Duchenne筋ジストロフィー症のpreclinical stageにおける筋細胞膜異常について

ALTERATION OF MUSCLE PLASMA MEMBRANE STRUCTURE IN THE PRECLINICAL STAGE OF DUCHENNE DYSTROPHY

I．緒言

　進行性筋ジストロフィー症は遺伝性の進行性筋萎縮症であり，病因は不明であるが今までにvascular theory^5），sick motoneuron theory^10）などが提唱されてきた。また本症においては，とくにそのDuchenne型（以下DMDと略す）で古くより赤血球膜の生理生化学的および形態学的な異常が報告されてきており^{1,9,13,14,20）}，1975年Mokri and Enge^11）およびSchmalbruch^16）によるDMD生主検筋線維の電顕的研究により，筋細胞膜が他の細胞小器官の異常に先がけて部分的に消失し，これが筋線維壊死に連なる初期変化であろうと記載された。その後Carpenter^4）らによつて同様の所見が記述され，Bra—dleyら^2）によつても筋細胞膜のProcion yellowの透過性亢進が報告され，赤血球膜異常とあわせジストロフィー症における膜系の異常がその病因として一躍，脚光を浴びるようになつてきた。

　Freeze-fracture法は膜のhydrohobic interiorから膜を内・外2葉に割り，膜の内面の微細構造を観察するのに適した方法であり³），本症のように膜構築異常が疑われる疾患の場合には格好の適応となる。現在までにもいくつかの研究グループにより，ジストロフィー症生検筋に適応されその結果が報告されてきているが^{8,17,18,22）}，DMDのasymptomatic preclinical caseについての報告は見当らない。

The muscles from two preclinical cases of Duchenne muscular dystrophy (DMD) and six age matched boys were investigated using phase optics and the electron microscope including freeze fracture technique.

One preclinical patient was 2 months old and his elder brother had DMD. The value of serum CPK of this patient was 2,800 units. The other preclinical patient was one year old and had no family history. The value of serum CPK of this patient was 18,940 units.

By phase microscopy, a population of fibers with focal lesions such as patchy areas of rarefaction located either under the surface or less frequently in the depth of the fiber and necrotic fibers were noted in both biopsies from preclinical DMD cases and normal boys. However, the fibers with focal lesions and necrotic fibers of normal biopsies were less frequent and only seen in the peripheral area of the muscle fascicles. Between two preclinical DMD cases, the older patient had more frequentlythe fibers with focal lesions and necrotic fibers than the younger patient.

The common myopathological features of con-ventional electron microscopy were the disruption of plasma membrane overlying the focal lesion.

The freeze fracture study of muscle plasma membrane showed the reduced density of intra-membranous particles (IMP) in both P and E faces of two preclinical DMD cases in comparison with normal boys. The orthogonal arrays density was also less numerous in two preclinical DMD cases than in normal control boys. In addition the IMP density in P face including subunits of orthogonal arrays was more numerous in the younger pre-clinical DMD case than that of the older preclinical case.

These myopathological changes may correspond with the clinical feature that the muscle weakness begins after 2 or 3 years old in patient with DMD but not immediately after birth, and the results of this study indicate that muscle plasma membrane architecture is altered in the preclinical stage of DMD.

(Correspondence should be addressed to Dr. Wakayama whose current address is Showa Uni-versity Fujigaoka Hospital 1-30, Fujigaoka, Midori-ku, Yokohama, 227 Japan.)