Soluble epoxide hydrolase inhibitor t-AUCB ameliorates ox-LDL induced conversion of macrophages into foam cells through activating the PPARγ-ABCA1 pathway
10.3760/cma.j.issn.0253-3758.2012.03.014
- VernacularTitle:可溶性环氧化物水解酶抑制剂可抑制小鼠巨噬细胞泡沫化
- Author:
Ting-Ting ZHAO
1
;
Ran PENG
;
Li SHEN
;
Xuan ZHAO
;
Dan-Yan XU
;
Shui-Ping ZHAO
Author Information
1. 中南大学湘雅二医院
- Keywords:
Atherosclerosis;
Macrophages;
Soluble epoxide hydrolase inhibitors
- From:
Chinese Journal of Cardiology
2012;40(3):248-252
- CountryChina
- Language:Chinese
-
Abstract:
Objective To observe the effects of soluble epoxide hydrolase inhibitor t-AUCB on foam cell formation and cholesterol efflux in macrophage.Methods Mouse macrophages RAW264.7 were cultured and stimulated with ox-LDL (80 μmol/L) in the absence (group A) or presence of t-AUCB (1,10,50,100 μmol/L,group B) or t-AUCB (100 μmol/L) pretreated with PPARγ antagonist GW9662 (5 μmol/L,group C).The foam cell was identified by oil red O staining.The cholesterol efflux rates of 3 Hcholesterol in cells were measured by liquid scintillation counter.mRNA and protein expressions of ABCA1 were detected by real-time PCR or Western blot,respectively.Results Oil red O staining showed that t-AUCB (100 μmol/L) significantly inhibited foam cell formation which could be significantly reversed by GW9662 (all P ＜ 0.05).t-AUCB dese-dependently increased cholesterol efflux rates in mouse macrophage [(5.91+0.18)％ in group A,(7.03 ±0.33)％,(8.05 ±0.32)％,( 9.04 ±0.14)％,(10.06±0.85)％ in 1,10,50,100 μmol/L t-AUCB groups,all P＜0.05 vs.group A],which could be reversed by pretreatment with GW9662 [ (6.33 ±0.15)％ in 100 μmol/L t-AUCB + GW9662 group].t-AUCB also upregulated ABCA1 mRNA and protein expressions in a dose-dependent manner which could be significantly attenuated by pretreatment with GW9662.Condusion t-AUCB could inhibit foam cell formation by improving cholesterol efflux through activating PPARγ-ABCA1 pathway in macrophage.
