黄芪甲苷对肾性高血压大鼠肾脏的保护作用及机制研究  

Protective Effect and Mechanism of Astragaloside on Kidney of Rats with Renovascular Hypertension

作　　者：何自育 杨育红[1] 王洪新[1] 

机构地区：[1]辽宁医学院基础医学院,辽宁锦州121001 [2]锦州市解放军第二0五医院肾病风湿血液科,辽宁锦州121000

出　　处：《中药新药与临床药理》2014年第4期446-450,共5页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金(30973898/C190702);辽宁省教育厅优秀人才基金(2008RC33)

摘　　要：目的观察黄芪甲苷对肾性高血压大鼠的保护作用及其机制。方法将60只SD雄性大鼠按照经典两肾一夹(2-kidney-1-clip,2K1C)型肾性高血压大鼠模型方法建模,将成模大鼠随机分为模型组,黄芪甲苷低、高剂量组,依那普利组,同时设假手术组。各组大鼠灌胃给药8周后,观察各组大鼠血压及肾脏组织学变化,血清超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malonaldehyde,MDA)、一氧化氮(nitric oxide,NO)和诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)水平以及肾脏组织Cu-Zn-SODmRNA、iNOSmRNA表达情况。结果 (1)应用黄芪甲苷干预后大鼠尾动脉收缩压明显降低,尤其黄芪甲苷高剂量组收缩压与依那普利组相仿;光镜下可见模型组肾小球毛细血管塌陷,肾小球萎缩、硬化、坏死,肾间质可见大量炎症细胞和红细胞浸润等;黄芪甲苷高剂量组、依那普利组未见肾小球萎缩、坏死,肾间质仍偶见炎症细胞浸润。(2)与假手术组比较,模型组血清SOD、NO和iNOS显著降低,MDA显著升高(P约0.01);与模型组比较,黄芪甲苷低、高剂量组血清SOD、NO和iNOS显著升高,MDA显著降低(P约0.05)。黄芪甲苷高剂量组血清SOD显著低于依那普利组,血清MDA、NO和iNOS显著高于依那普利组(P约0.05)。(3)黄芪甲苷低、高剂量组大鼠肾脏组织Cu-Zn-SODmRNA、iNOSmRNA表达均显著升高(P约0.05),其中黄芪甲苷高剂量组高于低剂量组(P约0.05),表现出良好的剂量关系。结论黄芪甲苷能够有效降低肾性高血压大鼠肾脏损伤,其机制可能与抗氧化应激和调节血管收缩功能有关。Objective To observe the protective effect and mechanism of astragaloside on kidney of renovascular hypertension. Methods renovascular hypertension. And then the Sixty male SD rats were given two-kidney one-clip treatment rats with to induce modeled rats were randomly divided into model group, low-dose astragaloside group, high-dose astragaloside group and enalapril group. Moreover, sham operation group was built. Rats in each group were given intragastric administration for 8 weeks. After treatment, the changes of serum superoxide dismatase （SOD） , malonaldehyde （ NDA ）, nitric oxide （ NO ） and inducible NO syntha se （iNOS） levels, expression levels of Cu-Zn-SOD mRNA and iNOS mRNA, and the histology of renal tissue were observed. Results （1）In the model group, histological changes of glomerular capillary collapse, glomerular atrophy, sclerosis and necrosis, amount of inflammatory cells and red blood cells infiltration in the renal interstitium were found. In high-dose astragaloside group and enalapril group, glomerular atrophy and necrosis were alleviated, and inflammatory cells infiltration in the renal interstitium was occasionally seen. （2）Serum SOD, NO and iNOS levels were decreased, and MDA level wasincreased significantly in the model group （P 〈 0.01 ）. Serum SOD, NO and iNOS levels were increased, and MDA was decreased significantly in low- and high-dose astragaloside groups （P 〈 0.05）. High-dose astragaloside group had lower SOD level and higher MDA, NO and iNOS levels than enalapril group（P 〈 0.05）. （3）Cu-Zn-SOD mRNA and iNOS mRNA expression levels were increased in low-and high-dose astragaloside group （P 〈 0.05 compared with those in the model group）, and high-dose astragaloside had the highest expression levels （P 〈 0.05） . Conclusion Astragaloside can effectively relieve the kidney damage of rats with renovascular hypertension, and its mechanism may be related with counteracting oxidative stress and regulating vasoconstriction.

关 键 词：黄芪甲苷 肾性高血压 氧化应激 机制 

分 类 号：R285.5[医药卫生—中药学]