阿魏酸哌嗪对单侧输尿管梗阻大鼠肾间质纤维化的保护作用

目的研究阿魏酸哌嗪对单侧榆尿管梗阻（UUO）大鼠肾间质纤维化是否有抑制作用及其肾脏保护作用的机制。方法75只SD大鼠设对照组（A组），结扎左侧输尿管（B组），分别给予阿魏酸哌嗪（C组），依那普利（D组），两者合用（E组）灌胃。术后第3、7和第14天测肾组织中羟脯氨酸含量，免疫组化测肾组织血管内皮生长因子（VEGF）、骨形成蛋白-7（BMP-7）、CD34表达（计算肾小管周围毛细血管指数，PCI）。结果各治疗组胶原含量明显减少，E组起效最早。UUO术后BMP-7、VEGF表达和PCI：B组逐渐减少，3个治疗组则明显上调。BMP-7、VEGF阳性面积和PCI与肾组织中胶原含量呈负相关（r=-0．68，-0．49，-0．52P〈0．01），VEGF阳性面积与PCI呈正相关（r=0．53，P〈0．01）。结论阿魏酸哌嗪通过上调肾组织中BMP-7、VEGF及PCI，抑制UUO大鼠肾间质纤维化，其疗效与依那普利相似，两药联合应用优于单独用药。

Renoprotective effects of piperazine ferulate in rats with interstitial fibrosis following unilateral ureteral obstruction

Objective To investigate the preventive effects of piperazine ferulate on the progression of renal interstitial fibrosis following unilateral ureteral obstruction(UUO) and its mechanism.Methods 75 Sprague-Dauley(SD) rats were randomly divided into the following 5 groups: Sham group(A group),UUO group(B group),piperazine ferulate(PF) group(C group),ACEI group(D group),PF+ACEI group(E group).After obstruction,PF,enalapril,or normal saline were administered separately by gavage once a day.On the 3rd day,7th day and 14th day after operation,rats were sacrificed.The levels of hydroxyproline were measured.The expressions of vascular endothelial growth factor(VEGF),bone morphogenetic protein-7(BMP-7) and CD34 were measured by immunohistochemistry.CD34,as the symbol of peritubular capillary was used to count the peritubular capillary index(PCI).Results Collagen contents were increased in all treatment groups with the maximum effect in E group.The expressions of BMP-7,VEGF and PCI were decreased in all treatment groups.The level of BMP-7 had a negative correlation with collagen contents.The drops of VEGF and PCI levels of all treatment groups were obviously delayed.PCI also had a negative correlation with the collagen contents.The level of VEGF had a negative correlation with the collagen contents and a positive correlation with PCI.Conclusion Piperazine ferulate administration greatly reduced the renal collagen contents,inhibited renal interstitial fibrosis of UUO rats,and delayed the reductions of VEGF and PTC levels after UUO.Its effects were similar to enalapril.Piperazine ferulate and enalapril administered together had a synergistic effect on inhibiting the progression of renal interstitial fibrosis following UUO.