柯里拉京通过转录因子7影响足细胞氧化应激及凋亡缓解糖尿病肾病的研究OA

Objective To explore the possible mechanisms through which corilagin affects high-glucose-induced oxidative stress and apoptosis in podocytes to alleviate diabetic nephropathy(DN).Methods MPC5 cells in the logarithmic growth phase were divided into 5 groups:control group(5 mmol·L-1 glucose),model group(30 mmol·L-1 glucose),corilagin group(30 mmol·L-1 glucose plus 50 μM corilagin treatment),corilagin+pcDNA3.1 group(30 mmol·L-1 glucose plus corilagin 50 μM treatment after transfection with pcDNA3.1),and corilagin+pcDNA3.1-transcription factor 7(TCF7)group(30 mmol·L-1 glucose plus corilagin 50 μM treatment after transfection with pcDNA3.1-TCF7).Real-time quantitative polymerase chain reaction(qPCR)was used to detect the expression of long non-coding RNA(LncRNA)TCF7;terminal deoxynucleotidyl transferase dUTP nick-end labeling was employed to assess the apoptosis rate;Western blot was used to analyze the expression of Cleaved caspase-9,Cleaved caspase-3,and proteins related to the glycogen synthase kinase 3 beta(GSK3β)/nuclear factor erythroid-2-related factor2(Nrf2)signaling pathway;2′,7′-dichlorofluorescein diacetate fluorescent probe was utilized to measure reactive oxygen species(ROS)levels;and immunofluorescence was used to examine the expression of nephrin and podocin.Results The apoptosis rates for the control,model,corilagin,corilagin+pcDNA3.1 and corilagin+pcDNA3.1-TCF7 groups were(5.72±0.49)％,(31.14±5.46)％,(17.01±2.75)％,(16.21±2.83)％and(25.80±3.42)％,respectively;the relative expression levels of Cleaved caspase-9 were 1.00±0.11,3.91±0.41,2.43±0.29,2.49±0.33 and 3.88±0.37,respectively;the relative expression levels for Cleaved caspase-3 were 1.00±0.08,5.04±0.63,3.35±0.48,3.29±0.45 and 4.78±0.56,respectively;the ROS levels were 1.00±0.14,6.27±1.16,2.29±0.32,2.41±0.38 and 5.17±1.08,respectively;malondialdehyde(MDA)levels were(2.33±0.35),(9.26±2.23),(4.80±0.86),(4.47±0.74)and(7.52±1.36)nmol·mg-1,respectively;superoxide dismutase(SOD)levels were(41.34±6.13),(12.15±1.99),(33.38±4.55),(30.01±4.70)and(24.16±3.71)U·mg-1,respectively;and catalase(CAT)levels were(68.22±5.45),(28.27±3.48),(52.13±6.06),(50.24±7.43)and(41.91±5.39)U·mg-1,respectively.When the above indicators in control group compared with those in model group,the above indicators in model group compared with those in the corilagin group,and the above indicators in the corilagin+pcDNA3.1 group compared with those in the corilagin+pcDNA3.1-TCF7 group,all differences showed statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Corilagin can inhibit high-glucose-induced oxidative stress and apoptosis in podocytes,thereby alleviating DN,possibly related to its regulation of the GSK3β/Nrf2 signaling pathway by LncRNA TCF7.