冠状动脉结扎致心肌纤维化大鼠模型的建立

目的建立大鼠心肌纤维化（myocardial fibrosis,MF）模型,探讨其病变规律,为临床防治MF研究提供实验动物模型。方法 100只雄性Wistar大鼠随机分为模型组（92只）和伪手术组（8只）,模型组进行心脏冠状动脉结扎（coronary artery ligation,CAL）,手术后第7、14、21、28、35、42、49、56天分别处死;留取心脏标本,HE染色和Masson染色观察心肌组织基本结构,定量测定心脏组织羟脯氨酸含量、心肌胶原和转化生长因子β1（transfor-ming growth factor,TGF-β1）的表达。另设立伪手术组作为对照。结果与伪手术组组相比,模型组大鼠手术7 d后心肌组织炎性反应即已严重,心肌细胞断裂,心肌胶原含量显著升高（P〈0.01）,羟脯氨酸含量升高（P〈0.05）,TGF-β1表达显著增高并持续保持在较高水平（P〈0.01）,纤维化反应在第42天达到高峰,其后有好转趋势。结论 CAL法能成功建立可靠的心肌纤维化动物模型,其机制可能与上调TGF-β1表达有关。

Establishment of a rat model of myocardial fibrosis induced by coronary artery ligation

Objective To establish a rat model of myocardial fibrosis and investigate its pathogenetic characteristics,and provide an animal model of myocardial fibrosis(MF) for clinical research.Method One hundred male Wistar rats were randomly divided into two groups: the model group(n =92) and the sham group(n=8).The rats in the model group were subjected to heart coronary artery ligation(CAL).Heart specimens were taken at different time points from 1 to 8 weeks.Pathological changes and collagen distribution were examined by histopathology using HE and Masson staining.The hydroxyproline content and expression of collagen and TGF-β1 in the heart tissue were quantitatively determined.The sham operated rats served as controls.Results On the 7th day after CAL,compared with the control rats,the heart tissue of rats in the model group showed seveve inflammatory reaction: disrupture and degeneration of cardiomyocytes,significant increase of collagen content(P<0.01),hydroxyproline content(P<0.05),expression of TGF-β1(P<0.01),and those changes were kept at a high level during the experiment.The fibrosis reached a peak on the 42nd day,and then it showed a tendency of improvement.No abnormal changes were seen in the myocardium of control rats.Conclusions A reliable rat model of myocardial fibrosis can be successfully established by coronary artery ligation.Its mechanism may be related to the overexpression of TGF-β1.