[Animal modeling] - Study on the mechanism of detoxification and protection of grub peptide extract on lead induced nephrotoxicity in mice

  Objective To study the mechanism of detoxification and protection of grub peptide extract in mice by establishing a lead acetate induced nephrotoxicity model, and to provide experimental basis for the prevention and treatment of lead induced nephropathy.

  Methods The mice were randomly divided into control group, model group, positive drug group and grub peptide groups with different doses (80, 160, 320 mg/kg). All the mice except the control group were intraperitoneally injected lead acetate 20 mg/kg every other day for 15 days. At this time, the mice in the control group and the model group were perfused with normal saline at the same time, while the mice in the positive drug group were perfused with DMSA 70 mg/kg suspension, and the mice in the grub peptide group were perfused with different doses of grub peptide extract, once a day for 15 consecutive days, and the kidney tissue status was observed with HE staining microscope; The indexes of renal function (BUN, Cr), the levels of antioxidant enzymes (SOD, GSH Px) and the contents of peroxides (MDA) in renal tissues were measured; RT-PCR and Western Blot were used to detect and analyze the gene and protein expression levels of phase II detoxification enzyme (NQO1), antioxidant enzyme (HO-1) and signal molecule (Nrf2).

  Results Compared with the model group, the weight of grub peptide group mice increased but was lower than the control group, the morphology of renal tissue was significantly improved, the levels of BUN and Cr in serum were significantly reduced (P<0.05), the levels of antioxidant enzymes (SOD, GSH Px) in renal tissue were significantly increased (P<0.05), the content of MDA was significantly reduced, and the mRNA and protein expression levels of phase II detoxification enzyme gene (NQO1), antioxidant enzyme (HO-1) and signal molecule (Nrf2) were significantly increased (P<0.01).

  Conclusion Grub peptide extract can activate Nrf2-ARE signal pathway, enhance the antioxidant function and enhance the expression of detoxification enzyme gene in lead poisoned mice, thus playing its detoxification and protection role.