Utrophin, MHC and M1/M2 macrophages in GRMD dogs

Abstract Muscular dystrophies are hereditary diseases that lead to progressive degeneration of the skeletal musculature. Golden Retriever dogs are used as animal models because they show a hereditary muscle disease similar to muscular dystrophy in humans. Aims: To evaluate the immunostaining of M1 (CD68) and M2 (CD163) macrophages, MHC I, MHC II and, utrophin in muscles of Golden Retriever dogs affected by muscular dystrophy (GRMD). Methods: Samples from 17 male dogs affected by GRMD were divided into GI - dystrophic dogs up to one year of age; and GII - dystrophic dogs over one-year-old. Results: Immunostaining of CD163 was higher than CD68 in both GI and GII. CD68 showed no variation between groups of dystrophic animals. MHC class I immunostaining was most evident in the biceps femoris and triceps brachialis. MHC class II was expressed mildly in four dystrophic muscle types in GI and GII. Utrophin immunostaining was higher in GII. Conclusion: M2 macrophages were one of the main mononuclear inflammatory cells found in dystrophic muscles. The number of M2 in muscles of dogs with GRMD increases with age, linking this cell subtype to permanent muscle damage.摘要 肌营养不良症是一类可导致骨骼肌进行性退变的遗传性疾病。金毛寻回犬常被用作该类疾病的动物模型，因其可自发患上与人类肌营养不良症高度相似的遗传性肌肉病变。 研究目的：评估患金毛肌营养不良症（Golden Retriever Muscular Dystrophy, GRMD）的金毛寻回犬肌肉组织中，M1巨噬细胞（CD68标记）、M2巨噬细胞（CD163标记）、主要组织相容性复合体I类（MHC I）、主要组织相容性复合体II类（MHC II）以及肌调蛋白（utrophin）的免疫染色特征。 研究方法：纳入17只确诊GRMD的雄性金毛犬样本，按年龄分为两组：GI组为1岁及以下的营养不良症患犬，GII组为1岁以上的营养不良症患犬。 研究结果：GI组与GII组中，CD163的免疫染色强度均高于CD68；CD68的免疫染色水平在两组患犬间无显著差异。MHC I的免疫染色在股二头肌与肱三头肌中最为显著。GI组与GII组中，MHC II在四种受累肌肉组织中均呈轻度表达。GII组的肌调蛋白（utrophin）免疫染色强度更高。 研究结论：M2巨噬细胞是退变营养不良肌肉组织中主要的单核炎性细胞之一；GRMD患犬肌肉组织内的M2巨噬细胞数量随年龄增长而升高，提示该细胞亚型与永久性肌肉损伤存在潜在关联。