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目的进一步在动物模型水平验证乙醛脱氢酶2(ALDH2)能否通过抑制心肌细胞凋亡实现保护心脏功能的作用。方法实验分ALDH2心脏敲除和心脏高表达两个部分进行,从正、反角度观察ALDH2在心力衰竭发展过程中的作用。引进ALDH2基因敲除小鼠模型(6只),以C57BL／6小鼠作为对照;并建立ALDH2心脏高表达的小鼠模型(采用主动脉结扎法注射ALDH2的腺病毒颗粒),以注射携带空质粒腺病毒的小鼠作为对照组(5只)。对小鼠分别结扎冠状动脉前降支,术后1个月运用超声及导管的方法观察小鼠心脏功能,TUNEL检测心肌细胞凋亡情况。结果ALDH2基因敲除的小鼠与对照组C57BL／6小鼠比较,心脏明显扩大,左室射血分数(LVEF)明显下降(P<0．05),左室舒张末压(LNEDP)明显上升(P<0．05),TUNEL方法显示凋亡的心肌细胞数目明显增多(P(O．05)．相反,ALDH2心脏高表达的小鼠与对照组比较,梗死面积缩小,左室舒张末期内径(LVEDD)明显减小(P<0．05),LVEF和左室短轴缩短率(FS)明显升高(P值均<0．05), TUNEL方法显示凋亡的细胞数目明显减少(P<0．01)。结论ALDH2基因敲除的小鼠与对照组比较心功能恶化,心肌细胞凋亡增多;而ALDH2心脏高表达的小鼠心脏重构却得到改善,心脏功能提高,心肌细胞凋亡减少。ALDH2确实通过减少心肌细胞凋亡而抑制心力衰竭的发展过程。
Objective To further verify whether aldehyde dehydrogenase 2 (ALDH2) could protect cardiac function by inhibiting cardiomyocyte apoptosis at the animal model level. Methods The experiment was divided into two parts: ALDH2 heart knockout and high heart expression, and the role of ALDH2 in the development of heart failure was observed from the positive and negative angles. The mice model of ALDH2 knockout (6 mice) was induced by C57BL / 6 mice and the mouse model of ALDH2 heart hypersplenism (ALDH2 injection of adenovirus particles by aortic ligation) was established. Plasmid adenovirus mice served as control group (5 mice). Ligation of the anterior descending coronary artery was performed in mice respectively. The cardiac function of the mice was observed by ultrasound and catheter 1 month after operation. The apoptosis of cardiomyocytes was detected by TUNEL. Results Compared with C57BL / 6 mice, the ALDH2 gene knockout mice had significantly enlarged heart, LVEF (P <0.05), and significantly increased left ventricular end diastolic pressure (LNEDP) (P <0.05). The number of apoptotic cardiomyocytes was significantly increased by TUNEL assay (P <0.05) .Conversely, compared with the control group, the mice with ALDH2 cardiac hypertrophy had smaller infarct size, (P <0.05), LVEF and left ventricular fractional shortening (FS) were significantly increased (P <0.05), and the number of apoptotic cells was significantly decreased by TUNEL method (P <0.01) .Conclusion The ALDH2 knockout mice showed worse cardiac function and increased cardiomyocyte apoptosis compared with the control group, while cardiac remodeling was improved in mice with high ALDH2 heart expression and cardiac function ALD2 indeed inhibits the development of heart failure by reducing cardiomyocyte apoptosis.