小鼠(Bla/J品系)心肌细胞超微结构变化与dysferlin蛋白缺陷相关肌病

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论证在罕见的遗传性肌营养不良——dysferlin蛋白缺陷相关肌病（dysferlinopathy）中，横纹心肌组织的研究较为有限。传统观点认为，该疾病主要影响骨骼肌，由于患者临床上显著的心力衰竭发生率较低，这一观点得到了进一步支持。然而，已有个别研究报道，在遗传性dysferlin缺乏的情况下，心肌也可能受到病理性影响。在这些患者中，心力衰竭的发生可能既与因运动减少导致的血液循环重塑有关，也可能是心肌直接损伤的结果。支持后者的证据包括在Bla/J品系dysferlinopathy模型小鼠中观察到的心肌结构变化。然而，关于该病理过程中心肌细胞及基质细胞（成纤维细胞、内皮细胞、端细胞）的亚微观变化及其在疾病发生中的作用，现有研究仍然不足。

目的。描述Bla/J品系dysferlin缺乏小鼠左心室心肌细胞及基质细胞的超微结构特征。

材料与方法。取3、6、9和12月龄的Bla/J品系小鼠和C57BL/6品系对照小鼠左心室心肌组织，固定后包埋于阿拉尔德树脂，制作厚度为50–100 nm的超薄切片。切片经Reynolds法染色后，采用透射电子显微镜进行观察分析。

结果。在Bla/J品系dysferlin缺乏小鼠的心肌中观察到显著的超微结构变化，包括肌膜和闰盘的破坏、肌质网的扩张和空泡化，以及线粒体形态的多样性。此外，在膜下区和肌质网池中检测到髓鞘样结构。在这些小鼠的心肌基质中，端细胞表现出破坏性变化。而在C57BL/6品系对照小鼠心肌中，未观察到明显的超微结构异常。

结论。在Bla/J品系dysferlin缺乏小鼠中观察到的心肌超微结构损伤，提示dysferlin可能在维持心肌细胞及基质细胞的结构完整性方面发挥重要作用。

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作者简介

Igor S. Limaev

Petrovsky National Research Centre of Surgery

编辑信件的主要联系方式.
Email: is.limaev@proton.me
ORCID iD: 0000-0002-0994-9787
SPIN 代码: 4909-6550
俄罗斯联邦, Moscow

Ivan A. Yakovlev

Genotarget LLC

Email: ivan@ivan-ya.ru
ORCID iD: 0000-0001-8127-4078
SPIN 代码: 8222-2234

MD, Cand. Sci. (Medicine)

俄罗斯联邦, Moscow

Irina A. Chekmareva

Petrovsky National Research Centre of Surgery; A.V. Vishnevsky National Medical Research Center of Surgery

Email: chia236@mail.ru
ORCID iD: 0000-0003-0126-4473
SPIN 代码: 5994-7650

Dr. Sci. (Biology)

俄罗斯联邦, Moscow; Moscow

Sergey N. Bardakov

Military Medical Academy named after S.M. Kirov

Email: epistaxis@mail.ru
ORCID iD: 0000-0002-3804-6245
SPIN 代码: 2351-4096

MD, Cand. Sci. (Medicine)

俄罗斯联邦, Saint Petersburg

Aleksey M. Emelin

Petrovsky National Research Centre of Surgery

Email: eamar40rn@gmail.com
ORCID iD: 0000-0003-4109-0105
SPIN 代码: 5605-1140
俄罗斯联邦, Moscow

Maria A. Savelyeva

North-Western State Medical University named after I.I. Mechnikov

Email: savelyeva.mariaanat@yandex.ru
ORCID iD: 0009-0008-5667-115X
SPIN 代码: 9935-5416
俄罗斯联邦, Saint Petersburg

Alexey V. Deykin

Belgorod National Research University

Email: alexei@deikin.ru
ORCID iD: 0000-0001-9960-0863
SPIN 代码: 8371-5197

Cand. Sci. (Biology)

俄罗斯联邦, Belgorod

Roman V. Deev

Petrovsky National Research Centre of Surgery; Genotarget LLC

Email: romdey@gmail.com
ORCID iD: 0000-0001-8389-3841
SPIN 代码: 2957-1687

Cand. Sci. (Medicine)

俄罗斯联邦, Moscow; Moscow

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2. Fig. 1. Ultrastructure of the left ventricular myocardium in 3-month-old Bla/J mice: a, destruction of myofibrils; ×17,000; b, swollen, enlarged mitochondrion (marked with an asterisk) among mitochondria with electron-dense matrix, ×14,000; c, myelin-like structures in the subsarcolemmal space (marked with an asterisk), ×17,000; d, destructively altered sarcolemma (indicated by black arrows), ×23,000; e, signs of endothelial cell (EN) destruction and myelin-like inclusions (indicated by white arrows), ×14,000; f, telocyte in the stroma adjacent to a cardiomyocyte, ×8,900.

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3. Fig. 2. Aggregates of telocytes in the myocardial stroma of 3-month-old C57BL/6 mice (electron micrograph montage, ×4,000).

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4. Fig. 3. Ultrastructure of the left ventricular myocardium in 6-month-old Bla/J mice: a, mitochondrial polymorphism, ×23,000; b, mild edema in the area of the intercalated disc, ×23,000; c, functionally active fibroblast, ×12,000; d, degenerative changes in telocytes (TC) adjacent to a cardiomyocyte (CM), short telopodes (indicated by arrows) with podoms (arrowheads), ×17,000.

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5. Fig. 4. Ultrastructure of the left ventricular myocardium in 9–12-month-old Bla/J mice: a, myelin-like inclusions (indicated by arrows) in dilated cisterns of the sarcoplasmic reticulum, ×12,000; b, mild edema in the area of the intercalated disc of a cardiomyocyte, ×17,000; c, degenerative telocyte (marked with an asterisk), ×8,900; d, telocyte (indicated by an arrow) in contact with a cardiomyocyte (CM) and an endothelial cell (EN), ×12,000.

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