The Regulating Effect Of Puerarin On Thioredoxin-1 Expression And Inhibits Macrophage Uptake Of OxLDL

Objective: Puerarin has anti-inflammatory and antioxidant effects and can prevent and treat cardiovascular diseases.Thioredoxin(Trx)can regulate the oxidative stress of cells and improve the functional status of cells by removing reactive oxygen species(ROS),which has been shown to have an important role in the treatment of atherosclerosis.The study mainly analyzed the role of puerarin in regulating Trx1 activity and the uptake of oxidized low-density lipoprotein(oxLDL)by macrophages,and explored its molecular mechanism.Methods: 1.In vitro culture of mouse-derived macrophages(RAW264.7),induced with 50?g / m L oxLDL or 25 ?g / m L Dil-oxLDL and treated with different concentrations(10 ?M,50 ?M)of puerarin.Flow cytometry was used to detect ROS content and lipid absorption,and Western blot was used to detect related protein expression.Cells were co-treated with Trx1 inhibitor PX-12 and puerarin to detect lipid absorption and ROS,and Western blot was used to detect the expression of related proteins.2.Eight-week-old male apo E-/-mice were randomly divided into four groups and treated as follows: normal diet group(ND),high-fat model group(HFD),puerarin group(100 mg/kg)and PX-12 In the group(puerarin 100mg/kg+PX-12),after treatment,the peritoneal macrophages of the mice were taken and Western blot was used to detect the expression of Trx-1,scavenger receptor and related proteins.Results: 1.Puerarin upregulates the expression of Trx1 in macrophages RAW264.7,and affects the expression of Trx1 related proteins thioredoxin reductase(Trx R)and thioredoxin interaction protein(Txnip),and regulates ROS in macrophages.Puerarin inhibits the expression of scavenger receptors SR-A,LOX-1 and CD36 related to oxLDL uptake,thereby inhibiting the formation of foam cells.The PX-12 inhibitor inhibited the expression of Trx1,which counteracted the down-regulation of SR-A and LOX-1 expression by puerarin,indicating that the inhibition of oxLDL by puerarin is directly related to the regulation of Trx1 expression.The up-regulation of Nrf2 expression by puerarin is positively correlated with the regulation of Trx1 expression.2.In vivo experiments showed that puerarin inhibited the expression of scavenger receptors SR-A and LOX-1 in peritoneal macrophages,upregulated the expression of Trx1 and Trx R,and this effect was inhibited after the addition of inhibitor PX-12.Conclusion: 1.Puerarin controls ROS in macrophages by regulating the expression of Trx.2.Puerarin inhibits the uptake of oxLDL by macrophages and down-regulates the expression of CD36,SR-A and LOX-1.3.Puerarin inhibits the uptake of oxLDL by macrophages and increases the expression of Trx1.4.In macrophages,puerarin may regulate Trx1 through Nrf2.