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吡格列酮对高糖诱导的大鼠肾小管上皮细胞-间充质细胞转分化的影响及机制研究
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| 篇名： | 吡格列酮对高糖诱导的大鼠肾小管上皮细胞-间充质细胞转分化的影响及机制研究 |
| TITLE： | Effects and Mechanism Study of Pioglitazone on High Glucose-induced Epithelial-mesenchymal Transition in Renal Tubular Epithelial Cells of Rat |
| 摘要： | 目的：探讨吡格列酮（PIO）对高糖诱导的大鼠肾小管上皮细胞-间充质细胞转分化（EMT）的影响及可能机制，为防治糖尿病肾病提供理论依据及新靶点。方法：将大鼠肾小管细胞NRK-52E随机分为对照组（5.5mmol/L葡萄糖）、高糖组（30mmol/L葡萄糖）、PIO干预组（30mmol/L葡萄糖+5.0μmol/LPIO）、GW9662干预组（30mmol/L葡萄糖+5.0μmol/LPIO+5.0μmol/L特异性拮抗剂GW9662）。前3组细胞分别在培养6、12、24、48h时进行动态检测，GW9662干预组细胞在培养48h时进行检测。采用Real-timePCR法检测细胞中第10号染色体缺失的磷酸酶和张力蛋白同源基因（PTEN）、过氧化物酶体增殖物激活受体γ（PPARγ）mRNA的表达水平；采用Westernblotting法检测细胞中PTEN、PPARγ、α-平滑肌肌动蛋白（α-SMA）、上皮钙黏素（E-cadherin）的表达以及磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B（AKT）信号通路的变化。结果：随培养时间的延长，与正常组比较，高糖组细胞中PPARγ、PTENmRNA及蛋白（除PPARγ6h外）表达水平均显著降低，α-SMA、p-AKT（Thr308）蛋白表达水平均显著升高，E-cadherin蛋白表达水平显著降低（P＜0.05），且呈时间依赖趋势；与高糖组比较，PIO组细胞中PPARγ（除6h时的蛋白表达外）、PTEN的mRNA及蛋白表达水平均显著升高，α-SMA、p-AKT（Thr308（）除6h外）蛋白表达水平均显著降低，E-cadherin蛋白表达水平显著增高（P＜0.05），且呈时间依赖趋势。与高糖组比较，GW9662干预组细胞PTEN、PPARγmRNA及蛋白表达水平，α-SMA、E-cadherin、p-AKT（Thr308）蛋白表达水平的差异均无统计学意义，PIO的作用效应被PPARγ拮抗剂GW9662阻断。结论：在高糖条件下PIO可能是通过激活PPARγ而实现对PTEN表达的调控，使PI3K/AKT信号通路受到抑制，进而抑制肾小管上皮细胞EMT的发生。 |
| ABSTRACT： | OBJECTIVE：To investigate the effects o f pioglitazone （PIO）on high glucose-induced epithelial-mesenchymal transition（EMT）in renal tubular epithelial cells of rat and its possible mechanism ，and to provide theoretic reference and new target for the prevention and treatment of diabetic nephropathy. METHODS ：The rat renal tubular epithelial NRK- 52E cells were randomly divided into control group （5.5 mmol/L glucose ），high-glucose group （30 mmol/L glucose ），PIO intervention group （30 mmol/L glucose+ 5.0 μmol/L PIO），GW9662 intervention group （30 mmol/L glucose+ 5.0 μmol/L PIO+5.0 μmol/L specific anta- gonist GW 9662）. The cells of the first 3 groups were detected at 6，12，24，48 h of culture ，while those in GW 9662 intervention group were detected at 48 h of culture. mRNA expression of PTEN and PPARγ were detected by real-time PCR. The protein expression of PTEN ，PPARγ，α-SMA and E-cadherin as well as the changes of PI 3K/AKT signaling pathway were determined by Western blotting assay. RESULTS ：With the extension of culture time ，compared with control group ，the mRNA and protein expression of PPARγ（except for protein expression at 6 h）and PTEN in high-glucose group reduced significantly ，while the protein expression of α-SMA and p-AKT （Thr308）increased significantly ，and the protein expression of E-cadherin reduced significantly （P＜0.05），showing time-dependent trend. Compared with high-glucose group ，the mRNA and the protein expression （except for 6 h） of PPAR γ and PTEN were increased significantly in PIO intervention group ， while the protein expression of α-SMA and p-AKT （Thr308） were decreased significantly，and the protein expression of E-cadherin wasincreased significantly （P＜0.05）， showing time-dependent trend. There was no statistical significance in mRNA and protein expression of PPAR γ and PTEN，protein expression of E-cadherin ，α-SMA and p-AKT （Thr308） between GW 9662 intervention group and high-glucose group ；the effect of PIO was blocked by PPAR γ antagonist GW9662. CONCLUSIONS ：PIO may up-regulate the expression of PTEN by activating PPARγ，inhibit PI 3K/AKT signaling pathway so as to inhibit the occurrence of EMT of renal tubular epithelial cells . |
| 期刊： | 2020年第31卷第16期 |
| 作者： | 孙兰，张帆，石明隽，田平平，郭兵 |
| AUTHORS： | SUN Lan，ZHANG Fan，SHI Mingjun ，TIAN Pingping ，GUO Bing |
| 关键字： | 吡格列酮；肾小管上皮细胞；过氧化物酶体增殖物激活受体γ；第10号染色体缺失的磷酸酶和张力蛋白同源基因；磷脂酰 |
| KEYWORDS： | Pioglitazone；Renal tubular epithelial cell ；PPARγ；PTEN；PI3K/AKT signaling pathway ；Epithelial-mesenchymal |
| 阅读数： | 245 次 |
| 本月下载数： | 4 次 |
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