摘要
目的探究丹酚酸B(salvianolic acid B,Sal B)对肾间质纤维化Wnt/β-catenin信号通路关键组分的影响并初步探索其量效关系,为丹酚酸B在临床慢性肾病的治疗提供理论依据。方法将32只C57BL/6小鼠随机分为4组,每组8只:假手术组(Sham),模型组即单侧输尿管结扎组(unilateral ureteral obstruction,UUO),丹酚酸B(Sal B)高、低剂量组(25,6.25 mg·kg^(-1)·d^(-1))。术后第21天,采血,取肾。检测各组小鼠血清肌酐(serum creatinine,Scr)和血清尿素氮(blood urea nitrogen,Bun)的含量;HE和Masson染色光镜下观察肾间质的病理改变;Western Blot技术检测肾组织Col.Ⅰ、α-SMA、E-cad、TGF-β1、β-catenin和p-GSK3β蛋白表达水平。结果与Sham组比较,UUO组小鼠的血Scr、BUN均明显升高(P<0.05,P<0.01);与UUO组比较,Sal B低剂量组小鼠的血Scr、BUN无明显变化(P>0.05);Sal B高剂量组小鼠的血Scr、BUN有不同程度的降低,差异具有统计学意义(P<0.05)。HE、Masson染色结果,Sal B低、高剂量组小鼠肾间质病理变化明显轻于UUO组,评分显著减少(P<0.01)。肾组织Western Blot检测结果显示,与UUO组比较,Sal B低、高剂量组小鼠肾脏中Col.Ⅰ、α-SMA、TGF-β1的表达水平均有不同程度的下降(P<0.05,P<0.01),Sal B低剂量组E-cad的表达水平无明显变化,而Sal B高剂量组E-cad的表达水平则明显升高(P<0.01);β-catenin和p-GSK-3β蛋白表达水平均显著下降(P<0.01),且高剂量组各项指标较低剂量组下降更为明显(P<0.05,P<0.01)。结论丹酚酸B可能通过介导Wnt/β-catenin通路的关键组分,来调控Wnt/β-catenin信号通路,从而抑制UUO所致的小鼠肾间质纤维化。
Objective To investigate the effects of salvianolic acid B （SalB） on the key signaling factors of Wnt/ β-catenin signaling pathway in mice with renal tubulointerstitial fibrosis and to explore their dose-effect relationship, thus to provide evidence for the treatment of chronic kidney disease with salvianolic acid B. Methods A total of 32 C57/BL mice were randomly divided into four groups, sham operation group, unilateral ureteral obstruction （UUO） group, UUO＋ low-dose SalB group（6.25 mg·kg（-1）·d（-1））, and UUO＋ high-dose SalB group（25 mg·kg（-1）·d（-1）））. On the post-operative day 21, the kidney and blood were sampled. The contents of serum creatinine（Scr） and blood urea nitrogen（BUN） were measured by the corresponding kits. Renal interstitial pathological changes were observed after HE staining and Masson staining. Western blotting was employed to examine the protein expression of Col. I , a-SMA, E-cad, TGF-β, β -catenin and p-GSK3 β in the renal tissues. Results Compared with those of the sham operationgroup, the levels of BUN and Scr were significantly increased in UUO mice（P 〈 0.05）. Compared with those of UUO group, the levels of BUN and Scr had no significant changes in UUO＋ low-dose SalB group （P 〉 0.05）, but were decreased in various degrees in UUO＋ high-dose SalB group（P 〈 0.05）. HE staining and Masson staining showed that the renal interstitial pathological changes were obviously milder in both of UUO＋SalB groups than those in UUO group, and the pathological scores were significantly reduced （P 〈 0.001 ）. Compared with those of UUO group, the protein expression of Col. I , a-SMA and TGF-[M was decreased significantly in both UUO＋SalB groups, the protein expression of E-cad had no significant change in UUO＋ high-dose SalB group（P 〈 0.01 ）. The protein expression in both UUO＋SalB groups, Conclusion Salvianolic acid low-dose SalB group, but was increased obviously in UUO＋ of β -catenin and p-GSK3β was down-reg
作者
王曼
王新宇
陈叶香
孙帅军
蒋宝平
许立
WANG Man WANG Xinyu CHEN Yexiang SUN Shuaijun JIANG Baoping XU Li(Nanjing University of Chinese Medicine, Nanjing 210023 Jiangsu, China Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Medicine, Nanjing 210023 Jiangsu, China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2016年第5期602-607,共6页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
江苏省高校品牌专业建设工程资助(PPZY2015A070)
