Mechanism Of Nrf2 In Folic Acid-induced Acute Renal Injury

Objective:AKI is a common clinical syndrome.Nrf2 is a regulatory factor in maintaining cells at oxidative stress level.Through its mediated antioxidant response system,normal cells resist exogenous and endogenous oxidative stress,which enhances the antioxidant function of the cells.It is generally believed that oxidative stress leads to the occurrence of AKI.It has been proved that Nrf2 has protective effect on renal injury.So this study is about the role and the mechanism of Nrf2 in folic acid-induced AKI.Methods:In this study,Nrf2 knockout mice and C57BL/6 mice were studied.The experimental group was given 100 mg/kg folic acid intravenously,and the control group was injected with the same dose of NaHCO3.After 2 days injection,we collected the serum and kidney tissues.We detected the serum BUN,Scr,Gclm,IL 6,Tnfα,caspase1,pycard and Txnip-1/2 ect.Result.After 48 hours of folic acid injection1.The renal volume of both Nrf2^+/+mice and Nrf2^-/-mice were increased,serum urea nitrogen and serum creatinine levels were significantly higher than those in the control group.2.HE and PAS staining of renal pathological injury showed that acute renal injury occurred in Nrf2^+/+mice and Nrf2^-/-mice,the pathological damage was more serious in Nrf2^-/-mice.3.The expression of NQO1,GCLC and GCLM mRNA in FA group was down regulated.It suggests that the deletion of Nrf2 after folic acid injection inhibited the oxidative stress response.4.There was significant difference in the increase of mRNA levels between il-6 and TNF-αin Nrf2^-/-mice.5.Tunel staining showed that the apoptosis of Nrf2^-/-mice was significantly higher than that of Nrf2^+/+mice.6.The level of gpx4 mRNA levels in folic acid group was significantly lower than that in Nrf2^+/+mice.7.The expression of Mthfd mRNA levels in folic acid group increased significantly,but there was no difference between Nrf2^+/+and Nrf2^-/-group.Conclusion:1.Nrf2 has protective effect on acute renal injury induced by folic acid.2.The mechanism of Nrf2 in acute renal injury induced by folic acid may be:Nrf2 inhibits inflammatory factor,Nrf2 inhibits oxidative stress,Nrf2 inhibition apoptosis,Nrf2inhibition ferroptosis.