长期规律维生素D干预对自发性高血压大鼠肾素及其受体的影响

Influence of long-term regular vitamin D intervention on renin and renin receptor in spontaneously hypertensive rats

  • 摘要: 目的探讨维生素D长期规律用药对自发性高血压大鼠肾素及肾素受体的影响。方法自发性高血压大鼠20只随机分成两组(n=10),实验组给予维生素D33μg/kg溶于0.5mL丙二醇中腹腔注射,每周两次,总计12周;对照组以等容积的丙二醇腹腔注射。每周以无创测压法监测大鼠血压变化。干预前后收集血清和尿液检测25-羟基维生素D325-(OH)D3、钙、肾素和24h尿白蛋白的浓度;RT-PCR法检测实验组和对照组肾脏维生素D受体(VDR)、肾素及肾素受体mRNA的表达水平;免疫组化观察肾脏和心脏肾素受体的分布部位及分布强度;HE染色观察大鼠病理改变。结果与对照组相比,实验组收缩压降低(156±9)比(170±8)mm Hg,P<0.05;血25(OH)D3和钙浓度升高分别(117.5±13.7)比(68.2±12.2)μg/L,(2.34±0.10)比(2.15±0.16)mmol/L,P<0.05,肾素(232.7±18.8)比(263.2±32.8)ng/L,P<0.05和24h尿蛋白(0.50±0.36)比(0.83±0.44)mg,P<0.05水平减低。RT-PCR结果显示,实验组大鼠肾脏中VDR mRNA的表达量高于对照组(0.595±0.053)比(0.461±0.048),P<0.05;肾素mRNA表达水平低于对照组(0.133±0.007)比(0.316±0.012),P<0.05;两组间肾素受体mRNA表达差异无统计学意义(P>0.05)。免疫组化结果显示,肾素受体在心、肾和血管等分布广泛,肾素受体累积光密度值在两组表达差异无统计学意义(P>0.05)。HE染色显示,实验组高血压病理改变明显轻于对照组。结论维生素D能够抑制高血压大鼠肾素基因的表达,减轻高血压肾损害,但对肾素受体的调节作用不明显。

     

    Abstract: Objective To explore the influence of long-term regular vitamin D intervention on renin and renin receptor in spontaneously hypertensive rats. Methods A total of 20spontaneously hypertensive rats were randomly divided into two groups(n=10). The experimental group received 3μg/kg vitamin D3dissolved in 0.5mL propylene glycol by intraperitoneal injection(twice a week)for 12weeks,and the control group was given equal volume of propylene glycol alone. Blood pressure was measured every week. The level of serum 25-hydroxy vitamin D325-(OH)D3,calcium,renin and 24hours urinary albumin were determined. The mRNA expression of vitamin D receptor(VDR),renin and renin receptor in kidney of the two groups were detected by RT-PCR. Distribution of renin receptor and pathological changes in kidney and heart were examined by immunohistochemical and HE staining.Results Compared with those of control group,the systolic blood pressure(156±9)vs(170±8)mm Hg,P<0.05,serum renin(232.7±18.8)vs(263.2±32.8)ng/L,P<0.05and 24hours urinary albumin (0.50±0.36)vs(0.83±0.44)mg,P<0.05of experimental group were lower,while the serum concentration of25-(OH)D3and calcium in experimental group were higher(117.5±13.7)vs(68.2±12.2)μg/L,(2.34±0.10)vs(2.15±0.16)mmol/L,all P<0.05. After the treatment with vitamin D,the VDR mRNA expression was significantly increased(0.595±0.053)vs(0.461±0.048),P<0.05,but the renin mRNA expression in kidney wasmarkedly decreased(0.133±0.007)vs(0.316±0.012),P<0.05. Renin receptor was widely distributed in heart,vessels and kidney,but there was no statistic significant difference of the receptor expression between the two groups(P>0.05). HE staining showed that hypertensive pathological changes in control group was more obvious than that in experimental group. Conclusion Treatmemt with vitamin D could inhibit renin expression and attenuate the damage of kidney in spontaneously hypertensive rats,but exert no effects on renin receptor expression in the kidney.

     

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