Effects Of Different Concentrations Of Selenium On Nrf2-ARE Signaling Pathway In Kidney Injury Induced By Fluoride In Rats

[Objective] The purpose of this study was to investigate the mechanism of fluorosis on animal kidney and the effect of different concentrations of selenium in Nrf2-ARE signaling pathway to alleviate fluorosis.[Methods] Fifty male SD rats were randomly divided into control group(C,distilled water),high fluoride group(F,100 mg/L Na F water),group I(0.5 mg/L Na2 Se O3,100 mg/L Na F water),group II(1mg/L Na2 Se O3,100 mg/L Na F water),group III(2 mg/L Na2 Se O3,100 mg/L Na F water),after 10 weeks,serum and kidney tissues were collected and Ca2+,Scr,BUN,MDA,CAT,GSH-Px and ROS were measured.The gene and protein expression of Mst1/2,Nrf2,Keap1,HO-1,NQO1,MEK5,ERK5,AMPK,e NOS,PI3 K,Calpain2 were detected.[Results] 1.Compared with group C,the levels of Scr,MDA and ROS in group F obviously increased(p < 0.05,p < 0.01),the levels of CAT in group F decreased significantly(p < 0.001).Compared with group F,the levels of CAT in group I decreased significantly(p < 0.01),the levels of MDA and ROS decreased significantly(p < 0.01,p < 0.001),and the increase of GSH-Px was significant(p < 0.05)in group II,the decrease of SCR and MDA in group III were significant(p < 0.05).2.Compared with group C,the results of HE staining showed edema,necrosis and vacuolation of renal cells in group F.Compared with group F,it was significantly improved in group Ⅱ and Ⅲ.The results of IHC staining showed that the positive staining of HO-1 and NQO1 protein were the strongest in group F compared with group C,and the positive staining of Nrf2 protein was the strongest in group F,which was widely distributed in cytoplasm and nucleus,and it was alleviated to some extent in group Ⅰ,Ⅱ and Ⅲ.3.Compared with group C,fluoride intake significantly increased the expression of HO-1 and Mst2protein(p < 0.05,p < 0.01)and notably decreased the expression of Nrf2 protein(p < 0.001).After treatment with different doses of selenium,the protein expression of HO-1,Nrf2 and NQO1 in group Ⅰincreased evidently(p < 0.05,p < 0.01),while the expression of Mst2 protein decreased remarkably(p <0.001).In group Ⅱ,the expression of NQO1 and HO-1 increased significantly(p < 0.05,p < 0.01),while the expression of Mst2,Mst1 and Calpain2 decreased significantly(p < 0.05,p < 0.01).In group Ⅲ,the expression of HO-1,Nrf2 and NQO1 increased significantly(p < 0.05,p < 0.01),and the expression of Mst1,Mst2 and Calpain2 decreased significantly(p < 0.05,p < 0.01).4.Compared with group C,the expression of m RNA of HO-1,NQO1,and Nrf2 in group F increased significantly(p < 0.05,p < 0.01),while the expression of m RNA of Keap1,e NOS,MEK5,and ERK5 decreased remarkably(p < 0.05,p < 0.01).Compared with group F,the expression of Nrf2,HO-1,and NQO1 m RNA were significantly decreased in group Ⅰ(p < 0.05,p < 0.01).The expression of Nrf2,HO-1and NQO1 m RNA decreased significantly in group Ⅱ(p < 0.05,p < 0.01).The expression of Nrf2,HO-1,and NQO1 m RNA decreased significantly in group Ⅲ(p < 0.05,p < 0.01).[Conclusion] 100 mg/L Na F can obviously damage the kidney of rats,selenium supplement in the diet can alleviate the damage of kidney by Nrf2-ARE signal pathway,among which 1 mg/L selenium supplement has a better effect.