Effects and related mechanism of retinoid X receptor agonist bexarotene on atherosclerosis progression in diabetic apoE-/-mice
10.3760/cma.j.issn.0253-3758.2014.06.013
- VernacularTitle:视黄醇X受体激动剂蓓萨罗丁抑制糖尿病载脂蛋白E-/-小鼠动脉粥样硬化的形成及其机制
- Author:
Jiang ZHU
1
;
Changsheng XU
;
Ruobing NING
;
Dajun CHAI
;
Jinxiu LIN
Author Information
1. 福建医科大学附属第一医院心血管内科
- Keywords:
Diabetes mellitus;
Atherosclerosis;
Oxidative stress;
Retinoid X receptor
- From:
Chinese Journal of Cardiology
2014;42(6):492-497
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of retinoid X receptor (RXR) agonist bexarotene on atherosclerosis and the potential mechanism in streptozotocin (STZ) induced diabetic apolipoprotein E knockout (apoE-/-) mice.Methods Eight C57BL/6 mice served as control,46 apoE-/-mice were randomized into 4 groups:apoE-/-group (n =10),STZ + apoE-/-group (n =12),STZ + apoE-/-+ Bex 10 (10 mg · kg-1 · d-1)group (n=12),STZ+ apoE-/-+Bex 30 (30 mg · kg-1 · d-1)group (n=12).Diabetic apoE-/-animal model was established by intraperitoneal injection of STZ.Blood glucose was determined by glucose oxidase method.Patch area in thoracic aorta was measured by HE staining.Western blotting was used to determine the RXR and gp91 phox protein level in thoracic aorta.Reactive oxygen species (ROS) level in blood and thoracic aorta homogenates was detected by Fenton and Griess method.Results (1) Patch areas of thoracic aorta were larger in apoE-/-group than in C57BL/6 group[(38.40 ± 8.95) μm2 vs.(0.10 ±0.01) μm2,P ＜0.01],further increased in STZ + apoE-/-group [(94.06 ± 8.04) μm2,P ＜0.05 vs.apoE-/-group] and significantly reduced in STZ + apoE-/-+ Bex 10 group [(78.72 ± 4.62)μm2,P ＜0.05 vs.STZ + apoE-/-group] and further educed in STZ + apoE-/-+ Bex 30 group[(46.13 ±7.56) μm2,P ＜ 0.05 vs.STZ + apoE-/-+ Bex 10 group].(2) Blood glucose level,TG,TC,LDL-C,thoracic aorta gp91 phox protein level and ROS level in blood and thoracic aorta homogenates were significantly higher in STZ + apoE-/-group than in apoE-/-group (all P ＜ 0.05).Blood glucose level and TG,TC,LDL-C levels were similar between STZ + apoE-/-+ Bex10 and STZ + apoE-/-group.Thoracic aorta gp91 phox protein level and ROS level in blood and thoracic aorta homogenates were lower in STZ + apoE-/-+ Bex 10 group than in STZ + apoE-/-group (P ＜ 0.05).Blood glucose level,TG,TC,LDL-C levels,gp91 phox expression in thoracic aorta,ROS level in blood and thoracic in STZ + apoE-/-+ Bex 30 group were lower than in STZ + apoE-/-group (all P ＜ 0.05).Conclusion Bexarotene treatment could attenuate arteriosclerosis progression in STZ induced diabetic apoE-/-mice,the underlying mechanism might be related to suppressing oxidative stress and decreasing blood glucose level and improving lipids metabolism.
