CAJ | 학술논문

目的观察高脂饮食后载脂蛋白E( ApoE)和低密度脂蛋白受体(LDLR)基因敲除(ApoE-/-和LDLR-/-)小鼠动脉粥样硬化(AS)斑块内的组织病理学特征、核因子-κB(NFκB)及其抑制蛋白(IKB)的表达以及钙沉积变化,研究高脂饮食对ApoE-/-和LDLR-/-小鼠血管的影响及其作用机制.方法 8只C57BL/6J小鼠为普食对照组,ApoE -/-和LDLR-/-小鼠分成普食和高脂饮食各两组,每组8只,连续喂养4个月.取各组小鼠主动脉进行苏木素-伊红染色、油红O染色和钙沉积检测,用免疫组织化学法观察AS斑块内NFκB和IKB的表达水平,荧光双标法分析AS斑块内NFκB的表达与巨噬细胞和平滑肌细胞的相关关系.结果 ApoE-/-和LDLR-/-小鼠各高脂饮食组AS斑块均大于普食组,脂肪沉积多于普食组,NFκB和IKB的表达水平均显著高于普食组(P均＜0.05).NFκB主要表达于平滑肌细胞.ApoE-/-小鼠高脂饮食组钙沉积反应明显大于其普食组(P＜0.05),但LDLR-/-小鼠高脂饮食组钙沉积反应与其普食组比较,差异无统计学意义(P＞0.05).结论高脂饮食促进ApoE-/-和LDLR-/-小鼠AS斑块的形成,上调NFκB和IKB的表达水平,增加钙沉积反应,从而加剧了血管壁损伤.
목적 관찰고지음식후재지단백E( ApoE)화저밀도지단백수체(LDLR)기인고제(ApoE-/-화LDLR-/-)소서동맥죽양경화(AS)반괴내적조직병이학특정、핵인자-κB(NFκB)급기억제단백(IKB)적표체이급개침적변화,연구고지음식대ApoE-/-화LDLR-/-소서혈관적영향급기작용궤제.방법 8지C57BL/6J소서위보식대조조,ApoE -/-화LDLR-/-소서분성보식화고지음식각량조,매조8지,련속위양4개월.취각조소서주동맥진행소목소-이홍염색、유홍O염색화개침적검측,용면역조직화학법관찰AS반괴내NFκB화IKB적표체수평,형광쌍표법분석AS반괴내NFκB적표체여거서세포화평활기세포적상관관계.결과 ApoE-/-화LDLR-/-소서각고지음식조AS반괴균대우보식조,지방침적다우보식조,NFκB화IKB적표체수평균현저고우보식조(P균＜0.05).NFκB주요표체우평활기세포.ApoE-/-소서고지음식조개침적반응명현대우기보식조(P＜0.05),단LDLR-/-소서고지음식조개침적반응여기보식조비교,차이무통계학의의(P＞0.05).결론 고지음식촉진ApoE-/-화LDLR-/-소서AS반괴적형성,상조NFκB화IKB적표체수평,증가개침적반응,종이가극료혈관벽손상.
Objective To observe the histopathological features,nuclear factor-κB (NFκB) and IKB expressions as well as calcium deposition of atherosclerosis plaques (AS) in apolipoprotein E (ApoE) and low density lipoprotein receptor (LDLR) knockout mice (ApoE-/-, LDLR-/- fed high-fat diet.Methods Eight C57BL/6J mice fed with normal diet were used as control,32 ApoE-/- mice and LDLR -/- mice were divided into normal diet and high-fat diet groups ( n =8 each).After 4 months,aorta was collected for morphologic ( HE,Oil Red O,Von Kossa ) and immunohistochemistry ( nuclear factor-κB,IKB,macrophage surface molecule-3, α-smooth activor protein ) analysis.Results Degree of AS in ApoE -/ - and LDLR-/- mice fed with high-fat diet were significantly severer than those fed with normal diet and AS was more significant in ApoE-/- mice than in LDLR -/- mice.NFκB and IKB expressions in high-fat diet group were significantly higher than the normal diet group ( P ＜ 0.05 ). Double-labeling of NFκB revealed dominant expression in smooth muscle cells.Calcium deposition was significantly more in ApoE-/- mice fed with high-fat diet than mice fed with normal diet (P ＜0.05) and was similar in LDLR-/- mice fed with high and normal diet (P ＞ 0.05 ).Conclusion High-fat diet contributes to the formation of AS plagues in ApoE -/- and LDLR -/- mice joined by upregulated NFκB and IKB expressions and calcium deposition.