The Effect Of PFOS On Atherosclerosis And Its Mechanism

Objective:Epidemiological studies have shown that PFOS is associated with atherosclerosis-related cardiovascular disease,but there is a lack of direct evidence and the mechanism is currently unclear.This study used in vivo and in vitro experiments to observe the effects of PFOS on AS development and explore possible mechanisms.Methods:1.Apo E-/-mice were random Ly divided into two groups,namely the normal chow group and the high-fat chow group.The normal chow group and the high-fat chow group were divided into two subgroups,namely the control group and the PFOS group.In the PFOS group,PFOS solution(5mg/kg · day^-1)was administered orally for 8 weeks.The plasma cholesterol?TC?and triglyceride?TG?content of the mice were measured by biochemical method.Oil red O staining was used to observe the aortic lipid deposition,and the infiltration of macrophages was observed by immunohistochemistry;Western Blot was used to detect the expression of CD36 and Fox O1 in aorta.2.RAW264.7 cells are divided into four groups: control group,PFOS group,ox-LDL group and PFOS and ox-LDL combined action group;MTT method was used to measure the survival rate of RAW264.7 cells,biochemical method was used to detect the intracellular TC content,flow cytometry was used to detect the intracellular ROS level,and chemical method was used to detect the MDA and SOD levels;ELISA method to detect the secretion of inflammatory factors IL-1? ? IL-6 ? TNF-? in the cell supernatant;Fluorescence quantitative PCR was used to detect the quantitative expression levels of IL-1? and TNF-? in cells;Western Blot was used to detect the expression of CD36 and Fox O1 in RAW264.7 cells.Results:1.In the normal chow group,compared with the control group,there was a small amount of lipid deposition and lipid plaque formation in the full length and outflow tract of the aorta in the PFOS group?P<0.05?;In the high-fat chow group,the control group had obvious lipid deposition and lipid plaque formation.Compared with the control group,the lipid deposition and lipid plaque area of the PFOS group increased.In both normal chow and high-fat chow group,the concentration of TC and TG in plasma increased with the administration of PFOS?P<0.05?.In the high-fat chow group,there was obvious brown-yellow CD68 positive expression in the subintimal plaques of the control group,and the area of CD68 positive expression in the PFOS group increased significantly.Compared with the corresponding control group,whether in the normal chow group or the high-fat chow group,the administration of PFOS significantly increased the expression of CD36.In the high-fat chow group,Fox O1 expression increased in the PFOS group compared to the control group;2.PFOS is cytotoxic to RAW264.7 cells.The intracellular TC content increased significantly after ox-LDL treatment,and compared with the ox-LDL group,the increase was more significant in the ox-LDL +PFOS group.Compared with the ox-LDL group,the levels of IL-1?,IL-6,TNF-?,intracellular ROS and the expression of CD36 and Fox O1 in the ox-LDL + PFOS group were significantly increased,while the levels of SOD and MDA were significantly reduced.Conclusions:1.PFOS can promote the formation of atherosclerosis,and its mechanism may be related to increasing blood lipids,promoting lipid deposition,aggravating oxidative stress and inflammatory responses.2.Fox O1 and CD36 may be involved in the foaming effect of PFOS on macrophages.