筋ジストロフィー症の発症機序に関する研究—ジストロフィー鶏におけるthiobarbituric acid反応物質の検討

STUDIES ON PATHOGENESIS OF MUSCULAR DYSTROPHY:LEVELS OF THIOBARBITURIC ACIDREACTIVE PRODUCTS IN AVIAN MUSCULAR DYSTROPHY

　抄録　筋ジストロフィー症の発症機序に関する研究の一環として，活性酸素が筋細胞変性過程における細胞障害に関与しているかどうかを検討する目的で，ジストロフィー鶏をモデルとして，浅胸筋のthiobarbi—turic acid （TBA）反応物質を測定した。活性酸素は脂質の過酸化を促進し，TBA反応物質は，この脂質過酸化の際生ずるmalondialdehyde （MDA）量を反映するとされている。New Hampshire系ジストロフィー鶏および対照鶏の受精卵を入手孵化後2週目，4週目，4力月目に断頭屠殺，各々の浅胸筋ホモジェネートのTBA反応物質を測定比較したが，いずれも対照に比しジストロフィー鶏において有意な上昇が認められ，発育早期より脂質の過酸化が亢進していることが明らかとなった。この結果は，筋細胞障害に活性酸素が関与している可能性を示唆するものと考えられる。

Lipid peroxidation and other free radical reac-tions are known to disrupt and damage cellular structures and function, and it has been postulated as possible mechanisms of cellular damage of mus-cular dystrophy because increased levels of thio-barbituric acid (TBA)-reactive products and in-creased activities of superoxide dismutase and glutathione peroxidase were reported in avian muscular dystrophy. We reported that activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase were signifi-cantly increased in avian muscular dystrophy from the early developmental stage. Since these enzymes protect cellular structures from free radicals and peroxides, increased activities of these enzymes would indicate increased formation of radicals.

Then it seems to be important to assay TBA-reactive products which indicate tissue malondi-aldehyde content, a by-product of lipid peroxidation. We used dystrophic chickens of New Hampshire series line 413 and their controls line 412 for as-say of TBA-reactive products. Four or five birds from respective lines were killed by decapitation two weeks, four weeks and four months after hatching. The superficial pectoral muscle was im-mediately weighed and levels of TBA-reactive products in the muscle homogenate was assayed by fluorophotometry according to the modified method of Ohkawa and Tanizawa.

Levels of TBA-reactive products were significant-ly higher in dystrophic chickens at all stages of development studied than those of the control group. At two weeks of age morphological changes are minimum if present and increased levels of TBA-reactive products cannot be considered as a secondary change of morphological alterations. Therfore, the results indicate involvement of lipid peroxidation damage in pathogenesis of this avian muscular dystrophy. Increased lipid peroxidation is probably a result of increased turnover of active oxygen species which was reported previously.