Protective effects of grape seed proanthocyanidin extract on rats with diabetic kidney disease from the perspective of SIRT1/PGC-1α pathway
- SONG Yiyun, YU Hui, GAO Zhaoli, LI Xianhua
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Objective To explore the protective effects of grape seed proanthocyanidin extract(GSPE)on rats with diabetic kidney disease(DKD)via silent information regulator 1(SIRT1)/peroxisome proliferator-activator receptor γ coactivator 1α(PGC-1α)signaling pathway. Methods A total of 40 male Sprague Dawley(SD)rats were randomly divided into control, control treatment, model and treatment groups, with 10 rats in each group. The diabetic rat models were induced by intraperitoneal injection of streptozotocin(STZ). Rats in the control treatment and treatment groups received GSPE gavage, while rats in the control and model groups were given equivalent amount of normal saline for 12 weeks. The blood glucose, serum creatinine and urinary microalbumin were detected. The pathological changes of renal tissue were observed with periodic acid Schiff(PAS)staining. Mitochondrial morphology was observed with a transmission electron microscopy. The apoptosis of renal tissue cells was evaluated with Tunel staining. The protein levels of SIRT1/PGC-1α signaling pathway-related molecules of mitochondrial biogenesis, including SIRT1, PGC-1α, nuclear respiratory factor 1(NRF1), and mitochondrial transcription factor A(TFAM)were determined with immunohistochemistry and Western blotting, respectively. Results Compared with the control group, the model group had significantly increased blood glucose ［(39.38±4.18)mmol/L vs(8.21±3.57)mmol/L］, serum creatinine ［(55.83±3.72)μmol/L vs(40.00±2.49)μmol/L］ and urinary microalbumin ［(10.98±3.36)mg/L vs(1.22±0.23)mg/L］(P<0.05). Compared with the control group, the model group had severer histopathological damages and mitochondrial fragmentation in the renal tissue, more significant apoptosis ［(31.81±8.84)% vs(0.50±0.35)%］(P<0.05), but significantly lower expressions of SIRT1(0.34±0.13 vs 0.66±0.06), PGC-1α(0.32±0.03 vs 0.71±0.13), NRF1(0.05±0.01 vs 0.21±0.02), and TFAM(0.06±0.03 vs 0.33±0.06)(P<0.05). Compared with the model group, the treatment group had significantly decreased levels of blood glucose ［(27.26±3.93)mmol/L vs(39.38±4.18)mmol/L］, serum creatinine ［(43.50±1.70)μmol/L vs(55.83±3.72)μmol/L］, urinary microalbumin ［(4.05±2.06)mg/L vs(10.98±3.36)mg/L］ and cell apoptosis ［(4.90±1.62)% vs(31.81±8.84)%］(P<0.05), but significantly increased expressions of SIRT1(0.55±0.05 vs 0.34±0.13), PGC-1α(0.62±0.14 vs 0.32±0.03), NRF1(0.16±0.02 vs 0.05±0.01), and TFAM( 0.26±0.06 vs 0.06±0.03)(P<0.05). Conclusion GSPE may improve mitochondrial biogenesis in DKD rats by regulating SIRT1/PGC-1α signaling pathway, and thus playing a protective role.