中国病理生理杂志
中國病理生理雜誌
중국병리생리잡지
CHINESE JOURNAL OF PATHOPHYSIOLOGY
2010年
4期
669-675
,共7页
刘军妮%徐冬玲%杜贻萌%蒋卫东%王欣%董兆强%陈良%胡晓波%王光允%许复郁%赵敬杰%郝琳%王群%鹿庆华
劉軍妮%徐鼕玲%杜貽萌%蔣衛東%王訢%董兆彊%陳良%鬍曉波%王光允%許複鬱%趙敬傑%郝琳%王群%鹿慶華
류군니%서동령%두이맹%장위동%왕흔%동조강%진량%호효파%왕광윤%허복욱%조경걸%학림%왕군%록경화
脂蛋白相关磷脂酶A_2%超敏C反应蛋白%基质金属蛋白酶9%动脉粥样硬化%易损斑块
脂蛋白相關燐脂酶A_2%超敏C反應蛋白%基質金屬蛋白酶9%動脈粥樣硬化%易損斑塊
지단백상관린지매A_2%초민C반응단백%기질금속단백매9%동맥죽양경화%역손반괴
Lipoprotein-associated phospholipase A_2%High sensitive C-reactive protein%Matrix metalloproteinase-9%Atherosclerosis%Vulnerable plaque
目的:建立易损斑块动物模型,观察探讨脂蛋白相关磷脂酶A_2(Lp-PLA_2)、超敏C反应蛋白(hs-CRP)、基质金属蛋白酶(MMP-9)在易损斑块中的表达规律.方法:实验新西兰雄兔48只随机分为对照组、稳定斑块组、p53基因组和p53+药物组.对照组假手术后普通饲料喂养;稳定斑块组、p53基因和p53+药物组行腹主动脉球囊拉伤后高脂喂养12周,p53基因和p53+药物组于10周末行腹主动脉斑块形成处转染人野生型p53基因重组腺病毒载体,p53+药物组于12周末给与中国圆斑蝰蛇毒和组胺药物触发斑块破裂.4组兔于实验第1 d和处死前检测Lp-PLA_2、hs-CRP、MMP-9、HDL、LDL、VLDL血清指标,处死后取腹主动脉斑块处病理标本并做局部原位杂交、免疫组织化学分析.结果:稳定斑块组、p53基因组和p53基因+药物触发组血清Lp-PLA_2、MMP-9第12周末明显高于对照组和实验第1 d(P<0.05);p53基因组和p53基因+药物触发组血清Lp-PLA_2及hs-CRP水平明显高于对照组和稳定斑块组,差别显著(P<0.05);p53基因+药物触发组与p53基因组比较血清Lp-PLA_2、hs-CRP、MMP-9水平均差别明显(P<0.05).第12周末,病理结果示4组兔分别为正常动脉血管、稳定粥样硬化斑块、易损斑块、破裂斑块模型,在p53基因组和p53基因+药物触发组纤维帽厚度明显低于稳定斑块组(P<0.05);p53基因+药物触发组斑块破裂、血栓形成明显高于p53基因组.血清Lp-PLA_2与斑块纤维帽厚度呈明显负相关性(r=-0.710,P<0.01),hs-CRP、MMP-9与纤维帽厚度无明显相关关系(P>0.05).结论:在已建立的动脉粥样硬化动物易损斑块模型上,动脉血清与组织Lp-PLA_2、hs-CRP、MMP-9的表达规律表明,Lp-PLA_2与斑块的不稳定性相关性好,结合hs-CRP、MMP-9检测可更好阐释斑块的性质;为发现易损斑块并预测斑块稳定性提供了基础实验依据.
目的:建立易損斑塊動物模型,觀察探討脂蛋白相關燐脂酶A_2(Lp-PLA_2)、超敏C反應蛋白(hs-CRP)、基質金屬蛋白酶(MMP-9)在易損斑塊中的錶達規律.方法:實驗新西蘭雄兔48隻隨機分為對照組、穩定斑塊組、p53基因組和p53+藥物組.對照組假手術後普通飼料餵養;穩定斑塊組、p53基因和p53+藥物組行腹主動脈毬囊拉傷後高脂餵養12週,p53基因和p53+藥物組于10週末行腹主動脈斑塊形成處轉染人野生型p53基因重組腺病毒載體,p53+藥物組于12週末給與中國圓斑蝰蛇毒和組胺藥物觸髮斑塊破裂.4組兔于實驗第1 d和處死前檢測Lp-PLA_2、hs-CRP、MMP-9、HDL、LDL、VLDL血清指標,處死後取腹主動脈斑塊處病理標本併做跼部原位雜交、免疫組織化學分析.結果:穩定斑塊組、p53基因組和p53基因+藥物觸髮組血清Lp-PLA_2、MMP-9第12週末明顯高于對照組和實驗第1 d(P<0.05);p53基因組和p53基因+藥物觸髮組血清Lp-PLA_2及hs-CRP水平明顯高于對照組和穩定斑塊組,差彆顯著(P<0.05);p53基因+藥物觸髮組與p53基因組比較血清Lp-PLA_2、hs-CRP、MMP-9水平均差彆明顯(P<0.05).第12週末,病理結果示4組兔分彆為正常動脈血管、穩定粥樣硬化斑塊、易損斑塊、破裂斑塊模型,在p53基因組和p53基因+藥物觸髮組纖維帽厚度明顯低于穩定斑塊組(P<0.05);p53基因+藥物觸髮組斑塊破裂、血栓形成明顯高于p53基因組.血清Lp-PLA_2與斑塊纖維帽厚度呈明顯負相關性(r=-0.710,P<0.01),hs-CRP、MMP-9與纖維帽厚度無明顯相關關繫(P>0.05).結論:在已建立的動脈粥樣硬化動物易損斑塊模型上,動脈血清與組織Lp-PLA_2、hs-CRP、MMP-9的錶達規律錶明,Lp-PLA_2與斑塊的不穩定性相關性好,結閤hs-CRP、MMP-9檢測可更好闡釋斑塊的性質;為髮現易損斑塊併預測斑塊穩定性提供瞭基礎實驗依據.
목적:건립역손반괴동물모형,관찰탐토지단백상관린지매A_2(Lp-PLA_2)、초민C반응단백(hs-CRP)、기질금속단백매(MMP-9)재역손반괴중적표체규률.방법:실험신서란웅토48지수궤분위대조조、은정반괴조、p53기인조화p53+약물조.대조조가수술후보통사료위양;은정반괴조、p53기인화p53+약물조행복주동맥구낭랍상후고지위양12주,p53기인화p53+약물조우10주말행복주동맥반괴형성처전염인야생형p53기인중조선병독재체,p53+약물조우12주말급여중국원반호사독화조알약물촉발반괴파렬.4조토우실험제1 d화처사전검측Lp-PLA_2、hs-CRP、MMP-9、HDL、LDL、VLDL혈청지표,처사후취복주동맥반괴처병리표본병주국부원위잡교、면역조직화학분석.결과:은정반괴조、p53기인조화p53기인+약물촉발조혈청Lp-PLA_2、MMP-9제12주말명현고우대조조화실험제1 d(P<0.05);p53기인조화p53기인+약물촉발조혈청Lp-PLA_2급hs-CRP수평명현고우대조조화은정반괴조,차별현저(P<0.05);p53기인+약물촉발조여p53기인조비교혈청Lp-PLA_2、hs-CRP、MMP-9수평균차별명현(P<0.05).제12주말,병리결과시4조토분별위정상동맥혈관、은정죽양경화반괴、역손반괴、파렬반괴모형,재p53기인조화p53기인+약물촉발조섬유모후도명현저우은정반괴조(P<0.05);p53기인+약물촉발조반괴파렬、혈전형성명현고우p53기인조.혈청Lp-PLA_2여반괴섬유모후도정명현부상관성(r=-0.710,P<0.01),hs-CRP、MMP-9여섬유모후도무명현상관관계(P>0.05).결론:재이건립적동맥죽양경화동물역손반괴모형상,동맥혈청여조직Lp-PLA_2、hs-CRP、MMP-9적표체규률표명,Lp-PLA_2여반괴적불은정성상관성호,결합hs-CRP、MMP-9검측가경호천석반괴적성질;위발현역손반괴병예측반괴은정성제공료기출실험의거.
AIM: To explore the expressive role of lipoprotein-associated phospholipase A_2, high sensitive C-reactive protein and matrix metalloproteinase-9 in vulnerable atherosclerotic plaques in a rabbit model. METHODS: Forty eight New Zealand white male rabbits were randomly divided into 4 groups (12 rabbits each): control group, stable plaque group, p53 group, and p53+drug group. Rabbits in control group were fed with a regular diet and underwent sham operation. Rabbits in stable plaque group, p53 group and p53+drug group underwent balloon induced arterial wall injury and then were fed on a diet with 1% cholesterol. The animals were all fed for 3 months, then the rabbits in p53 group and p53+drug group underwent Ad5-CMV p53 transfection at 10th week. Before killed, the animals in p53+drug group underwent pharmacological triggering with Russell's viper venom (RVV) and histamine to induce the rupture of the atherosclerotic plaques. At the 1st day and before sacrifice, the serum was collected for measuring Lp-PLA_2, hs-CRP, MMP-9, HDL, LDL and VLDL. The expressions of Lp-PLA_2, hs-CRP and MMP-9 in tissues were determined by the methods of hybridization and immunohistochemistry. RESULTS: At the end of 12th week, the serum and tissue levels of Lp-PLA_2 and MMP-9 in stable plaque group, p53 group and p53+drug group were significant different from those in control group and in each group at the first day (P<0.05). The serum levels of Lp-PLA_2 and hs-CRP in p53 group and p53+drug group were significantly higher than those in control group and stable group (P<0.05). The serum levels of Lp-PLA_2, hs-CRP and MMP-9 were all significantly different between p53 group and p53+drug group (P<0.05). At the end of 12th week, pathological results showed that 4 groups were normal artery, stable plaque, vulnerable plaque and rupture plaque, respectively. The fabric cap was thicker in plaque groups than that in normal group (P<0.05). The rupture and formation of thrombus were more significant in p53+drug group than those in p53 group. The serum level of Lp-PLA_2 had negative interrelated relationship with fabric cap in plaque groups (r=-0.710, P<0.01), and hs-CRP, MMP-9 had no interrelated relationships with fabric cap in plaque groups. CONCLUSION: Base on the successful establishment of the atherosclerotic plaque animal model, serum Lp-PLA_2 shows better interrelated relationships to plaques stability. Combination with hs-CRP and MMP-9, we can exactly evaluate the nature of plaques.
