大黄蒽醌提取物缓解小鼠肾组织纤维化作用的实验研究

Administration of Rhubarb extract attenuates renal fibrosis in mice

目的通过观察大黄蒽醌提取物抑制小鼠病变肾组织纤维化的作用,探讨大黄治疗肾脏病的作用机制。方法采用左侧输尿管结扎的方法建立单侧输尿管梗阻(UUO)雄性CD-1 小鼠动物模型。用形态学半定量方法评价组织学病变;酸水解-比色法测定肾组织胶原的含量; 蛋白印迹技术检测胶原α表达的水平。以α-平滑肌肌动蛋白(α-SMA)作为上皮细胞转分化的观察指标。结果大黄提取物(50 mg／kg体重)能够显著地减少肾间质的病变,降低肾组织中胶原的聚积,与对照组相比两者差异均有统计学意义。大黄提取物(25、50 mg／kg体重)能够降低病变肾组织中胶原α的表达水平及减少梗阻肾组织中α-SMA的表达,抑制上皮细胞转分化。结论大黄蒽醌化合物能够改善肾脏的纤维化,其作用可能与降低肾组织内胶原的沉积以及抑制上皮细胞转分化有关。

Objective To investigate the mechanism of Rhubarb in treating chronic kidney disease. Methods The animal model of renal disease was induced by unilateral ureteral obstruction （UUO） in CD-1 mice. The mice were divided into three groups： the sham, UUO, and UUO receiving Rhubarb extract treatment （12.5, 25, and 50 mg/kg body weight） daily. The morphological changes and content of total collagen from each group were examined at day 7 following UUO. Meanwhile, the de novo expression of a-smooth muscle actin （α-SMA）, and collagen Ⅰ in tissues from mice were assessed by Western blotting. Results Administration of Rhubarb extract markedly attenuated renal tissue injury, and decreased total collagen accumulation. The expression of α-SMA was suppressed dramatically in the mice receiving Rhubarb extract treatment （50 mg/kg body weight）. In addition, Rhubarb extract inhibited deposition of collagen Ⅰ significantly. Conclusion Rhubarb extract is a drug for amehoration of renal fibrosis of mice in vivo.