黄芪对单侧输尿管梗阻大鼠肾间质纤维化的作用研究

STUDY ON THE EFFECT OF ASTRAGALUS MONGHOLICUS ON RENAL FIBROSIS IN SD RATS WITH UNILATERAL URETERAL OBSTRUCTION

[目的]观察黄芪(AM)对单侧输尿管梗阻(UUO)所致大鼠肾小管间质纤维化的影响,初步探讨其抗纤维化分子作用机制。[方法]48只SD大鼠随机分为假手术(Sham)、UUO组和UUO+黄芪治疗组(AM)、UUO+氯沙坦治疗组(ARB)。在造模后7、14d处死动物,观察肾脏病理改变。采用免疫组化方法检测肾组织中纤连蛋白(FN)和胶原Ⅰ(colⅠ)表达。用实时荧光定量RT-PCR检测大鼠FNmRNA和colⅠmRNA表达量。[结果]与假手术组相比,UUO术后大鼠肾脏病理损害进行性加重,FN和colⅠ表达显著增高(P﹤0.05);AM治疗后可明显减轻UUO大鼠肾组织的肾小管损伤及肾间质纤维化,使UUO大鼠肾组织中高表达的FN和colⅠ明显降低(P﹤0.05),与ARB作用相似(P﹥0.05)。[结论]黄芪可能通过抑制肾小管间质细胞外基质积聚,减轻和改善UUO大鼠肾间质纤维化。

[Objective] To study the effect of Astragalus mongholicus （AM） on renal fibrosis in SD rats with Unilateral Ureteral Obstruction （UUO）, and to explore the molecular mechanisms of AM of anti-fibrosis. [Methods] 48 Sprague-Dawley rats were randomly divided into 4 groups： sham-operation group （Sham）, the UUO group （UUO）, UUO ＋ AM group（AM） and UUO ＋ Losartan group （ARB）. At 7, 14 days after UUO, the dynamic histological changes of renal interstitial tissues were observed. The expression of fibronectin （FN） and collagen I （col I ） were measured by immunohistochemistry staining sections. The mRNA of FN and col I were reversed transcribed and quantified by real-time PCR. [Results] Renal damage was exacerbated and the expression of FN and col I were all significantly increased in UUO group compared with those of Sham group （P 〈 0.05） at each time point. Tubular lesions and interstitial fibrosis were alleviated, and up-regulations of expressions of FN and col I were significantly suppressed by AM treatment （P 〈 0.05）, and there were no significant difference between AM and ARB groups （P 〉 0.05）. [Conclusion] AM can ameliorate renal interstitial fibrosis induced by UUO in rats. The mechanisms of its antifibrosis effects may be related with the suppression of the accumulation of extra cellular matrix.