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Effect of Aldose Reductase Inhibitor on Epithelial-mesenchymal Transition Induced by High Concentration of Glucose

Author: WangZhenShan
Tutor: OuYangDongSheng
School: Central South University
Course: Journal of Clinical Pharmacology
Keywords: Transdifferentiation High-sugar Aldose reductase Eucommia lignans Extracellular matrix
CLC: R965
Type: Master's thesis
Year: 2011
Downloads: 32
Quote: 0
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Abstract


Objective: To study the aldose reductase inhibitor epalrestat and gutta-percha lignans people of high glucose-induced renal tubular epithelial cells (HK-2) transdifferentiation and differentiated secretion of extracellular matrix. Its provide a theoretical basis for DN renal interstitial fibrosis prevention. Methods: HK-2 cells in vitro with high sugar, high sugar different concentration epalrestat, his high sugar concentration Eucommia lignans prime co-cultured for 48 h, using an inverted microscope to observe the changes in cell morphology; using real-time PCR of law determination reflects the turn indicators of differentiation alpha-smooth muscle muscles moving protein (α-SMA) and E-calcium sticky prime (E-cadherin) and reflect cell extracellular matrix secretion index collagen protein Ⅰ (Col Ⅰ) and fibronectin (FN) mRNA level; detected by Western blot alpha-SMA, E-cadherin, Col I, FN protein expression. Results: 1, high glucose-induced HK-2 cells form cobblestone cobblestone-like changes to the spindle long, aldose reductase inhibitors epalrestat and lignans can inhibit the high glucose-induced cell morphological changes; 2, alpha-SMA, E-cadherin, FN and Col I mRNA of glucose induced a time-concentration-dependent. A-SMA incubated in 50 mmol / L for 48 h increased the most obvious; FN, Col I increase by 20 mmol / L, 48 h most significant. 3, 1,10 μmol / L epalrestat his alpha-SMA mRNA were: 2.01 ± 0.28 and 0.93 ± 0.37, and the control group (2.38 ± 0.26) compared to reduced expression of the difference was statistically significant (P = 0.036 and P lt; 0.001); different concentrations of lignans can reduce alpha-SMA mRNA expression (low concentration: 2.19 ± 0.33; concentration: 1.93 ± 0.98; high concentration: 1.57 ± 0.94) compared with the control group, the difference was not statistically significant. 4, respectively, of 1umol / L 10umol / L epalrestat E-cadherin mRNA were: 2.71 ± 0.86 and 1.97 ± 0.67, and the control group (0.94 ± 0.42) compared to the increased expression of the difference was statistically significance (P = 0.007 and P = 0.033). 0.1mg / L, 1mg / L, 10mg / L lignans group of E-cadherin mRNA were: 1.77 ± 0.37,2.63 ± 0.41,3.61 ± 1.05, compared with control group, increased expression of the difference was statistically significant (P = 0.026, P lt; 0.001 and P = 0.004). 50 mmol / L mannitol significantly increased alpha-SMA (2.88 ± 1.30, P = 0.016), E-cadherin (2.00 ± 1.29), Col I (1.62 ± 0.33, P = 0.019). FN (2.10 ± 1.11, P = 0.036) mRNA expression levels, compared with the control group, the difference was statistically significant difference. Conclusion: 1, glucose in a dose-and time-dependent induction of HK-2 cells by the epithelial cell phenotype to the muscle fiber phenotype transformation, promotion of Col I, FN mRNA expression; 2 epalrestat and wood Lignans can antagonize the HK-2 cells in high glucose-induced transdifferentiation, epalrestat down HK-2 cells alpha-SMA mRNA expression, increase the expression of E-cadherin mRNA.

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