Injury human renal tubular epithelial cell induced by vancomycin and its expression of Smad4
Objective To study the injury of human renal tubular epithelial cells(HK-2)induced by vancomycin and the expression of Smad4,and to explore the potential mechanism of action.Methods HK-2 cells were treated with vancomycin solution at different final concentrations(0,1,2,3,4,and 5 mmol/L)for 24 h,and the effect of vancomycin on cell morphology was observed under microscope.The protein levels of Smad4,Bax,and Bcl-2 were detected by Western blotting.The apoptosis of HK-2 cells was detected by TUNEL method.The activity of HK-2 cells was detected by CCK8 method to study the toxic effect of vancomycin on kidney.Smad4 overexpression plasmid was constructed,and the effect of Smad4 overexpression on vancomycin-induced HK-2 cell damage was detected by CCK8 assay and TUNEL assay.Results Compared with the control group,with the increase of vancomycin concentration,the number of HK-2 cells was gradually deformed and decreased.The cell viability was significantly decreased and the apoptosis rate was significantly increased(P<0.05,0.01).Compared with the control group,the expressions of pro-apoptotic protein Bax were significantly increased,while the expressions of anti-apoptotic proteins Smad4 and Bcl-2 were significantly decreased(P<0.05,0.01,0.001).After overexpression of Smad4,vancomycin-induced HK-2 cell viability was significantly increased,and apoptosis rate was significantly decreased(P<0.05,0.001).Conclusion Vancomycin can induce the injury of human renal tubular epithelial cells,and its mechanism may be closely related to the regulation of Smad4 protein degradation.
NETL
NSTL
万方数据
维普
