全反式维甲酸对5/6肾大部切除大鼠肾素-血管紧张素系统的影响

目的 观察全反式维甲酸（atRA）对残余肾肾素-血管紧张素系统（RAS）的影响。 方法 采用5/6肾大部切除大鼠模型，分别给予5 mg·kg-1·d-1（n＝8）、10 mg·kg-1·d-1（n＝8）、20 mg·kg-1·d-1（n＝8）的atRA灌胃。单纯肾大部切除非干预组（NX组，n＝8）和假手术组（sham组，n＝8）为对照。放射免疫法检测大鼠肾皮质肾素、血管紧张素水平。Western印迹检测肾组织血管紧张素1型受体（AT1R）水平。实时定量PCR方法检测激活蛋白1（AP-1）亚单位c-jun和c-fos mRNA的表达水平。 结果 atRA 灌胃10周时， 3种剂量atRA组收缩压明显低于NX组（P < 0.05），但不同剂量atRA组间差异无统计学意义。NX组大鼠肾皮质肾素和血管紧张素Ⅱ水平均显著高于sham组（P < 0.05）。atRA治疗组肾皮质肾素和血管紧张素Ⅱ水平均显著低于NX组，其中20 mg·kg-1·d-1组二者水平显著低于其他两个剂量组。atRA抑制残肾皮质AT1R表达约30％，而20 mg·kg-1·d-1剂量组AT1R表达水平最低。atRA组AP-1亚基c-jun和c-fos mRNA表达显著低于NX组（P < 0.05）。 结论 atRA能明显抑制5/6肾大部切除大鼠肾皮质RAS主要成分的高表达。

All-tram retinoic acid markedly inhibits over-excitement of renin-angiotensin system in 5/6 renal ablation rats

Objective To investigate the effect of all-trans retinoic acid (atRA) on the renin-angiotensin system (RAS) in 5/6 renal ablation model. Methods AtRA was administered to 5/6 renal ablation rats by three dosages: 5 mg·kg-1·d-1 (n=8), 10 mg·kg-1d-1 (n=8) and 20 mg·kg-1 d-1 (n=8) and vehicle (vehicle group, n=8) for 10 weeks. Healthy rats consisted of shamoperation group (n =8). The level of renin and angiotensin Ⅱ in renal tissues were measured by radioimmunoassary. The level of angiotensin type 1 receptor (AT1R) in remnant renal cortex was measured by Western blot. The mRNA expression levels of two subunits of activative protein 1(AP-1),c-jun and c-fos was quantitated by real-time PCR. Results After 10 weeks of atRA treatment by gavarge, artery blood pressure decreased (P＜0.05). AtRA reduced the levels of renin (P＜0.05) and angiotensin Ⅱ (P＜0.05) in kidney and down-regulated the expression of AT1R protein in renal cortex. Larger dose of atRA (20 mg·kg-1·d-1) performed higher activity in inhibiting renin and AT1R. Compared with vehicle group, atRA could significantly inhibit the expression of renal c-jun and c-fos mRNA (P＜0.05). Conclusion atRA can decrease the over-expression of main components of RAS.