高同型半胱氨酸血症对大鼠心室重塑的作用

Effect of hyperhomocysteinemia on cardiac remodeling in rats

目的:观察饮食诱导的高同型半胱氨酸血症(hyperhomocysteinemia,HHcy)对大鼠心室重塑的作用及终止饮食诱导后的恢复情况。方法:健康雄性Wistar大鼠分为(1)饮食诱导组(HHcy组):1g／(kg·d)L-蛋氨酸灌胃4周,(2)终止诱导组(Quit hcy,QHcy组):L-蛋氨酸灌胃4周后再普通饲养4周,(3)对照组(Control)分4周组和8周组:饮用水灌胃作为对照。以超声心动图评价心脏结构和收缩功能,苏木素-伊红(HE)、胶原纤维、免疫组化染色观察心脏组织形态、胶原和小血管的变化。结果:血浆同型半胱氨酸(homocysteine,Hcy)浓度HHcy组为 (106．19±19．75)μmol／L,QHcy组为(6．52±0．94)μmol／L,对照组为(4.90±0．10)μmol／L;HHcy组与对照组相比大鼠室壁张力升高62．1％(P<0．01),收缩功能即射血分数(ejection fraction,EF)值下降10．7％(P<0．01),小血管数减少45．9％(P<0．01),小动脉管壁厚度增加2．9倍(P<0.01),心肌细胞横径无增大,心肌间质和血管壁周围胶原增多;QHcy组与HHcy组相比大鼠室壁张力降低27．6％(P<0．01),但与对照4周组和8周组相比仍分别高于17．3％和27．1％(P<0．01);QHcy组与HHcy组相比心脏收缩功能恢复,即EF值提高14．0％(P<0．01), 与对照组比较差异无统计学意义,QHcy组与HHcy组相比心肌细胞横径增加11．9％(P<0．01),与对照组相比增加15．4％(P<0．01),QHcy组与HHcy组相比小血管数回升79．1％(P<0．01),与对照组相比差异无统计学意义, QHcy组与HHcy组相比小动脉管壁厚度和胶原改变无改善。结论:高同型半胱氨酸能引起大鼠心室重塑,胶原纤维化,室壁张力升高,收缩功能降低。终止饮食诱导后4周血浆Hcy浓度能降低,但心脏重塑的改变未完全逆转。

Objective： To study the effects of hyperhomocysteinemia on cardiac remodeling and systolic function. Methods： Twenty-four Wistar rats were divided randomly into experiment and control group. 12 rats of experiment group were bred with 1 g/（ kg · d） L-methionine. After 4 weeks, 6 of them were killed （ HHcy）, others were continuously bred with normal diet for 4 weeks （ Quit hcy, QHcy）. Twelve rats of control group with normal diet for 4 and 8 weeks. The plasma Hcy concentrations were measured by immuno-fluorescence technique. Left ventricular structure and systolic function were assessed by echocardiography. The cardiac morphology and collagen were studied by optical microscopy and image analysis system after hematoxylin eosin-staining and picrosirius red-staining. Immuno-histochemistry for actinsmooth muscle and factor VⅢ-related antigen was performed to identify changes in cardiac smaller arteriolar and microvascular numbers. Results： The plasma Hcy concentration was （ 106.19 ± 19.75 ） μmol/L in HHcy, （6.52 ±0.94） μmol/L in QHcy and （4.90 ±0.10） μmol/L in the control. Left ventricular systolic function was decreased 10.7% in HHcy. Left ventricular wall strain and cardiac smaller arteriolar wall thickness were increased by 62.1% and 2.9 fold in HHcy, 27.1% and 2.4 fold in QHcy as compared with the control. Cardiomyoeyte diameter was not changed in HHcy and increased by 15.4% in QHcy as compared with the control. Microvascular number was decreased by 45.9% in HHcy as compared with the control, but smaller arteriolar number did not differ among the groups. Left ventricular systolic function and microvascular number resumed in QHcy. Intertitial and perivascular collagen deposition was significantly increased in HHcy and QHcy. Conclusion： Hyperhomocysteinemia may increase cardiomyocyte diameter, cardiac smaller arteriolar wall thickness and left ventricular wall strain; decreasemicrovascular number; induce intertitial and perivascular collagen deposition, directly and indirectly affect on cardiac remodeling and systolic function. The cardiac remodeling couldnt resume completely with plasma Hcy concentration being decreased.