Protective effect of ginkgolide on rats with acute kidney injury and its mechanism

Objective To investigate the protective effect of ginkgolide on acute kidney injury(AKI)rats and its effect on the pathway of AMP activated protein kinase(AMPK)and silent information regulator 1(SIRT1)in kidney tissue. Methods SD rats were randomly divided into control group,AKI model group,low(2.5 mg/kg),medium(5 mg/kg)and high(7.5 mg/kg)dose ginkgolidegroups,with 10 rats in each group.In addition to the control group injected with saline subcutaneously,rats in other groups were injected with gentamicin 80 mg/kg subcutaneously,once a day for 6 days.After establishing the AKI model,rats in the control group and AKI model group were injected intraperitoneally with normal saline,and rats in the ginkgolide groups were injected intraperitoneally with ginkgolide at the corresponding doses,once a day,for a total of 14 days.At one hour after the last administration,the blood and urine of rats in each group were collected,then the rats were killed,and the kidney tissue samples were taken.Enzyme-linked immunosorbent assay was adopted to detect the contents of serum creatinine(Scr),serum urea nitrogen(BUN),serum inflammatory factor interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and neutrophil gelatinase associated lipid transporter(NGAL)and kidney injury factor(KIM-1)in urine;hematoxylin eosin staining(HE)was used to detect the kidney pathological changes in each group;and the contents of superoxide dismutase(SOD)and malondialdehyde(MDA)in kidney tissue were detected withthe kit.Gel electrophoresis mobility shift assay(EMSA)was used to determine the activity of NF-κB in kidney tissue;and Western blot was used to detect the expressions of AMPK/AMPK and SIRT1 in kidney tissue. Results Compared with the Control group,the AKI group showed pathological damages such as disintegration,abscission,vacuolation and degeneration of kidney tubular epithelial cells;the contents of Scr,BUN,NGAL and KIM-1,the contents of TNF-α,IL-6 and MDA in kidney tissues,and the activity of NF-κB in kidney tissue were significantly higher(P<0.05);and the activity of SOD,the protein expressions of pAMPK/AMPK and SIRT1 were significantly lower(P<0.05).Compared with the AKI group,the pathological damage of kidney tubules in the high,middle and low dose ginkgolide groups was alleviated;the contents of Scr,BUN,NGAL,KIM-1,TNF-α,IL-6 and MDA,and the activity of NF-κB in kidney tissue were significantly lower(P<0.05);and the activity of SOD,the protein expressions of pAMPK/AMPK and SIRT1 were significantly higher(P<0.05).Compared with the low dose ginkgolide group,the pathological damage of kidney tubules in the middle and high dose ginkgolide groups was alleviated;the contents of Scr,BUN,NGAL,KIM-1,TNF-α,IL-6 and MDA,and the activity of NF-κB in kidney tissue were significantly lower(P<0.05);and the activity of SOD,the protein expressions of pAMPK/AMPK and SIRT1 were significantly higher(P<0.05). Conclusions By activating AMPK/SIRT1 pathway,ginkgolide may reduce oxidative stress and inflammatory damages of kidney and improve pathological damages of AKI rats.