中华病理学杂志
中華病理學雜誌
중화병이학잡지
Chinese Journal of Pathology
2011年
6期
397-402
,共6页
动脉粥样硬化%一氧化碳%血红素氧化酶(脱环)%模型,动物
動脈粥樣硬化%一氧化碳%血紅素氧化酶(脫環)%模型,動物
동맥죽양경화%일양화탄%혈홍소양화매(탈배)%모형,동물
Atherosclerosis%Carbon monoxide%Heme oxygenase(Decyclizing)%Models,animal
目的 探讨血红素氧合酶1(HO-1)/一氧化碳(CO)系统对动脉粥样硬化斑块形成的影响及其机制.方法 新西兰大白兔32只,分为4组;对照组、胆固醇组、血红素组及卟啉锌组,每组8只.其中对照组喂饲普通饲料,胆固醇组喂饲含1.5%胆固醇饲料,血红素组及卟啉锌组在予以高胆固醇饮食的同时,分别经腹腔注射氯化血红素(HO激动剂,15 mg·kg-1·d-1)或锌原卟啉9(HO抑制剂,45 μmol·kg-1·d-1),共12周,12周末处死动物,取出胸、腹主动脉行病理形态学观察和HO-1、内皮素1(ET-1)免疫组织化学及Western blot分析.结果 主动脉大体油红O染色示对照组无斑块形成,胆固醇组斑块所占面积比为(54.0±4.2)%,与胆固醇组比较,卟啉锌组斑块所占面积比[(61.1±3.5)%]显著增大(P<0.01),而血红素组斑块所占面积比[(17.9±3.0)%]显著减小(P<0.01).透射电镜示胆固醇组内皮消失,代之以粥样物质,弹力层及平滑肌层结构紊乱,平滑肌细胞胞质内充满脂质空泡,胶原纤维增生;卟啉锌组上述改变加重,血红素组浅层平滑肌结构略微不整齐,余无明显异常.HE染色示胆固醇组内膜增厚[(74.6±39.0)μm],内皮细胞脱落,泡沫细胞增生明显,中膜萎缩、变薄、平滑肌结构和排列紊乱;卟啉锌组上述改变加重,内膜增厚更显著[(127.2±49.8)μm,P<0.01];血红素组内膜厚度[(48.5±42.3)μm]较胆固醇组显著减少(P<0.01),内皮细胞无脱落,少许泡沫细胞增生,平滑肌结构和排列正常.与对照组比较,胆固醇组主动脉cNOS活性、NO生成量明显降低,HO-1表达、CO生成量明显增高(均P<0.01);与胆固醇组比较,氯化血红素干预显著增高HO-1表达、CO生成量,而显著降低ET-1表达(均P<0.01),锌原卟啉9显著降低HO-1表达、CO生成量,而显著增高ET-1表达(均P<0.01).结论 HO-1/CO系统具有预防动脉粥样硬化斑块形成的作用,其机制可能与该系统代偿和调节NOS/NO系统以及下调ET-1表达从而改善血管内皮功能、抑制平滑肌细胞增殖有关.
目的 探討血紅素氧閤酶1(HO-1)/一氧化碳(CO)繫統對動脈粥樣硬化斑塊形成的影響及其機製.方法 新西蘭大白兔32隻,分為4組;對照組、膽固醇組、血紅素組及卟啉鋅組,每組8隻.其中對照組餵飼普通飼料,膽固醇組餵飼含1.5%膽固醇飼料,血紅素組及卟啉鋅組在予以高膽固醇飲食的同時,分彆經腹腔註射氯化血紅素(HO激動劑,15 mg·kg-1·d-1)或鋅原卟啉9(HO抑製劑,45 μmol·kg-1·d-1),共12週,12週末處死動物,取齣胸、腹主動脈行病理形態學觀察和HO-1、內皮素1(ET-1)免疫組織化學及Western blot分析.結果 主動脈大體油紅O染色示對照組無斑塊形成,膽固醇組斑塊所佔麵積比為(54.0±4.2)%,與膽固醇組比較,卟啉鋅組斑塊所佔麵積比[(61.1±3.5)%]顯著增大(P<0.01),而血紅素組斑塊所佔麵積比[(17.9±3.0)%]顯著減小(P<0.01).透射電鏡示膽固醇組內皮消失,代之以粥樣物質,彈力層及平滑肌層結構紊亂,平滑肌細胞胞質內充滿脂質空泡,膠原纖維增生;卟啉鋅組上述改變加重,血紅素組淺層平滑肌結構略微不整齊,餘無明顯異常.HE染色示膽固醇組內膜增厚[(74.6±39.0)μm],內皮細胞脫落,泡沫細胞增生明顯,中膜萎縮、變薄、平滑肌結構和排列紊亂;卟啉鋅組上述改變加重,內膜增厚更顯著[(127.2±49.8)μm,P<0.01];血紅素組內膜厚度[(48.5±42.3)μm]較膽固醇組顯著減少(P<0.01),內皮細胞無脫落,少許泡沫細胞增生,平滑肌結構和排列正常.與對照組比較,膽固醇組主動脈cNOS活性、NO生成量明顯降低,HO-1錶達、CO生成量明顯增高(均P<0.01);與膽固醇組比較,氯化血紅素榦預顯著增高HO-1錶達、CO生成量,而顯著降低ET-1錶達(均P<0.01),鋅原卟啉9顯著降低HO-1錶達、CO生成量,而顯著增高ET-1錶達(均P<0.01).結論 HO-1/CO繫統具有預防動脈粥樣硬化斑塊形成的作用,其機製可能與該繫統代償和調節NOS/NO繫統以及下調ET-1錶達從而改善血管內皮功能、抑製平滑肌細胞增殖有關.
목적 탐토혈홍소양합매1(HO-1)/일양화탄(CO)계통대동맥죽양경화반괴형성적영향급기궤제.방법 신서란대백토32지,분위4조;대조조、담고순조、혈홍소조급계람자조,매조8지.기중대조조위사보통사료,담고순조위사함1.5%담고순사료,혈홍소조급계람자조재여이고담고순음식적동시,분별경복강주사록화혈홍소(HO격동제,15 mg·kg-1·d-1)혹자원계람9(HO억제제,45 μmol·kg-1·d-1),공12주,12주말처사동물,취출흉、복주동맥행병리형태학관찰화HO-1、내피소1(ET-1)면역조직화학급Western blot분석.결과 주동맥대체유홍O염색시대조조무반괴형성,담고순조반괴소점면적비위(54.0±4.2)%,여담고순조비교,계람자조반괴소점면적비[(61.1±3.5)%]현저증대(P<0.01),이혈홍소조반괴소점면적비[(17.9±3.0)%]현저감소(P<0.01).투사전경시담고순조내피소실,대지이죽양물질,탄력층급평활기층결구문란,평활기세포포질내충만지질공포,효원섬유증생;계람자조상술개변가중,혈홍소조천층평활기결구략미불정제,여무명현이상.HE염색시담고순조내막증후[(74.6±39.0)μm],내피세포탈락,포말세포증생명현,중막위축、변박、평활기결구화배렬문란;계람자조상술개변가중,내막증후경현저[(127.2±49.8)μm,P<0.01];혈홍소조내막후도[(48.5±42.3)μm]교담고순조현저감소(P<0.01),내피세포무탈락,소허포말세포증생,평활기결구화배렬정상.여대조조비교,담고순조주동맥cNOS활성、NO생성량명현강저,HO-1표체、CO생성량명현증고(균P<0.01);여담고순조비교,록화혈홍소간예현저증고HO-1표체、CO생성량,이현저강저ET-1표체(균P<0.01),자원계람9현저강저HO-1표체、CO생성량,이현저증고ET-1표체(균P<0.01).결론 HO-1/CO계통구유예방동맥죽양경화반괴형성적작용,기궤제가능여해계통대상화조절NOS/NO계통이급하조ET-1표체종이개선혈관내피공능、억제평활기세포증식유관.
Objective To investigate the effect of heme oxygenase/carbon monoxide (HO-1/CO) system on lipid deposition at aortic intima and the mechanism involved in hyperlipidemic rabbits.MethodsTotally 32 rabbits,were divided into four groups. One group as control. Three groups for the following treatments: 1.5% cholesterol ration (Ch group, n=8); 1.5% cholesterol ration plus HO-1 inducer hemin (Hm group, n=8); and instead of hemin, the HO-1 inhibitor, zinc protoporphyrin Ⅸ (Zn group, n=8) was given by injection into the abdominal cavity. Experiments were lasted for 12 weeks. Rabbit aortas were then isolated as the samples for histopathologic and ultrastructural examination. The protein expressions of HO-1 and endothelin-1(ET-1) were investigated by immunohistochemical staining and Western blot analysis. Results Comparing with the Ch group, rabbits of the Hm group showed a remarkably less extent of lipid deposition at the aortic intima[(17.9±3.0)% vs (54.0±4.2)%], and rabbits of the Zn group had a marked extent of lesion development [(61.1±3.5)%]. Lipid deposition, endothelial damage and neo-intimal formation were less severe in rabbits of the Hm group than those in the Zn or Ch group, respectively. Comparing with the control group, rabbits of the Ch group showed a significant decrease of aortic NO production and cNOS activity. However, there were an enhancement of CO production and HO-1 activity (P<0.01). Compared with Ch group, rabbits of the Hm group showed a remarkable elevation of aortic HO activity and CO production, whereas rabbits of the Zn group showed a marked decrease of both parameters. Compared with the Ch group, rabbits of the Hm group demonstrated a marked reduction of aorta ET-1 expression, whereas Zn group had a significantly higher ET-1 expression. Conclusions Modulation of HO-1/CO system may improve vascular endothelial function and inhibit smooth muscle cell proliferation in hypercholesterolemic rabbits, likely through a compensatory mechanism and a reduction of ET-1 expression, eventually leading to an inhibition of atherosclerotic plaque development.
