睾酮抑制高盐喂养下雄性大鼠血管内皮生长因子的表达和释放

Testosterone suppresses expression and release of vascular endothelial growth factor in rats under high-salt diet

目的 探讨不同水平睾酮对高盐饮食下雄性大鼠血管内皮生长因子的影响。方法 雄性Wistar大鼠32只随机分为4组：假手术组（Sham组），去势组（Cas组），去势后补充睾酮组（TC组），去势后补充睾酮和氟他胺组（FTC组）。每组8只。各组大鼠均以8%氯化钠高盐颗粒饲料喂养；Sham组施以假手术，Cas、TC及FTC组均施以去势手术。TC组及FTC组予丙酸睾酮2mg/kg、隔日1次皮下注射，FTC组同时予氟他胺1mg/kg、每日1次灌胃，持续8周。8周后采用酶联免疫吸附测定法（ELISA）测定各组血清中睾酮、血管内皮生长因子（VEGF）的浓度，实时定量PCR（RT-PCR）测定血管内皮中VEGF mRNA的表达水平。结果 （1）Cas组睾酮浓度[（0.26±0.02）μg/L] 与Sham组 [（3.15±0.54）μg/L]相比明显下降，而FTC组[（5.47±1.29）μg/L]、TC组[（2.80±0.30）ng/L]则明显升高（均P＜0.01）；（2）与Sham组的血清VEGF浓度[（20.837±13.823）ng/L]相比，Cas组[（47.246±19.733）ng/L，P＜0.01]和FTC组[（46.043±22.607）ng/L，P＜0.05]明显升高，TC组[（22.870±12.057）ng/L]则无明显差异（P＞0.05）；（3）与Sham组相比，Cas组和FTC组血管内皮细胞VEGF mRNA表达水平均显著降低（均P＜0.01），而TC组无显著差异（P＞0.05）。结论 高盐饮食下，睾酮水平增高抑制血管内皮生长因子的表达和释放。

Objective To determine the effect of different doses of testosterone on vascular endothelial growth factor （VEGF） in high-salt fed rats. Methods Thirty-two Wistar male rats were randomly assigned to 4 groups, sham-operation （Sham） group, castration （Cas） group, testosterone supplement after castration （TC） group, and flutamide-treated testosterone supplemented castrated （FTC） group, with 8 rats in each group. After all animals were fed with high-salt diet （8% NaCl） for 8 weeks, the rats of Sham group received a sham operation, while those in Cas, TC and FTC groups received surgical castration. Testosterone propionate （TP） was injected subcutaneously at 2mg/kg, once every 2 days in TC and FTC groups, and flutamide 1mg/（kg·d） was given intragastrically in FTC group, for 8 weeks after surgery. Serum levels of testosterone and VEGF were determined by enzyme-linked immunosorbent assay （ELISA）. Expression of VEGF mRNA in the blood samples were determined by real-time PCR （RT-PCR）. Results Serum levels of testosterone was obviously lower in Cas group, but significantly higher in TC and FTC groups when compared with Sham group [（0.26±0.02）, （2.80±0.30）, （5.47±1.29） vs （3.15±0.54）μg/ml, P〈0.01]. For serum level of VEGF, Cas FTC groups had obviously increased levels than Sham group [（47.246±19.733）, （46.043±22.607） vs （20.837±13.823） ng/L, P〈0.01, P〈0.05], but no difference was found between Sham group and TC group [ （22.870±12.057）ng/L, P〉0.05]. Cas group and FTC group had lower expression of VEGF mRNA compared with Sham group （P〈0.01）, but no difference with TC group（P〉0.05）. Conclusion Under high-salt diet, high level of testosterone suppresses the expression and release of VEGF.