吡格列酮对糖尿病大鼠肾脏组织中干细胞标志物表达的影响Effect of Pioglitazone on the Expression of Stem Cell Marker in Kidney Tissue of Diabetic Rats
张业;严瑞;李华;刘畅;周兴艳;朱春玲;
ZHANG Ye;YAN Rui;LI Hua;LIU Chang;ZHOU Xingyan;ZHU Chunling;Guizhou Medical University;Department of Nephrology,Affiliated Hospital of Guizhou Medical University;
摘要(Abstract):
目的:探讨过氧化物酶增殖物激活受体γ(PPARγ)的特异性激动剂吡格列酮(PIO)对糖尿病大鼠(DM)肾脏组织中干细胞标志物CD24、CD133表达的影响。方法:将24只大鼠均分为正常对照组(NC组)、糖尿病组(DM组)和吡格列酮喂养组(DP组),DM组和DP组用链脲佐菌素(STZ)复制DM大鼠模型,造模成功后DP组大鼠用PIO灌胃8周;3组大鼠饲养至16周时处死取肾组织,采用Western blot法检测肾组织中CD24、CD133、E钙黏蛋白(E-cadherin)、α-平滑肌肌动蛋白(α-SMA)及Fibronectin蛋白的表达;qRT-PCR检测肾组织中CD24和CD133 mRNA的表达。结果:与NC组大鼠比较,DM组大鼠肾组织CD24、CD133蛋白及mRNA、Fibronectin、α-SMA蛋白表达增多,E-cadherin表达减少,差异有统计学意义(P<0.05);与DM组比较,DP组大鼠肾组织CD24、CD133蛋白及mRNA、Fibronectin、α-SMA蛋白表达均减少,E-cadherin表达增多,差异有统计学意义(P<0.05)。结论:吡格列酮可能通过抑制EMT的发生,影响糖尿病肾组织纤维化程度及CD24、CD133的表达。
Objective: To investigate the effect of peroxidase-activated agonist gamma(PPARγ)-specific ligand pioglitazone(PIO) on the expression of stem cell marker CD24 CD133 and its mechanism in diabetic rats(DM). Methods: 24 rats were divided into normal control group(NC group), diabetic group(DM group), and Pioglitazone-fed group(DP group). DM rat model of DM group and DP group was replicated with streptozotocin(STZ). After successful modeling, DP group was perfused with PIO for 8 weeks. After 16 weeks, the three groups of rats were put to death for renal tissue; Western blot was used to detect the expression of CD24, CD133, E-cadherin, α-SMA and Fibronectin protein in renal tissue. Meanwhile, the expression of CD24 and CD133 mRNA changes in renal tissues were detected by qRT-PCR. Results: Compared with NC group, the expression of CD24, CD133 protein and mRNA, α-SMA and Fibronectin protein in DM group increased, and the expression of E-cadherin protein decreased, difference was statistically significant(P<0.05). Compared with DM group, the expression of CD24, CD133 protein and mRNA, α-SMA and Fibronectin protein in DP group decreased, and the expression of E-cadherin increased, difference was statistically significant(P<0.05). Conclusion: Pioglitazone may affect the degree of fibrosis and the expression of CD24 and CD133 in diabetic kidney by inhibiting the occurrence of EMT.
关键词(KeyWords):
糖尿病肾病;肾脏纤维化;上皮细胞向间质细胞转化;肾脏干细胞;CD24;CD133;吡格列酮
diabetic nephropathy;renal fibrosis;epithelial mesenchymal transformation;kidney stem cell;CD24;CD133;pioglitazone
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(gzwjkj2014-1-007)
作者(Author):
张业;严瑞;李华;刘畅;周兴艳;朱春玲;
ZHANG Ye;YAN Rui;LI Hua;LIU Chang;ZHOU Xingyan;ZHU Chunling;Guizhou Medical University;Department of Nephrology,Affiliated Hospital of Guizhou Medical University;
Email:
DOI: 10.19367/j.cnki.1000-2707.2019.05.012
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- 糖尿病肾病
- 肾脏纤维化
- 上皮细胞向间质细胞转化
- 肾脏干细胞
- CD24
- CD133
- 吡格列酮
diabetic nephropathy - renal fibrosis
- epithelial mesenchymal transformation
- kidney stem cell
- CD24
- CD133
- pioglitazone
- 张业
- 严瑞
- 李华
- 刘畅
- 周兴艳
- 朱春玲
ZHANG Ye- YAN Rui
- LI Hua
- LIU Chang
- ZHOU Xingyan
- ZHU Chunling
- Guizhou Medical University
- Department of Nephrology
- Affiliated Hospital of Guizhou Medical University
- 张业
- 严瑞
- 李华
- 刘畅
- 周兴艳
- 朱春玲
ZHANG Ye- YAN Rui
- LI Hua
- LIU Chang
- ZHOU Xingyan
- ZHU Chunling
- Guizhou Medical University
- Department of Nephrology
- Affiliated Hospital of Guizhou Medical University