主动脉瓣关闭不全法建立新西兰兔心衰模型

Establishment of a rabbit model of heart failure by aortic regurgitation

目的用主动脉瓣关闭不全法致新西兰兔心衰模型。方法运用导管术造成新西兰兔主动脉瓣膜关闭不全,制作超容量负荷型心衰模型。观察动物的毛色、精神状态、活动情况、饲料消耗指数、体重增加指数、呼吸频率等指标对该模型进行评价;检测血清SOD活力和MDA含量,判断模型组动物机体抗氧化能力;利用酶联免疫法检测血清中c AMP、c GMP的变化情况;利用基因芯片技术分析该模型基因表达差异。结果模型动物SBP、DBP和LVSP著性下降,LV+dp/dt和LV±dp/dt明显下降,LVDP显著上升。模型组与正常组比较,毛发枯槁,活动减少,进食减少,反应迟钝,精神萎靡,抓起时反抗减轻。模型组呼吸频率加快;模型组血清SOD活性低于正常组,MDA含量高于正常组;模型组血清c AMP明显低于正常组,c GMP明显高于正常组;利用基因芯片共检测出665个差异基因,其中与心功能较密切相关的基因主要与离子通道、肌收缩、信号转导等功能有关。结论采用主动脉瓣关闭不全法建立兔心衰模型方法可靠。主动脉关闭不全,使心脏前负荷增加,造成左心室舒张末期容积增加,导致左心室扩大肥厚及心力衰竭。心肌组织基因芯片检测结果显示,该模型基因表达出现了一定的变化。

Objective To establish a New Zealand rabbit model of heart failure by aortic regurgitation.Methods Adapting catheterization-induced aortic regurgitation to establish a volume overloat rabbit model of heart failure.The SBP, LVSP, LVDP, LV＋dp/dt and LV ±dp/dt were observed before and after modeling.The successful criteria of heart failure：the LV ±dp/dtmax was decreased more than 40%and the LVDP increased more than 40%, or the LV ±dp/dtmax fell down to less than 40%and the DBP should be decrease more than 40%.Evaluating the model by observing the coat color, mental status, physical activity, calculating the feed consumption index, weight gain index, heart rate, respiration frequency and other indicators.The activity of serum SOD and MDA concentration were assayed to determine the antioxidant capacity of the model animals.Enzyme-linked immunosorbent assay kit was used to detect the serum cAMP and cGMP con-centration.Gene chip technology was used to analyze the difference of gene expression.Results After modeling, the he-modynamic index of SBP, DBP and LVSP were significantly decreased, LVDP was significantly decreased, LVDP was sig-nificantly increased and the LV＋dp/dt and LV ±dp/dt were significantly decreased.Compared with the normal control group, the model animals showed coat withered, less movement, less eating, unresponsiveness, listlessness, and reduced grab resistance after modeling.The respiratory rate of the model group was significantly increased, and this trend was in-creased over time.The serum SOD activity was lower, MDA concentration was higher, cAMP concentration was lower, and cGMP concentration was higher in the model group.665 differentially expressed genes were detected.Compared with the human gene sequences, 16 characteristic genes were obtained.In these 16 genes, which were closely related to heart func-tion, were mainly related to ion channels, muscle contraction, and signal transduction function.Conclusions This repor-ted method to establish rabbit model of heart failure by using aortic regurgitation is reliable.The aortic regurgitation increa-ses cardiac preload, than leads to an increase of the left ventricular end-diastolic volume, and finally results in left ventric-ular hypertrophy and heart failure.The results of myocardial tissue gene chip test show that there are some changes in gene expression of the model rabbits.