中国病理生理杂志Issue(8)：1472-1477,6.DOI:10.3969/j.issn.1000-4718.2014.08.023
RXR／VDR 激动剂对糖尿病 ApoE -／-小鼠胸主动脉硬化及 NF-κB 表达的调控
Regulatory effect of RXR/VDR agonists on atherosclerosis and NF-κB ex-pression in diabetic ApoE knockout mice
摘要
Abstract
[ABSTRACT]AIM:ToexploretheeffectofretinoidXreceptor(RXR)agonistbexarotene(Bex)andvitaminD receptor (VDR) agonist calcitriol (Cal) on the expression of nuclear factor-kappa B (NF-κB) and the development of atherosclerosis in streptozotocin-induced diabetic apolipoprotein E knockout ( STZ-ApoE-/-) mice.METHODS: Male mice were treated for 12 weeks as follows:(1) C57+vehicle;(2) ApoE-/-+vehicle;(3) STZ-ApoE-/-+vehicle;(4) STZ-ApoE-/-+Bex (10 mg· kg-1· d-1);(5) STZ-ApoE-/-+Cal (10 μg/kg, twice a week);(6) STZ-ApoE-/-+Bex (10 mg· kg-1· d-1) +Cal (10 μg/kg, twice a week).Intraperitoneal injection of STZ was performed to establish the diabetic animal model .Western blotting and immunohistochemical method was used to detect NF-κB level in the thorac-ic aorta.Plaque area in the thoracic aorta was measured using HE staining .RESULTS:Compared with the C57 mice, the fasting blood glucose in the ApoE-/-mice was not remarkably changed .The levels of total cholesterol ( TC) and low-densi-ty lipoprotein ( LDL) were greatly increased .The fasting blood glucose and lipid levels in STZ-ApoE-/-group were much higher than those in ApoE-/-group.Compared with STZ-ApoE-/-group, the fasting blood glucose and lipid levels in Bex group and Cal group were not significantly changed .Compared with the C57 mice, the protein expression of NF-κB in the ApoE-/-mice and the STZ-ApoE-/-mice was remarkably increased .Compared with STZ-ApoE-/-group, the levels of NF-κB in Bex group, Cal group and combination group were greatly decreased .Compared with STZ-ApoE-/-group, the thoracic artery plaque areas in Bex group and Cal group were inhibited (both P<0.05).Compared with Bex group, the plaque area of the thoracic artery in combination group was significantly decreased (P<0.05).CONCLUSION:Bexaro-tene or calcitriol decreases the development of atherosclerosis in streptozotocin -induced diabetic ApoE-/-mice.Bexarotene combined with calcitriol affords greater protection than monotherapy .The mechanism may be involved in down-regulating the expression of NF-κB.关键词
动脉粥样硬化/糖尿病/贝沙罗汀/骨化三醇/NF-κBKey words
Atherosclerosis/Diabete smellitus/Bexarotene/Calcitriol/NF-kappa B分类
医药卫生引用本文复制引用
刘永萍,彭峰,许昌声,柴大军,林金秀..RXR／VDR 激动剂对糖尿病 ApoE -／-小鼠胸主动脉硬化及 NF-κB 表达的调控[J].中国病理生理杂志,2014,(8):1472-1477,6.基金项目
国家自然科学基金青年基金资助项目 （）
