胸主动脉缩窄术复制压力超负荷兔子模型对心肌细胞增殖、血流动力、心肌成纤维增生及心功能的变化

冯卫中 徐鹏 张金堂

[摘要] 目的 探讨胸主动脉缩窄术复制压力超负荷兔子模型心肌细胞增殖、血流动力、心肌成纤维增生及心功能的变化。 方法 随机选取清洁级健康成年新西兰大白兔60只，将兔子随机分为假手术组及模型组两组，每组兔子30只。假手术组开胸后不结扎胸主动脉，模型组开胸后分离胸主动脉。分别测定各组兔子血流动力学和心功能指标水平、心重指数和心肌细胞体积水平、心肌细胞增殖情况、心肌组織形态变化以及各组心肌胶原含量以及各组血清脑钠肽（BNP）、氨基端前脑钠肽（NT-proBNP）水平。 结果 与假手术组对比，模型组兔子LVSP、LVDP、动脉收缩压及动脉舒张压、BNP、NT-proBNP水平、心重指数、细胞增殖指数均明显升高，心肌细胞体积、CVF-V、CVF-NV含量均明显增加，+dp/dtmax、-dp/dtmax水平均明显减低（P<0.05或P<0.01）。假手术组心肌细胞排列正常，细胞核呈椭圆形，心肌间质无明显增生，心肌纤维走形整齐、结构清晰;模型组部分心肌细胞周围结构不清，细胞核固缩，心肌纤维排列紊乱，纤维增生肥大、断裂。 结论 胸主动脉缩窄术复制压力超负荷兔子模型能够抑制心肌细胞增殖、促进心肌成纤维增生，对兔子血流动力及心功能均产生了严重影响。

[关键词] 胸主动脉缩窄术;压力超负荷;心肌细胞增殖;血流动力;心肌成纤维增生;心功能

[Abstract] Objective To investigate the changes of myocardial cell proliferation， hemodynamics， myocardial fibroblast hyperplasia and cardiac function in rabbits with pressure overload replicated by thoracic aortic coarctation. Methods A total of 60 clean healthy adult New Zealand rabbits were randomly selected and divided into two groups： the sham operation group（n=30） and the model group（n=30）. The sham operation group was not ligated the thoracic aorta after thoracotomy， while the model group was separated the thoracic aorta after thoracotomy. Hemodynamics and cardiac function index level， cardiac weight index and myocardial cell volume level， myocardial cell proliferation， myocardial tissue morphological changes， myocardial collagen content， serum brain natriuretic peptide（BNP） and amino-terminal pro-brain natriuretic peptide（NT-proBNP） levels in each group were measured respectively. Results Compared with the sham operation group， LVSP， LVDP， arterial systolic pressure and diastolic pressure， BNP， NT-proBNP level， cardiac weight index and cell proliferation index in the model group significantly raised. The myocardial cell volume， CVF-V， CVF-NV content were significantly increased， and +dp/dtmax and -dp/dtmax levels were significantly decreased（P<0.05 or P<0.01）. In the sham operation group， myocardial cells were arranged normally， nucleus was oval， myocardial interstitium did not proliferate obviously， and myocardial fibers had regular shape and clear structure. In the model group， the peripheral structure of some myocardial cells was unclear， nucleus shrinked， myocardial fibers were disordered， and fibers proliferated， hypertrophied and fractured. Conclusion The pressure overload rabbit model reproduced by thoracic aortic coarctation can inhibit myocardial cell proliferation and promote myocardial fibroblast hyperplasia， which has a serious impact on rabbits′ hemodynamics and cardiac function.

[Key words] Thoracic aortic coarctation; Pressure overload; Myocardial cell proliferation; Hemodynamics; Myocardial fibroblast hyperplasia; Cardiac function

心肌肥厚是心肌对高血压、瓣膜病、急性心肌梗死等多种原因造成的压力或容量超负荷的一种基本应答，主要表现为心肌细胞体积增大、心肌间质组织增生等，使心脏的顺应性及循环泵功能明显降低[1]。研究发现，心肌肥厚与多种心血管疾病的发展过程密切相关，其在代偿初期往往能够维持正常的室壁张力，但长期的心肌肥厚会明显增加心衰和猝死的发生率，心肌肥厚可作为心肌缺血、心律失常以及猝死等的独立危险因素[2]。心肌肥厚是一个复杂的病理过程，其发生机制尚不明确，认为主要与心肌负荷过重、心肌坏死纤维化、心肌细胞凋亡、神经内分泌、基因改变以及环境等因素有关[3]。……