CAJ | 학술논문

目的：探讨视黄醇X受体（RXR）激动剂贝沙罗汀（Bex）和维生素D受体（VDR）激动剂骨化三醇（Cal）对链脲佐菌素（STZ）诱导的载脂蛋白E基因敲除（ApoE-/-）小鼠胸主动脉硬化及NF-κB表达的影响。方法：动物分6组：C57组、ApoE-/-组、STZ-ApoE-/-组、STZ-ApoE-/-＋Bex（10 mg· kg-1· d-1）组、STZ-ApoE-/-＋Cal（10μg/kg）组和STZ-ApoE-/-＋Bex＋Cal组。 STZ腹腔注射复制糖尿病动物模型，Western blotting 法及免疫组化法测定小鼠胸主动脉中NF-κB的表达， HE染色观察小鼠胸主动脉斑块的面积。结果：与C57组相比，ApoE-/-组的血糖水平无明显差别，血清总胆固醇（ TC）及低密度脂蛋白（ LDL）水平升高（ P＜0.05）；STZ-ApoE-/-组的血糖及血清TC和LDL水平较ApoE-/-组明显增高（P＜0.05），Bex和Cal对小鼠的血糖及血清TC、LDL无影响。与C57组相比，ApoE-/-和STZ-ApoE-/-小鼠胸主动脉的NF-κB蛋白表达显著增加；与STZ-ApoE-/-组相比，Bex和Cal均显著降低NF-κB的水平（P＜0．05），联合用药降低更明显（P＜0.01）。与STZ-ApoE-/-组相比，Bex和Cal可缩小STZ-ApoE-/-小鼠的胸主动脉斑块面积（均P＜0.05）；与Bex组相比，联合组斑块面积缩小的程度有显著差异（ P＜0.05）。结论：Bex和Cal可降低STZ-ApoE-/-小鼠胸主动脉粥样硬化斑块面积及NF-κB的表达，联合有协同作用，由此推论Bex和Cal的抗动脉粥样硬化机制可能与其对NF-κB的调节有关。
목적：탐토시황순X수체（RXR）격동제패사라정（Bex）화유생소D수체（VDR）격동제골화삼순（Cal）대련뇨좌균소（STZ）유도적재지단백E기인고제（ApoE-/-）소서흉주동맥경화급NF-κB표체적영향。방법：동물분6조：C57조、ApoE-/-조、STZ-ApoE-/-조、STZ-ApoE-/-＋Bex（10 mg· kg-1· d-1）조、STZ-ApoE-/-＋Cal（10μg/kg）조화STZ-ApoE-/-＋Bex＋Cal조。 STZ복강주사복제당뇨병동물모형，Western blotting 법급면역조화법측정소서흉주동맥중NF-κB적표체， HE염색관찰소서흉주동맥반괴적면적。결과：여C57조상비，ApoE-/-조적혈당수평무명현차별，혈청총담고순（ TC）급저밀도지단백（ LDL）수평승고（ P＜0.05）；STZ-ApoE-/-조적혈당급혈청TC화LDL수평교ApoE-/-조명현증고（P＜0.05），Bex화Cal대소서적혈당급혈청TC、LDL무영향。여C57조상비，ApoE-/-화STZ-ApoE-/-소서흉주동맥적NF-κB단백표체현저증가；여STZ-ApoE-/-조상비，Bex화Cal균현저강저NF-κB적수평（P＜0．05），연합용약강저경명현（P＜0.01）。여STZ-ApoE-/-조상비，Bex화Cal가축소STZ-ApoE-/-소서적흉주동맥반괴면적（균P＜0.05）；여Bex조상비，연합조반괴면적축소적정도유현저차이（ P＜0.05）。결론：Bex화Cal가강저STZ-ApoE-/-소서흉주동맥죽양경화반괴면적급NF-κB적표체，연합유협동작용，유차추론Bex화Cal적항동맥죽양경화궤제가능여기대NF-κB적조절유관。
[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.