ラット心筋虚血再灌流障害における抗好中球モノクロナール抗体Urge−8の心筋障害の軽減効果について

Protective Effects of Anti-neutrophil Monoclonal Antibody “Urge-8” against Myocardial Ischemia/Reperfusion Injury in Rats

　〔目的〕ラット心筋虚血再灌流障害モデルに対し抗好中球モノクロナール抗体Urge−8を投与し，障害を軽減できるか否かを検討した．〔材料・方法〕雄性ウイスター系ラットでモデルを作製．実験は1） Control群（C群）：虚血10分前IgG₁抗体投与，2）pre-Urge−8群：虚血10分前Urge−8を250μg/kg投与，3）post-Urge−8群：虚血10分後Urge−8を250μg/kg投与し，1時間虚血24時間再灌流の急性実験で，各群における累積生存率，24時間後の摘出心の梗塞巣（TTC染色）および心筋への好中球浸潤程度を検討した．〔結果〕Urge−8抗体は梗塞巣の縮小（約30％）を認めた．C群に比べてUrge−8抗体投与群は浸潤程度の強い症例が有意に少なかったが，累積生存率は3群に有意差は認めなかった．〔結語〕抗好中球モノクロナール抗体Urge−8は心筋虚血再灌流障害の軽減に有効であった．

　Background : Neutrophil activation initiates myocardial ischemia/reperfusion (I/R) injuries. The aim of this study is to evaluate in vitro functions of our anti-neutrophil monoclonal antibody, Urge-8, and its therapeutic efficacy against myocardial ischemia (MI).

　Methods : We measured in vitro functions of rat neutrophils including chemotactic activity, superoxide production, phagocytic function, and neutrophil degranuration. MI was induced in Wistar rats by clamping the left coronary artery for 1 hr. A total of 60 rats received either IgG₁ (control group. n =20), 250,ug/kg of Urge-8 befor (pre-treatment group, n=20), or after (post-treatment group, n= 20) MI. The three groups were compared during the first 24 hr after reperfusion myocardial neutrophil infiltration, survival rate, and size of MI (ratio of infarcted area to area at risk).

　Results : Urge-8 suppressed functions of neutrophil including chemotactic activity, superoxide production. phagocytic function, and neutrophil degranuration. The Urge-8 treated groups showed lower grade of myocardial neutrophil infiltration, and MI size as compared with the control group. The 24-hr survival rate was not different between the three groups.

　Conclusion : Urge-8 is effective against myocardial I/ R injury by suppressing neutrophil functions and myocardial neutrophil infiltration in rats.