An Effect On Cholesterol Content In Foam Cells By Interfering The Erk1 /2 And Nf-κb Signal Pathway With Ang-(1-7)

Objective To Invstigate the regulation of Ang-(1-7) to the expression of the activity of ERK1/2and the activity of NF-κB in THP-1 derived-foam cells and to analyize the relationship betweenthe ERK1 /2 signal pathway and the NF-κB signal pathway. Methods To establish amacrophage-derived foam cell model of human monocylic THP-1 cell line，Handle the cells indifferent conditions for 72 hours，medium added nothing,Foam cell group, Advance by(10-6mol/lAng-(1-7), 10μmol/lPD98059,10μmol/lTPCK,10-6mol/lAng-(1-7) +10μmol/lTPCK,10-6mol/l Ang-(1-7) +10μmol/l PD98059) intervention foam cells group.the differentiated cellswere observed after oil red O staining under light microscope，High performance liquidchromatography/atmospheric pressure chemical ionization tandem massspectrometry(HPLC-MS) was used for quantitative analysis of cellular cholesterol ,Immunohistochemistry was employed to identify the expression of NF-κB in thedifferentiated cells, Detection of the expression of p- ERK1/2 and ABCA1 protection in thedifferentiated cells by Western Blot.Results Ang(1-7) downregulated the expression of theactivity of ERK1/2 and the activity of NF-κB in(P< 0.05), enhanced the ABCA1 proteinsproduction(P< 0.05),Meanwhile,Ang(1-7) downregulated the content of cholesterol in THP-1derived foam cells (P< 0.05), Specific inhibitor PD098059 and specific inhibitor TPCK was usedto reduce the content of total cholesterol in THP-1 derived foam cells (P< 0.05), Compared withpovidone Ang-(1-7) and specific inhibitor PD098059 or specific inhibitor TPCK was proved tobe significantly decrease the content of total cholesterol in THP-1 derived foam cells (P< 0.01);Specific inhibitor TPCK was used to abrogate phosphorylation of NF-κB for further evaluation（P＜0.01）,but didn’t abrogate phosphorylationof ERK1/ 2 for further evaluation（P＞0.05）,Specific inhibitor PD98059 was used to abrogate phosphorylation of ERK1/2 and NF-κB forfurther evaluation（P＜0.05）. Conclusion Ang (1-7) can increase the expression of ABCA1protein and lessen the content of cholesterol in THP-1 derived foam cells by decreasing theactivity of ERK1/2 and the activity of NF-κB；Specific inhibitor PD098059 and specific inhibitorTPCK was used to reduce the content of total cholesterol in THP-1 derived foam cells；ERK1/2may be the upstream substance before NF-κB inthe signaling pathway.