水飞蓟宾对肾间质纤维化模型大鼠肾小管上皮-间充质转分化的影响Silybin on Renal Tubular Epithelial-mesenchymal Transdifferentiation in Renal Interstitial Fibrosis Rats
刘畅;朱春玲;严瑞;程全伟;
LIU Chang;ZHU Chunling;YAN Rui;CHENG Quanwei;Department of Kidney Medicine in the Affiliated Hospital of Guizhou Medical University;Department of Kidney Medicine of Guiyang First People's Hospital;
摘要(Abstract):
目的:探讨水飞蓟宾对肾间质纤维化模型大鼠肾小管上皮-间充质转分化(EMT)的影响。方法:将36只8周龄雄性SD大鼠均分为假手术组(S组)、模型组(U组)、治疗组[水飞蓟宾200 mg/(kg·d)](D组),U组及D组均采用单侧输尿管梗阻复制大鼠肾间质纤维化模型,D组大鼠于术后第1天使用水飞蓟宾灌胃至处死前[200 mg/(kg·d)],S组和U组注射等量生理盐水灌胃;各组大鼠分别于术后第7天、第14天处死6只大鼠,免疫组化染色和Western Blot观察观察Ski、E-钙粘蛋白(E-cadherin)、转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白、Ⅲ型胶原(col-Ⅲ)蛋白的表达,Pearson法分析Ski与TDI、TFI、TGF-β1、α-SMA、col-Ⅲ蛋白表达的相关性。结果:大鼠肾组织免疫组化染色和Western Blot结果显示,与S组比较,U组Ski、E-cadherin蛋白表达明显减少,TGF-β1、α-SMA、col-Ⅲ表达明显升高,第14天时变化更明显(P<0.05);与U组比较,D组大鼠肾组织中Ski、E-cadherin有所增加,但仅第14天差异有统计学意义(P<0.05),TGF-β1、α-SMA、col-Ⅲ显著降低,第14天组更为明显(P<0.05);Pearson相关分析显示,Ski表达与E-cadherin表达呈正相关,而与TGF-β1、α-SMA、col-Ⅲ呈负相关(P<0.05)。结论:水飞蓟宾可能通过Ski影响EMT的发生。
Objective: To investigate the effect of silybin on renal tubular epithelial-mesenchymal transdifferentiation( EMT). Methods: 36 8-week-old male Sprague-Dawley rats were divided into sham-operation group( group S),model group( group U) and treatment group [silybin 200 mg/( Kg·d) ]( group D). Rats in group U and group D were treated with unilateral ureteral obstruction to induce renal interstitial fibrosis,and the rats in group D were treated with silibin first days after the operation until the death of the stomach [200 mg/( kg·d) ]. Group S and group U were given the same amount of normal saline intragastric perfusion. Six rats in each group were killed on the 7 th and 14 th day after operation. Immunohistochemical staining and Western Blot were used to observe the expression of E-cadherin,TGF-β1,α-smooth muscle actin and Ⅲ collagen. Pearson analysis was used to analyze the correlation between Ski and the expression of TDI,TFI,TGF-β1,α-SMA and col-Ⅲ protein. Results: Immunohistochemical staining and Western Blot analysis of rat kidney showed that compared with group S,the expression of Ski and E-cadherin protein in group U was significantly reduced,the expression of TGF-β1,α-SMA and col-Ⅲ increased significantly,and the changes were more obvious on the fourteenth day( P < 0. 05). Compared with the group U,the renal tissue of rats in group D increased the level of Skio E-cadherin,but the difference was statistically significant only on the 14 th day( P < 0. 05). TGF-β1,α-SMA and col-Ⅲ decreased significantly,especially on the 14 th day( P <0. 05). Pearson correlation analysis showed that the expression of Ski was positively correlated with the expression of E-cadherin and negatively correlated with TGF-β1,α-SMA and col-Ⅲ( P < 0. 05). Conclusion: Silybin may influence the occurrence of EMT through Ski.
关键词(KeyWords):
肾间质纤维化;转化生长因子-β1;α-平滑肌肌动蛋白;肾小管上皮-间充质转分化;水飞蓟宾
renal interstitial fibrosis;renal tubular epithelial-mesenchymal transdifferentiation;transforming growth factor-β1;α-smooth muscle actin;silibinin
基金项目(Foundation): 贵州省科技厅社发攻关项目[黔科合SY字(2014)3021号];贵州省科技厅联合基金项目[黔科合LH字(2014)7124号];; 贵州省卫计委科技基金项目(gzwjki2014-1-007);; 贵阳市卫计委科学技术计划项目(2015筑卫科技合同字第018号)
作者(Author):
刘畅;朱春玲;严瑞;程全伟;
LIU Chang;ZHU Chunling;YAN Rui;CHENG Quanwei;Department of Kidney Medicine in the Affiliated Hospital of Guizhou Medical University;Department of Kidney Medicine of Guiyang First People's Hospital;
Email:
DOI: 10.19367/j.cnki.1000-2707.2018.04.005
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文章评论(Comment):
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- 肾间质纤维化
- 转化生长因子-β1
- α-平滑肌肌动蛋白
- 肾小管上皮-间充质转分化
- 水飞蓟宾
renal interstitial fibrosis - renal tubular epithelial-mesenchymal transdifferentiation
- transforming growth factor-β1
- α-smooth muscle actin
- silibinin
- 刘畅
- 朱春玲
- 严瑞
- 程全伟
LIU Chang- ZHU Chunling
- YAN Rui
- CHENG Quanwei
- Department of Kidney Medicine in the Affiliated Hospital of Guizhou Medical University
- Department of Kidney Medicine of Guiyang First People's Hospital
- 刘畅
- 朱春玲
- 严瑞
- 程全伟
LIU Chang- ZHU Chunling
- YAN Rui
- CHENG Quanwei
- Department of Kidney Medicine in the Affiliated Hospital of Guizhou Medical University
- Department of Kidney Medicine of Guiyang First People's Hospital