丹参酚酸B对实验性肾间质纤维化大鼠的保护作用及其机制

Protection and Mechanisms of Salvianolic-acid B on Experimental Renal Interstitial Fibrosis in Rats

目的:探讨丹参酚酸B(Salvianolic-acid B,SA-B)对单侧输尿管结扎(Unilateral Ureteral Obstruction,UUO)所致的肾纤维化大鼠的作用和机制。方法:雄性SD大鼠18只,随机分成3组,每组6只。单侧输尿管结扎建立肾间质纤维化动物模型。SA-B治疗2 w后,光镜、电镜下观察肾组织病理改变;Western blot和免疫组化法检测肾组织α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)和E-钙依赖性黏附素(E-cadherin,E-cad)的表达。结果:与假手术组比较,模型组大鼠光镜下观察肾间质中大量细胞浸润,部分小管扩张,同时部分小管萎缩;电镜下观察肾小管上皮细胞结构松散,混浊,肾间质显著增宽,间质细胞增多;α-SMA蛋白表达显著增加(P<0.01),E-cad蛋白表达显著下降(P<0.01)。SA-B干预后,上述病理改变显著轻于模型组,α-SMA蛋白表达显著下降(P<0.05),E-cad蛋白表达略有上升(P>0.05)。结论:SA-B通过抑制α-SMA蛋白表达,维持上皮细胞的表型,延缓肾纤维化的发生。

Objective：To investigate the effect and mechanism of salvianolic acid B（SA-B） on renal interstitial fibrosis in rats induced by unilateral ureteral obstruction（UUO）.Methods：18 male SD rats were randomly divided into 3 groups,6 in each group.After the models were established,the rats were treated with SA-B for 2 weeks.Then their renal pdthology were exmined by hight microscope and electron microscopy Protein expression levels of α-smooth muscle actin（α-SMA） and E-cadherin（E-cad） in the obstructed kidney were analyzed by Western blot and Biochemistry assay.Results：Pathological examination of the kidney in model group showed tubules lumen widened and many inflammatory cells infiltrated,a part of renal tubule expanded and part of them atrophied.The tubular epithelial cells were karyorrhexis or karyolysis,some tubulars were atrophy.The protein expression of α-SMA were significantly up-regulated（P0.01） and E-cad were significantly down-regulated（P0.01） in the model group.After intervention with SA-B,the renal pathological status in the treatment group was significantly improved,the expression of α-SMA were significantly down-regulated（P0.05）,but E-cad only a little up-regulated（P0.05）.Conclusion：SA-B could antagonize renal interstitial fibrosis mainly by maintaining epithelial phenotype,inhibiting the protein of α-SMA which is the principal effect cells that are responsible for the progressive kidney fibrosis.