敲降MALAT1减轻ox-LDL诱导的巨噬细胞炎性反应和细胞损伤OA

Objective To explore the role and potential mechanism of metastasis-associated lung adenocarcinoma transcript 1(MALAT1)in inflammatory response and cell damage of macrophages induced by oxidized low density lipoprotein(ox-LDL).Methods THP-1 cells were induced to differentiate into macrophages by phorbol ester(PMA).Macrophages were co-cultured with ox-LDL to construct a cell injury model.Lipid accumulation was ob-served by Oil Red O staining microscopy.MALAT1 was knocked down by transfection of shRNA.The experimental group included control group,ox-LDL group,ox-LDL+shNC group and ox-LDL+shMALAT1 group.Total cholesterol and triglyceride in cells were measured.Apoptosis was detected by flow cytometry.The level of IL-6,TNFα and MCP-1 were detected by ELISA.The expression of NLRP3,RIPK1,caspase-8,p65 and SR-A was detected by RT-qPCR and Western blot.Results Compared with the control group,the cell lipid accumulation,total cholesterol and triglyceride contents,cell apoptosis,IL-6,TNFα and MCP-1 levels and the expression of NLRP3,RIPK1,caspase-8,p-p65 and SR-A increased significantly in ox-LDL group(P＜0.05).Compared with ox-LDL group,ox-LDL+shMALAT1 group the contents of total cholesterol and triglyceride,apoptosis,IL-6,TNFα and MCP-1,and the expression of NLRP3,RIPK1,caspase-8,p-p65 and SR-A all significantly decreased(P＜0.05).Conclusions MALAT1 may play an important role in ox-LDL-induced cell injury by regulating NLRP3 inflammatory corpuscles and related signal pathways.Knockdown of MALAT1 can significantly reduce the inflammatory reaction and cell damage in-duced by ox-LDL,which provides a potential target for the treatment of atherosclerosis.