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目的:探讨心力衰竭发展过程中心肌细胞自噬是如何变化的。方法:8~10周的雄性C57BL/6小鼠,体重控制在24~26g,经主动脉缩窄(AB)构建心肌肥厚模型,分别于不同时间点(0天、1周、3周、4周及8周)运用超声心动图评估小鼠心功能;Western blot检测心脏组织中LC3B-Ⅱ/GAPDH比值、beclin-1及P62蛋白水平;同时运用电子显微镜检测心肌细胞中自噬小体数量。结果:AB术后第1周,心脏组织中LC3B-Ⅱ/GAPDH及beclin-1的表达下降(P<0.05),心脏组织中p62表达水平升高(P<0.05),这种变化一直持续到术后3周(P<0.05);但在第4周时,LC3B-Ⅱ/GAPDH比值在手术组和非手术组中无明显差异,而手术组心脏组织中beclin-1的表达量较非手术组高;而术后第8周时,LC3B-Ⅱ/GAPDH及beclin-1的表达均升高(P<0.05),p62明显降低(P<0.05)。此外,运用电子显微镜检测心脏组织中自噬小体数量,发现AB术后3周内自噬小体减少,第4周时,自噬小体数量开始增多,第8周时明显增多。结论:心肌肥厚过程中,自噬水平下降;AB术后第4周,心功能逐步由代偿转变为失代偿,而在心力衰竭时,心脏组织中自噬水平明显升高。
Objective: To investigate how autophagy changes in cardiomyocytes during the development of heart failure. Methods: Male C57BL / 6 mice (8-10 weeks old) were enrolled in this study. The body weight was controlled at 24-26g. The model of cardiac hypertrophy was established by aortic constriction (AB). The rats were divided into three groups at different time points Week and 8 weeks). The cardiac function of mice was assessed by echocardiography. The ratio of LC3B-Ⅱ / GAPDH, beclin-1 and P62 in heart tissue were detected by Western blot. Meanwhile, the number of autophagic bodies in cardiomyocytes was detected by electron microscopy. Results: At the first week after AB, the expression of LC3B-Ⅱ / GAPDH and beclin-1 in cardiac tissue decreased (P <0.05) and the expression of p62 in cardiac tissue increased (P <0.05) The ratio of LC3B-Ⅱ / GAPDH was no difference between the operation group and the non-operation group at the 4th week, while the expression of beclin-1 in the operation group was significantly lower than that of the non-operation group The expression of LC3B-Ⅱ / GAPDH and beclin-1 at the 8th week after operation increased (P <0.05) and p62 decreased significantly (P <0.05). In addition, using electron microscopy to detect the number of autophagosomes in heart tissue, it was found that autophagosomes were reduced within 3 weeks after AB. At 4 weeks, the number of autophagic bodies began to increase, and significantly increased at the 8th week. CONCLUSION: The level of autophagy decreased during cardiac hypertrophy. In the fourth week after AB, cardiac function gradually changed from decompensation to decompensation, while in heart failure, the level of autophagy was significantly increased.