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目的通过观察结蛋白相关心肌病(desmin-relatedcardiomyopa-thy,DRC)转基因小鼠桥粒相关蛋白表达和分布的变化,以探讨其发病机制。方法应用Western印迹和免疫标记共聚焦显微镜观察桥粒斑蛋白(desmoplakin,DP)和plakoglobin(PG)在1个月小鼠心室肌组织中的表达和分布。结果突变型结蛋白转基因小鼠(D7-des)较野生型结蛋白转基因小鼠(WT-des)和非转基因小鼠(NTG)DP总蛋白和细胞骨架蛋白部分(TIF)明显升高,免疫标记心肌组织DP分布在细胞的两端、侧面和胞质,且密度显著增加,而WT-des与NTG比较无明显变化;3组动物之间,PG没有变化;免疫标记显示D7-des结蛋白排列紊乱,失去正常的结构。结论该研究首次发现突变结蛋白破坏了结蛋白和桥粒结构的完整性,影响了心肌细胞机械耦联,可能与DRC舒缩功能异常和心力衰竭的发生有关。
Objective To investigate the pathogenesis of desmosome-related cardiomyopathy (desmin-related cardiomyo-thy (DRC) transgenic mice by analyzing the expression and distribution of desmosome-related proteins. Methods The expression and distribution of desmoplakin (DP) and plakoglobin (PG) in ventricular myocytes of 1 month were observed by Western blotting and immunofluorescence confocal microscopy. Results The total protein and cytoskeleton portion (TIF) of mutant total protein (D7-des) in WT transgenic mice (WT-des) and non-transgenic mice (NTG) Marked myocardial tissue DP distribution in the cells at both ends, side and the cytoplasm, and the density increased significantly, while WT-des and NTG no significant change; between the three groups of animals, PG did not change; immune markers showed D7-des desmin Disorderly arranged, loss of normal structure. Conclusions This study, for the first time, found that mutant desmin can disrupt the integrity of desmin and desmosome structure and affect the mechanical coupling of cardiomyocytes, which may be related to the dysfunction of DRC contraction and heart failure.