Intrevenous Vitamin C Attenuates Hemorrhagic Shock Related Renal Injury Through The Induction Of SIRT1 In Rats

Objective: To investigate the effect of intravenous Vitamin C(VC)on hemorrhagic shock(HS)-associated rat renal injury and the involved mechanism.Methods: Thirty SD rats were randomly assigned to the sham surgery(sham),hemorrhagic shock(HS),HS+100 mg/kg VC(H+VL),HS+500 mg/kg VC(H+VH)and HS+100 mg/kg VC+EX527(H+VL+E)groups.Tissue and blood samples were collected 6 h after surgery.Kidney pathological changes were scored.Creatinine(CRE),blood urea nitrogen(BUN),tumor necrosis factor-α(TNF-α),and interleukin-1β(IL-1β)levels in serum and Vitamin C levels and superoxide dismutase(SOD)activity and the ability to suppress hydroxyl radical(RAFHR)in plasma were measured.The expression of Sirtuin1(SIRT1),Acetyl-NF-k B(Ace-NF-k B),heme oxygenase-1(HO-1),TNF-α,and IL-1β in tissues was analyzed by ELISA and western-blot.Results: In the HS group,the kidney pathological score and CRE,BUN,TNF-α,and IL-1β levels in serum were significantly higher than in the Sham group(P<0.05),while SOD and RAFHR were significantly decreased in the plasma(P<0.05).SOD activity and SIRT1 expression were remarkably lower in the kidney in the HS group than in the Sham group(P<0.05),while MDA,TNF-α,and IL-1β concentrations and Acetyl-NF-k B and HO-1 expression in the kidney showed a noteworthy increase compared to the Sham group(P<0.05).Compared to the HS group,VC treatment led to a remarkable reduction in the kidney pathological score and CRE,BUN,TNF-α,and IL-1β levels(P<0.05),and a significant increase in Vitamin C,SOD,and RAFHR levels in the plasma(P<0.05).Additionally,MDA,TNF-α,IL-1β and Acetyl-NF-k B expression levels were decreased in the kidney(P<0.05),while SOD,SIRT1 and HO-1levels were notably enhanced.There were no differences between the H+VL and H+VH groups aside from plasma Vitamin C levels.The effect of Vitamin C was decreased after the addition of EX527,which inhibits SIRT1.Conclusions: Intravenous Vitamin C might attenuate HS-related renal injury via the SIRT1 pathway,and it appears that there were no differences in the effects between the high and low doses.