吡哆胺和替米沙坦对自发性高血压大鼠肾脏损害的影响

The effects of pyridoxamine and telmisartan on the renal damages in spontaneously hypertensive rats

目的观察单用及联用吡哆胺、替米沙坦对自发性高血压大鼠(SHR)肾脏损害的影响。方法 20周龄雄性SHR随机分为4组(每组12只):高血压组(蒸馏水)、替米沙坦组[6mg/(kg·d)]、吡哆胺组[200mg/(kg·d)]、联合组[替米沙坦6mg/(kg·d)+吡哆胺200mg/(kg·d)],连续灌胃给药。WKY大鼠为正常对照组,蒸馏水2mL/d灌胃。实验干预16周,测量干预前后的尾动脉收缩压,测定干预后24h尿微量白蛋白含量(免疫散射比浊法)及血清晚期糖基化终末产物(AGE)浓度(ELISA法),观察肾组织光镜下(HE、Masson染色)和透射电镜下的形态学改变,Westernblot法检测肾皮质转化生长因子β(TGF-β)水平。结果与正常对照组比较,高血压组血清AGE[(6.7±0.4)比(5.5±0.4)mg/L]、24h尿微量白蛋白[(404.9±91.8)比(20.2±3.1)mg]、肾皮质TGF-β含量[(1.6±0.2)比(0.8±0.3)]较高(均P<0.01);与高血压组比较,替米沙坦组、吡哆胺组、联合组24h尿微量白蛋白、血清AGE、肾皮质TGF-β较低(均P<0.01);与替米沙坦组比较,吡哆胺组、联合组的血清AGE[(5.6±0.9)、(5.2±0.6)比(6.0±0.5)mg/L]较低(P<0.05);与吡哆胺组比较,替米沙坦组、联合组干预后16周收缩压[(99.8±11.7)、(97.0±10.3)比(195.4±20.7)mmHg]较低(P<0.01)。高血压组肾小球基底膜不规则增厚,足突融合,毛细血管管腔狭窄,肾间质纤维性物质明显增多。结论吡哆胺和替米沙坦均可改善高血压大鼠早期肾损害,减少尿微量白蛋白,改善肾组织超微结构变化。吡哆胺对肾损害的改善作用可能与抑制体内AGE生成有关。

Objective To investigate the effects of pyridoxamine and telmisartan on the renal damages in of spontaneously hypertensive rats （SHR）. Methods SHR（male, 20 weeks of age） were randomly divided into 4 groups （n= 12） ： hypertension control group（given distilled water）, telmisartan group （ given 6 mg/kg telmisartan）, pyridoxamine group（given 200 mg/kg pyridoxamine） and combined group（given 6 mg/kg telmisartan and 200 mg/kg pyridoxamine）. Thirteen Wistar rats were served as controls, which were givengastric lavage with 2 mL of distilled water. This experiment was continued for 16 weeks. Tail systolic blood pressure （SBP） was measured be- fore and after the treatment. The levels of 24 h urinary albumin and serum advanced glycation end products（AGE） were determined by nephelometry and ELISA seperately. The kidney morphological changes were observed under light （H＆E or Masson＇s trichrome） and transmission electron microscopy. Expression of transforming growth factor-13 （TGF-13} in the renal cortex was determined by Western blot. Results Compared with control group, the levels of serum AGE [（6.74±0.4） vs （5.5±0.4） mg/L], 24 h urinary albumin [（404. 9±91.8） vs （20.2±3.1）mg] and the expression of TGF-13 in renal cortex [（1.6 ± 0.2） vs （0.8± 0.3）] were significantly increased in hypertension control group （P〈0.01 ）. And the levels of serum AGE, 24 h urinary albumin and the expression of TGF-13 in renal cortex were lower in telmisartan group, pyridoxamine group and combined group than in hypertension control group. Also the levels of serum AGE in pyridoxamine group （5.6±0.9） and combined group （5.2 ±0.6） were lower than those of telmisartan group （6.0±0.5）mg/L （P〈0.05）. After 16 weeks, SBP in telmisartan group （99.8±11.7） mm Hg and combined group （97.0± 10.3）mm Hg were lower than that of pyridoxamine group （195.4± 20.7）ram Hg （P〈0.01）. Histopathology showed irregular thickness of glomerulus, lumen occlusion in most of capillaries, glomerula-capsule adhesion and renal interstitial fibrosis in hypertension control group. Conclusion Pyridoxamine and telmisartan can decrease the urinary albumin, alleviate the renal ultrastructure damages in SHR, and result in significantly improving SHR early renal damages. The renal protective mechanism of pyridoxamine may be related to reducing the produce of AGE.