黄芪当归合剂肾脏保护作用的有效部位筛选

Screening effective parts of combination of Astragali Radix and Angelicae Sinensis Radix (A&A) for its renoprotective effects

目的:以肾间质纤维化模型大鼠的肾功能及肾小管间质损伤指数改善为药理活性指标,对黄芪当归合剂(A&A)进行分离和筛选,获得其肾脏保护作用的药物有效部位。方法:应用溶剂法和色谱法逐级对A&A进行追踪分离,分别获得11个不同部位。同时将Wistar大鼠随机分为假手术组、单侧输尿管梗阻(UUO)模型组、A&A组及不同部位治疗组。灌胃给药后观察A&A各部位对UUO大鼠肾损伤的疗效。治疗10 d后经腹主动脉取血检测血清肌酐(Scr)和尿素(Urea)水平;同时观察梗阻侧肾脏的病理变化,并对肾间质细胞浸润、肾小管萎缩和肾间质纤维化等病理损伤的程度(PI-Ⅰ)进行半定量评分,以PI-Ⅰ改善作为主要疗效、肾功能改善作为次要疗效,筛选获得具有最佳药理活性的有效部位。结果:在溶剂法分离获得的7个不同极性部位中,组分I和IC均具有改善肾功能、减轻肾小管间质损伤的疗效,其肾脏保护作用与A&A疗效相近;而色谱法分离IC得到的4个部位对Scr,Urea及PI-I均无改善作用。结论:在UUO大鼠模型中,源自复方中药A&A的组分I和IC具有与原方剂相似,具有抑制肾间质纤维化的作用,可确认为A&A肾脏保护作用的有效部位。

Objective： The decoction of Astragali Radix and Angelicae Sinensis Radix（A＆A） has shown antifibrotic effects in rats with unilateral ureteral obstruction（UUO）.The aim of this study was to track the effective parts of A＆A for its renoprotective effects,according to the improvement of renal function and renal tubulointerstitial damage.Method： A＆A was sequentially extracted by using different solvents for three times and eleven different parts were gained.Wistar rats were randomly divided into Sham,UUO and the treatment groups with A＆A or each part of A＆A.After administration of A＆A or its parts for 10 days,the levels of serum creatinin（Scr） and urea were measured.The morphological changes of kidneys were also semi-quantitatively analyzed by HE,Masson stained tissue sections,which including interstitial cell infiltration,tubular atrophy and interstitial fibrosis.Result： The levels of Scr,urea were significantly increased,accompanied with severe renal damage in rats with UUO.As same as A＆A,the part I in the first extraction and part IC in the second extraction were all shown to decrease the levels of Scr and urea and the index of renal interstitial damage.However,the following 4 parts extracted from IC in the third extraction were shown no effect on the above indexes.Conclusion： The extract part I and part IC could be considered as the predominant parts of A＆A for its renoprotective effects,due to their improvement of renal damage in interstitial nephropathy.