。结果两组的体质量及食物摄入量在实验的各个阶段均无显著差异(P>0.05)。2周时,哇巴因组血压与对照组相比无显著性差异(P>0.05),4周后哇巴因组血压显著高于对照组(P<0.001)并以一种剂量依赖的方式升高,7周后,血压不再继续升高,处于维持阶段。对照组在整个实验过程中血压与治疗前的基础值相比无显著性差异(P>0.05)。两组的内生肌酐清除率及血清钠在实验的各个阶段均无显著差异(P>0.05)。2、4、6周时哇巴因组的锂排泄分数均显著低于对照组(P<0.01),2周和6周时,哇巴因组的FENa低于对照组,但无统计学差异(P>0.05)。4周时,哇巴因组的钠排泄分数显著低于对照组(P<0.05),表明哇巴因组近端小管钠重吸收的增加,同时伴随着钠排泄的减少。2、4、6周时哇巴因组的钠排泄分数均显著低于对照组(P<0.05),表明远端小管起了一定的代偿作用。8周时,两组的锂排泄分数,钠排泄分数及FDRNa均无显著性差异(P>0.05)。结论哇巴因可以使哇巴因-高血压鼠肾脏近端小管钠重吸收增加,肾排钠减少,导致其压力利钠关系改变,在高血压的发生发展中起着重要的作用。
Objective To investigate the changes in renal sodium transport during development of hypertension in ouabain-hypertensive rats （OHR） and further elucidate the role of ouabain in the pathogenesis of hypertension. Methods Eighty male SD rats weighing 80-100 g were randomized equally into normal control and ouabain groups and treated with intraperitoneal injection of normal saline （1 ml/kg） and ouabain （27.8μg/kg） once daily, respectively. Systolic blood pressure （SBP） and body weight of the rats were recorded weekly. One week before sacrifice scheduled at weeks 2, 4, 6 and 8, respectively, the rats were individually housed in metabolic cages to determine food consumption twice. Blood and 24-hour urine samples were collected to measure serum and urine concentration of sodium, trace lithium and creatinine. Endogenous creatinine clearance rate （Ccr）, fractional excretions of sodium （FENa）, fractional excretions of lithium （FELi） and fractional reabsorption of sodium in the distal tubules （FDRNa） were calculated. Results The body weight and food intake between ouabain groups and control groups were comparable during the experiment （P〉0.05）. Blood pressure was also comparable in the two groups after 2 weeks （P〉0.05）. At week 4, however, blood pressure ofouabain group was significantly higher than that of the control group （P〈0.001） and increased in a dose-dependent manner. The SBP in ouabain group appeared to reach a plateau at week 7. Ccr and plasma sodium （PNa） were similar in the 2 groups during the experiment （P〉0.05）. FELi was significantly lower at weeks 2, 4 and 6 in ouabain group than in the control group （P〈0.01）, and FELi decrement in ouabain group was accompanied by reduced sodium excretion. FENa was significantly lower at week 4 in ouabain group than in the control group （P〈0.05）, but this difference was not significant in weeks 2 and 6 （P〉0.05）. At weeks 2, 4 and 6, ouabain group showed significantly lower FDRNa than the control group （P〈0.05）, suggesting the compensation of the distal nephron segments. After 8 weeks, FENa, FELi and FDRNa were similar between the two groups （P〉0.05）. Conclusions Ouabain can increase renal proximal tubule reabsorption of sodium and consequently decrease renal sodium excretion in OHR, which can contribute to alteration of the pressure-natriuresis relationship in OHR, and play an important role in the development and maintenance of hypertension of OHR.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2006年第10期1404-1407,共4页
Journal of Southern Medical University
基金
陕西省自然科学基金(2004C213)~~
关键词
哇巴因
高血压
肾脏钠转运
ouabain
hypertension
renal sodium transport
