20_Tronov.dvi

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1 131 7 ｧ ｪ ｯ. 12, 02 1(192). ｮ ｷ ｷ31 76ｧ ｷ300, ｧ ｷ300 0ｷ ｭ ｭ6 70ｷ3ｨC0ｷ ｷ3 ｮ ｮ6ｧ8 ｭ ｷ3 ｭ ｯ0ｷ ｯ6 5 ｭ ｯ1 7 ｮ ｭ ｯ ｪ1 7 ｯ070ｷ3 066ｧ81 76ｦ01 7 ｰ 036ｧ90ｹ0 ｭ ｧ8 ｰ ｪ ｭ1 70ｷ3 ｭ ｯ ｷ3: ｮ6 5006ｦ004 ｮ 1 7 ｭ ｨC0ｷ3 ｭ ｷ3 060ｷ31 7 ｭ6ｧ ｱ1 7 ｯ ｭｨC ｭ1 7 ｯ ｧ96ｦ1 076ｧ8 ｭ ｯ ｯ ｦﾌ07ｦﾌ04, 03, ｧ07ｦﾌ05 隕ﾌ04 03, 1, ｦﾌ0905 ｧ0700 ﾀ 00 04, ｭ. 0ｷ ﾀ 00ｦﾌ04 05, ｦﾌ0400 ﾀ ｧ 03, 05 0ｷ ｧ ｧ06 ｧ ﾀｦﾌ 09 ｧ ｧ ﾀ ｧ ｧ ｮ ｦﾌ , 03ｦﾌ00 ﾀ 陦ｧ ｧ ｧ 閨 ｧ 隕ﾌ04 07 ｧ, ｷ ｧ ｧｦﾌ05ｦﾌ05 ｧ ｧ 04 ｧ07 ｧ00 ｧ ｦﾌ050701ｦﾌ , 03ｦﾌ00 ﾀ ｷ ｧ ｧｦﾌ00 ｧ06 ｧ ﾀｦﾌ 09 ｧ ｧ ﾀ ｧ ｧ , 03ｦﾌ00 ﾀ04 ｮ ﾀ 03 ｧ ｦﾌ 05 07, 07 00ｦﾌ 閨0004 ｧ 縺 ｦﾌ0007ｦﾌ000707ｦﾌ ｦﾌ04 ｧ ｧ0407ｦﾌ05ｦﾌ 04ｦﾌ 閨06 縺 ｧ00 ｦﾌ ﾀ 閨06, 0207ｦﾌ 閨09ｦﾌ ｦﾌ04 07 ｧ ｧ ｧ 06ｦﾌ04 04 ｧ0706 ｧ 04ｦﾌ ｦﾌ ｧ ｦﾌ 閨 閨0607 ｧ ｦﾌ05ｦﾌ ｧ02 ｧ06 08 ﾀ050607ｦﾌ ﾀ ﾀ ｧ ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀｦﾌ05ｦﾌ 09ｦﾌ- ｦﾌ05 ｧ 0907 ｧ0407ｦﾌ05ｦﾌ ｦﾌ ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀｦﾌ06 04ｦﾌ 閨06 縺 ｧ ｦﾌ 03ｦﾌ ｦﾌ 閨0605 ｧ ( ｧ0507 ｧ07 ｦﾌ ｦﾌ06ｦﾌ ｧ07 )- ｧ07 閨0801 ｧ ｦﾌ ｦﾌ 閨 ｧ ｧ ﾀ ｧ ｧ 隕ﾌ04 05 ｧ ｧ ｦﾌ ﾀ ｧ in vivo 07 ｦﾌ ｧ06 09 ｦﾌ07ｦﾌ07 06 ｧ ｧ ｧ ｧ ﾀ050607ｦﾌ ﾀ ｦﾌ ﾀ 05 ｧ, 0207ｦﾌ 04ｦﾌ ｦﾌ ｧ ﾀ ｧ 09ｦﾌ 閨06 縺 ｧ ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀ ｧ ｦﾌ04, ｧ07 閨0801 ｧ ｧ 閨 ｧ09, ﾀｦﾌ 0605 ｧ ｦﾌ ｧ ﾀ07 ｧ0407ｦﾌ0007 ｧ ｧ ｧ ｦﾌ 閨0607 ｧ ｧ 0007 ｧ ｧ ｧ ｧ 09ｦﾌ07ｦﾌ ｦﾌ ﾀ050607ｦﾌ ﾀ ﾀ Retina, the visual organ, that is permanently undergone aggressive environmental inuence. This implies the existence in retina of intrinsic protective and recovery mechanisms. The presence of retinal genotoxic threshold, nonlinear dose response and adaptive response of retina to genotoxicants suggest this assumption. In this article, using the model of MNU-induced degeneration of retina in mice, we investigated the adaptive response of the retina in vivo after proton irradiation and a participation of Muller glial cells in it. It was showed that the retinal recovery after the genotoxic isults correlated with increase ef ｦcacy of DNA-damage repair and decrease in death of retinal photoreceptor cells. PACS: j; dh ｭ6 7 ｭ1 70ｷ3 ｭ ｮ ﾀ 03 ｦﾌ ｧ ｦﾌ 00 ｧ , 00ｦﾌ0007ｦﾌ0004 ｧ ｧ ｧ ｦﾌ 陦ｧ ｧ ｦﾌ ﾀ050607ｦﾌ ﾀ, ｧ0403 ｧ ｦﾌ00ｦﾌ0307ｦﾌ ﾀ 閨 ｧ09. ｮ ﾀ ﾀ0706 ｧ ｦﾌ ﾀｦﾌ ｦﾌ 縺02 ｧ04ｦﾌ ﾀ 04ｦﾌ 閨06 縺 ｧ0006 ｦﾌ ﾀ 閨06, 04 ﾀ ｧ06 ｧ ﾀ ｧ ｧ ｧｦﾌ07 ｧ- ｧ 陦ｧ 01 ｧ09 [1, 2] , ｧ ﾀｦﾌ0707 ｧ 閨06 ｦﾌ ﾀ vinojv@jinr.ru

2 13242 ｯ ｦﾌ07ｦﾌ ｧ 陦 ｧ ｧ ｧ, ﾀｦﾌ05 08 ｦﾌ ｦﾌ ﾀ00 ｧ ﾀｦﾌ05ｦﾌ 04ｦﾌ 閨06 縺 ｧ ﾀ ｦﾌ ｦﾌ 縺02 ｧ04ｦﾌ0007 ｧ 05 ｧ03ｦﾌ 07 ｧ09 04ｦﾌ 閨06 縺 ｧ ｧ ｯ ﾀ ｧ00 00 ｧ ｧ, 09ｦﾌ ﾀ , 07 ｧ: 陦ｧ 01 ｧｦﾌ ｧ00 ｦﾌ090800ｦﾌ ｦﾌ 05 ｧ ｦﾌ090800ｦﾌ ( 0607 ｧ07ｦﾌ ｦﾌ0606 ｧ ｦﾌ ); 09ｦﾌ ｦﾌ0406 ﾀ 04 ﾀｦﾌ0006ｦﾌ00; 01 ｧ07ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀ ｧ06 ｧｦﾌ ｧ00 ﾀ 陦ｧｦﾌ ｧ ﾀｦﾌ05ｦﾌ ﾀ ｧ0007ｦﾌ ｧ 閨 ﾀ ｦﾌ0706 ﾀ, ｧ ﾀ07 ｧ00, ﾀｦﾌ06, ｦﾌ 0505, ﾀ 07 ﾀ07 [3026]. 1 7 陦ｧ 01 ｧｦﾌ0707ｦﾌ- ｧ07 閨0801 ｧ ｦﾌ ｦﾌ05ｦﾌ05 ｧ ｧ ｧ ｧ 09 ﾀ01 ｧｦﾌ07 ｧ ｦﾌ ｦﾌ06 ｦﾌ ｧ ｧ [7]. ｮ07 ｧ ｧ06 隕ﾌ 06 04ｦﾌ 09 ﾀ01 ｧ0000 ｧ ｧ ｧ06 ｧ ｦﾌ ﾀ01 ｧ0006 ｧ ｧ02 ｧ ｦﾌ000707ｦﾌ ｧ ｦﾌ 07 ﾀ 07 ｧ ｧ ﾀ ｧ ﾀ 04ｦﾌ ｦﾌ ｧ09 [8]. 1 7ｦﾌ0807ｦﾌ ｧ06 09ｦﾌ ﾀ ｦﾌ ｦﾌ ｧ ﾀ ｧ ｦﾌ ｦﾌ ｧ00 09ｦﾌ 04ｦﾌ ｦﾌ0907 ｧ06 ｧ ｧ ｦﾌ ﾀ07 ｧ ﾀ ｧ ﾀｦﾌ05ｦﾌ 04ｦﾌ 閨06 縺 ｧ00 03 隕ﾌ0007 ｧ ｦﾌ ﾀｦﾌ ｧ ﾀｦﾌ ﾀ07 ｧ0407ｦﾌ0007 ｧ 09 ｧ 06 ｧ07 ｧ ｦﾌ06 09ｦﾌ ｧ ｧ 隕ﾌ ｦﾌ ﾀ 0706, 04 07ｦﾌ06 02 ｧ ｧ ﾀ ｧ. 6 5 ﾀｦﾌ0006 ｧ ﾀｦﾌ06 09 ｦﾌ ｦﾌ0007ｦﾌ ｦﾌ ｧ ﾀ ﾀ07ｦﾌ ｦﾌ ｦﾌ07ｦﾌ0706 ｧ ｧ0106 [9]. 1 7 ﾀ 05ｦﾌ0007, 0207ｦﾌ ｦﾌ ｦﾌ space shuttle 09ｦﾌ ｦﾌ ｦﾌ ｦﾌ05ｦﾌ 09ｦﾌ0907ｦﾌ ｧｦﾌ 07ｦﾌ ｦﾌ06 ｧ ｧ ｦﾌ ｧ ｧ ｧ ﾀ ｧ, 04ｦﾌ ﾀ ｧ ﾀｦﾌ07ｦﾌ ｦﾌ ﾀ06, 09 ｦﾌ 閨0801 ｧ ｧ00 ｦﾌ ﾀ ｧ0005 ｧ , 0207ｦﾌ ｧ02 ｧ04 05ｦﾌ ｧ00 ﾀ ｦﾌ ｦﾌ 閨 ｧ ｧ ﾀ ｧ [10]. ｰ 07ｦﾌ04ｦﾌ ｦﾌ07 閨 ﾀ ｦﾌ ﾀｦﾌ0006 ｧ ﾀｦﾌ05ｦﾌ 09ｦﾌ ｧ ｧ- 07 ﾀ ｧ 閨 ｧ ｧ ﾀ ｧ 0505 [11] ｧ ｧ04ｦﾌ ﾀｦﾌ 0605 ｧ ｧ ﾀ07ｦﾌ ｧ ｧ00 ｦﾌ0007 ｦﾌ ｧ00, ﾀｦﾌ07ｦﾌ ｦﾌ06 ｦﾌ % 0007 ｦﾌ ｦﾌ04 09ｦﾌ ｦﾌ050607ｦﾌ04 [12, 13]. ｮ ｧ07ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀｦﾌ 00 ｧ06 ｧｦﾌ ｧ ｧ ﾀ ｦﾌ ｧ ｧ 09 07ｦﾌ05ｦﾌ05 ｧ0006 ｧ 0607 ｧ 閨060607ｦﾌ ｦﾌ05ｦﾌ02 ｧ ｧ ﾀ 01 ｧ (0006. ｦﾌ03 ｦﾌ 06 [14, 15]), 04 ﾀｦﾌ07ｦﾌ ｧ ｦﾌ04, 09 ｦﾌ0306 閨03 ｧ00 ﾀ ｧ06 ｧｦﾌ ｧ ｧ, ｧ ｦﾌ07ｦﾌ09ｦﾌ03 ｧ00, ﾀ 07 ﾀ07, ﾀｦﾌ06, ｧ07ｦﾌ09 07 ｧ00, ｧ ｧ ﾀ 00 閨 ｧ ﾀ ｧ, ﾀ0805ｦﾌ09 07 ｧ00 [16, 17]. 07 ﾀ 04 ｧ 閨07ｦﾌ, 04ｦﾌ ｧ ｧ ｦﾌ ｧ00, 04 ｦﾌ0007ｦﾌ0406 ﾀｦﾌ07ｦﾌ ｦﾌ ｧ07 05 ｧ ﾀ050607ｦﾌ ﾀ ｧ ｦﾌ 00 ｧ ｦﾌ07ｦﾌ ｦﾌ ﾀ050607ｦﾌ ﾀ, 0706 罍 ｦﾌ ﾀ050607ｦﾌ ﾀ, ﾀ050607ｦﾌ ﾀ 09 ｧ ｦﾌ05ｦﾌ 0809 ｧ ｧ ｦﾌ ｦﾌ06 ｧ ｦﾌ ﾀ ｦﾌ 縺02 ｧ04ｦﾌ ﾀ050607ｦﾌ ﾀ ﾀ ｧ 0505 ﾀ ｧ06 04ｦﾌ 閨06 縺 ｧ ｦﾌ ｧｦﾌ0707ｦﾌ 04ｦﾌ 07 ｧ ﾀ03 ｧ ｧ00 ﾀ ﾀ ｧ - 06ｦﾌ ｧ ｧ ｧ 04ｦﾌ ｦﾌ ｧ00, ﾀｦﾌ07ｦﾌ 0606 ｦﾌ ｧ ｧ09 ｧ ｦﾌ 07 ﾀ 07 ｧ ｧ ﾀ01 ｧ ｧ. 1 7 ﾀ ｧ ｦﾌ ﾀ ｦﾌ00ｦﾌ0307ｦﾌ0007 ｧ ﾀ050607ｦﾌ ﾀ/07 ﾀ 07 ｧ ﾀ 04ｦﾌ ｦﾌ ｧ09 ｦﾌ07 09ｦﾌ ｦﾌ 04ｦﾌ 閨06 縺 ｧ ｧ ｦﾌ ｧ0707ｦﾌ ﾀ ｦﾌ ﾀ00 ｧ ﾀｦﾌ05ｦﾌ 04ｦﾌ 閨06 縺 ｧ00, 09ｦﾌ ﾀｦﾌ07ｦﾌ ｦﾌ05ｦﾌ ﾀ ﾀ ｧ/07 ﾀ 07 ｧ 09 ｧｦﾌ ｦﾌ ｦﾌ ﾀ 09ｦﾌ 閨 ｦﾌ 閨06 縺 ｧ ｦﾌ ﾀ00 ｧ ﾀｦﾌ 隕ﾌ 06 [180220] ｦﾌ 03ｦﾌ ｦﾌ 閨0605 ｧ ｧ07 閨0801 ｧ ｦﾌ ｦﾌ 閨 ｧ ｧ ﾀ ｧ [21, 22] 0606 ｧ 隕ﾌ04 05 ｧ 0907 ｧ ｦﾌ ﾀ ｧ 07 ｦﾌ ｧ06 09 ｦﾌ07ｦﾌ07 06 ｧ ( 陦ｧ 01 ｧｦﾌ ｦﾌ ｧ00), ｧ ｧ ﾀ050607ｦﾌ ﾀ ｧ0407ｦﾌ06 ｦﾌ ﾀ ｧ 07 閨06 縺 ｧ ｧ0507 ｧ07 ｦﾌ ｦﾌ06ｦﾌ ｧ0706 ( ), 07 ﾀ ｦﾌ ｧ0007 ｦﾌ ｧ ｦﾌ09 ｦﾌ00: ｦﾌ 05 ｧ 04ｦﾌ ｦﾌ ｧ06 09ｦﾌ 閨06 縺 ｧ ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀ ｧ ｦﾌ ｦﾌ ｧ ｦﾌ00ｦﾌ0307ｦﾌ0007 ｧ ﾀ ｧ ｧ 09ｦﾌ 閨0607 ｧ ｧ 0007 ｧ ｧ ｧ ｧ 09ｦﾌ07ｦﾌ ｦﾌ ﾀ050607ｦﾌ ﾀ ﾀ ｯ ｭ1 70ｷ31 76ｧ86ｧ9 0ｷ3 03 ｭ ｯ ｷ3070ｷ ｧ04ｦﾌ ｷ 隕ﾌ04 07 ｧ00 09 ｦﾌ04ｦﾌ 陦ｧ05 ｧ 07 09ｦﾌ05ｦﾌ04ｦﾌ ｧ03 ｧ 00 CBAxC57Bl, F1 ( ) 04 04ｦﾌ , , ｦﾌ ｧ04ｦﾌ , 00ｦﾌ 閨 ｧ ｦﾌ 07ｦﾌ ｦﾌ04 ｧ0000 ((22 ﾀ 2) 71 ｮ, ｦﾌ0707ｦﾌ00 ｧ ｦﾌ ｦﾌ -

3 130ｷ 隕ﾌ04 07 ｧ ｧ0407ｦﾌ05ｦﾌ ｦﾌ ﾀ ｧ ｦﾌ ｧ06 09 ｦﾌ07ｦﾌ07 06 ｧ 243 閨0800 (60 ﾀ10) % ｧ ｦﾌ04ｦﾌ 0906 ｧｦﾌ ), ｧ ｧ 0004ｦﾌ03ｦﾌ 閨0706 隕ﾌ ﾀ 04ｦﾌ 閨06 ｧ ｧ ｦﾌ ｦﾌ0608 ﾀｦﾌ ｦﾌ0106 閨 ｧ04ｦﾌ ｧ ｧ ｦﾌ ｦﾌ ｦﾌ 09ｦﾌ05ｦﾌ ｧ09 07ｦﾌ06 ｧ ｦﾌ 03 ｧｦﾌ0807 ｧ ﾀ06 0ｷ31 76ｦ1 ｱ ｦﾌ ｧ ｦﾌ 閨 ｧ 07ｦﾌ ｦﾌ0608 ｦﾃ02ｦﾌ ｧ09 ( 60 ｮｦﾌ) 04 隕ﾌ ｧ ﾀｦﾌ ｦﾌ04 ﾀ06 1 7ｦﾌ ﾀ ( 陦ｧ ｧ ｧ 閨 ｧ 隕ﾌ04 07 ｧ, ); 06ｦﾌ0407ｦﾌ ｦﾌ0505ｦﾌ ｦﾌ 隕ﾌ 06 00ｦﾌ ,64 06 /06 ｧ07. 06ｦﾌ05ｦﾌ ｧ04ｦﾌ ｦﾌ ｧ 0800 ﾀｦﾌ ｧ 09 ｦﾌ07ｦﾌ07 06 ｧ 04 隕ﾌ 00 1, 14 ｧ05 ｧ ｦﾌ07 ｦﾌ0706 ( 陦ｧ ｧ ｧ 閨 ｧ 隕ﾌ04 07 ｧ, ) ｧ ｧ ﾀ /0708 ﾀ05ｦﾌ07, 6ｧ = 0,49 ﾀ086 5/06 ﾀ06, 06ｦﾌ0407ｦﾌ 隕ﾌ /06 ｧ 閨0607 ｧ ｧ ｧ ﾀ (Sigma, ｮ0ｹ01 7) ｧ05 ｧ 09 ｧ ｮ, ｦﾌ 0005 ｧ ｧ050707ｦﾌ06 09ｦﾌ ｦﾌ-00ｦﾌ050604ｦﾌ ｦﾌ ｦﾌ 06 (PBS) ｦﾌ00 06 閨 ｦﾌ 閨0607 ｧ ｧ ｧ0707ｦﾌ 隕ﾌ 00 17, 35 ｧ / ﾀ05. 07ｦﾌ0707 ｦﾌ ｧ- 04ｦﾌ ｦﾌ 陦ｧ05 ｧ ｦﾌ PBS, ｧ 0, ｧ05ｦﾌ07ｦﾌ ｧ06 ｦﾌ03 01ｦﾌ04. ｮ ｧ0207ｦﾌ ｦﾌ ｦﾌ 閨06 縺 ｧ00 07 ｧ04ｦﾌ ｧ ｦﾌ ｦﾌ09ｦﾌ 06 ｧ ｧ ﾀ 05 ｧ ｦﾌ ｯ ﾀ ｦﾌ0504 ｧ07ｦﾌ 5 06 ﾀ06 05ｦﾌ07ｦﾌ04 ｧ05 ｧ ｧ 0505, 09 ｧ ﾀ00 ｧ ｦﾌ ｦﾌ ｦﾌ ｦﾌ ｧ ｧ ｦﾌ 閨 ｧ 07ｦﾌ ｦﾌ ﾀ08, ｦﾌ03 03ｦﾌ07 ﾀ ｧ 09 ｧ05ｦﾌ07ｦﾌ ｧ ｦﾌ04 09 ｦﾌ04ｦﾌ 陦ｧ05 ｧ 09ｦﾌ ｦﾌ 09 ｦﾌ0106 閨08 06, ｦﾌ09 ｧ ｦﾌ ｧ [2] ﾀ ﾀ ｧ 閨 ｦﾌ ﾀ0506 ｦﾌ ﾀ 03 ｧ04 05 ｧ ｦﾌ ﾀ00 ｧ05 ｧ07-08ｦﾌ ｧ07ｦﾌ06 ｧ 06 ｧ ﾀ ｦﾌ00 ﾀｦﾌ09 ｧ ｦﾌ04 05 ｧ ｦﾌ00ｦﾌ 閨 ｮ ｧ09 ﾀ050607ｦﾌ ﾀ 05ｦﾌ07ｦﾌ04 ｧ05 ｧ ｧ ｧ ｦﾌ ｧ ｧ04ｦﾌ0707ｦﾌ05ｦﾌ ﾀ ｧ ﾀｦﾌ05ｦﾌ ｧ ﾀｦﾌ05ｦﾌ 陦ｧ ｧ ｦﾌ04 07 ｧ00 07 ﾀ 07 ｧ 04 ｦﾌ 閨060707ｦﾌ06 PBS. 1 7ｦﾌ 閨 ｧ ﾀ05ｦﾌ ｧ ｧ ｦﾌ04 07 ｧ ｧ ｦﾌ04 07 ｧ00 04 ｦﾌ 閨060707ｦﾌ06 PBS 09 ｧ05ｦﾌ07ｦﾌ ｧ09 ﾀ050607ｦﾌ ﾀ ｧ0009ｦﾌ0507 ｦﾌ04 05 ｧ 04 03ｦﾌ ｧ ｧ 01 ｧ00 ﾀ050607ｦﾌ ﾀ ｦﾌ05ｦﾌ 0207ｦﾌ ｦﾌ ｧ ﾀ06 in vivo ｦﾌ0400 ﾀ ｧ06 ﾀ ﾀ ｧ, ｧ0009ｦﾌ0507 ｦﾌ04 05 ｧ 09 ｦﾌ05 ｧ ｧ ﾀ06 BrUdR. 1 7 ｦﾌ0106 閨 ｦﾌ04ｦﾌ 陦ｧ05 ｧ 閨04 07 閨06 04 閨 ｧ (0807 ｦﾌ06 ｧ ｦﾌ06), 0404ｦﾌ 閨00 07 ｧ04ｦﾌ ｧ ｧ0707ｦﾌ ｧ ｦﾌ 06 ﾀ / ﾀ05, ｦﾌ ｦﾌ05ｦﾌ 04 PBS, 04 ｦﾌ < 0, ( ). 1 7ｦﾌ ｧ ｧ00 ｧ ﾀ ｧ ｧ 09 ｧ05ｦﾌ07ｦﾌ ｧ00 06 ｧ ﾀ ｦﾌ00 06 ｦﾌ04 ﾀ ﾀ ｧ, ﾀ ﾀ ｧ ｦﾌ ｧ06 06 ﾀ06, 09 ｦﾌ ｧ 0707 ｧBrUdR 0707 ｧ ｧ, 00 ﾀｦﾌ ｧ ｦﾌ ｧ ｦﾌ ｧ- 07 ｧ ｦﾌ07 ｧｦﾌ01 ｧ 07 07ｦﾌ06 (FITC) ﾀ ｧ 04 ｧ ｧ ｧ ｦﾌ04 05 ｧ 09ｦﾌ ｦﾌ ｧ ｧ FITC 00 09ｦﾌ06ｦﾌ ｦﾌ05ｦﾌ 06 ｧ ﾀ ｦﾌ00 ﾀｦﾌ09 [23]. 1 7ｦﾌ 閨0002 ｧ ｧ 05 ｧ03ｦﾌ 02 ｧ0005ｦﾌ 09ｦﾌ ﾀ0800ｦﾌ 陦ｧ07 ｧ ｦﾌ- 04 陦ｧ 00 06, 05 ｧ03ｦﾌ ｧ ｧ0407ｦﾌ ｦﾌ ｧ ｧ 陦ｧ07 ｧ ｦﾌ04 閨 ｦﾌ06ｦﾌ ｦﾌ ImageJ [24] TUNEL- 閨 ﾀ01 ｧ00 05 ｧ ｧ ﾀ050607ｦﾌ ﾀ ｧ ｧ ｧ 05 ｧ ｧ ﾀ050607ｦﾌ ﾀ ｧ ﾀ ｦﾌ00 ﾀｦﾌ09 ｧ ﾀ ｧ ﾀ ｧ 閨 ｦﾌ ﾀ0506 ｧ0009ｦﾌ0507 ｦﾌ04 05 ｧ ｦﾌ 陦ｧ ﾀ08 TUNEL (Trevigen), 閨0800 ｧ ﾀ01 ｧ ｧ ﾀ ｦﾌ ｦﾌ 08 TUNEL [25]. 6 5 ｧ ｧ 01 ｧ09 06 ｧ ﾀ ｦﾌ00 ﾀｦﾌ09 ｧ ﾀ ｧ00 ｧ ｦﾌ ｧ ｦﾌ04ｦﾌ 陦ｧ05 ｧ ｦﾌ ｦﾌ06 06 ｧ ﾀ ｦﾌ00 ﾀｦﾌ ｦﾌ ｦﾌ06 09 ｧ ｦﾌ04 閨 ｧ ｧ ｧ ｦﾌ ｧ ｧ FITC ｷ ｦﾌ01 ｧ07ｦﾌ00 ｧ06 ｧ ﾀｦﾌ06 ｦﾌ09 06 閨 ｧ06 08 ﾀ ｧ ｧ ﾀ ﾀ ｧ ｧ0606ｦﾌ03 ｧ05 ｧ- ｦﾌ04 05 ｧ ｧ ﾀｦﾌ ﾀｦﾌ 05 ｦﾌ 06 (0,7 % 04 PBS) ｧ 閨06 07ｦﾌ07 ﾀｦﾌ05ｦﾌ 0005 罍 07 09ｦﾌ ｦﾌ0007 ｧ ｦﾌ05ｦﾌ ﾀ ﾀ ｧ 09 ｧ ﾀ00 ｧ ｦﾌ04 05 ｧ, ｧ07 ﾀ0803 ｧ 罍閨 ｧ %-06 09ｦﾌ 閨0605 ｧ 閨06 04 PBS 04 00ｦﾌ05ｦﾌ 陦ｧ ｧ ﾀ06. 6ｦ ｧ05 ｧ ｦﾌ04 05 ｧ 04 0,2 % ｧ07ｦﾌ0706 6ｦ PBS (20 06 ｧ ｦﾌ05ｦﾌ 陦ｧ ｧ ﾀ06). ｮ05 罍閨06, 閨 閨0500 ｦﾌ09 06 閨 ｧ00 08 ｦﾌ FasR, 09 ｦﾌ0106 閨 ｧ05 ｧ 01 ｧ ｧ ｦﾌ 閨 ｧ. 1 7ｦﾌ ﾀ 07 隕ﾌ 09 ｦﾌ0106 閨 罍閨06 07 ｧ07 閨06 ｦﾌ ｧ 04

4 13244 ｯ ｦﾌ07ｦﾌ ｧ 陦. PBS, 09ｦﾌ 閨 ｦﾌ ﾀ08 ｦﾌ ｧ0207ｦﾌ05ｦﾌ 0707 ｧ ｦﾌ04ｦﾌ 陦ｧ05 ｧ 04 PBS, 00ｦﾌ 閨 ｧｦﾌ ｦﾌ ｦﾌ07 ﾀ08 2 % 罍 07 07ｦﾌ00 ｧ05 ｧ ｦﾌ ｧ0207ｦﾌ05ｦﾌ 0707 ｧ PBS (30 06 ﾀ05, ﾀ05/0605), 07 ﾀ ｧ 09ｦﾌ ﾀ ｦﾌ ﾀ05ｦﾌ06 ｧ ｧ07 ﾀ0803 ｧ ｦﾌ04 05 ｧ ｦﾌ ｧ ﾀｦﾌ ｦﾌ ｦﾌ ｧ07 ﾀ ｧ ｧ ﾀ05ｦﾌ ｧ ｧ 0005 罍 07 ｧ07 閨06 ｦﾌ ｧ 00ｦﾌ- 05ｦﾌ 閨 PBS. 1 7ｦﾌ ｧ00 ｧ 05 ｧ03 ﾀｦﾌ ｧ 00 09ｦﾌ ｦﾌ0007 ｧ 0005 罍 07 07ｦﾌ00 ｧ05 ｧ ﾀ05 PBS, 00ｦﾌ 閨 ｦﾌ 0407ｦﾌ ｧ ｧ070605, FITC (1 06 ﾀ05/0605), 07 ﾀ ｧ 09ｦﾌ ﾀ ｦﾌ ﾀ05ｦﾌ06 ｧ ｧ07 ﾀ0803 ｧ ｦﾌ04 05 ｧ ｦﾌ ｦﾌ ｧ00 09ｦﾌ ﾀ ｦﾌ0407ｦﾌ05ｦﾌ ﾀ 罍閨06 ｦﾌ ｧ 04 PBS, 閨0605 ｧ 陦 07 ｧ ｦﾌ04 05 ｧ ｦﾌ0506, ｧ04 05 ｧ, ｦﾌ ﾀ 03 ｧ04 05 ｧ 罔ﾌ 陦ｧ ｦﾌ- 09 ｧ 陦ｧ0606 (1 06 ﾀ05/0605) ｧ 06 ｧ ﾀ ｦﾌ00 ﾀｦﾌ09 ｧ ｦﾌ04 05 ｧ ｧ ｦﾌ ｧ ｧ ｦﾌ ｦﾌ06 09 ｧ ｦﾌ04 閨0500 FITC. 07ｦﾌ0707 ｦﾌ ｧ05 ｧ 0005 罍閨06 00 ｧ0606ｦﾌ03 ｧ05 ｧ ｦﾌ ｧ ﾀ ﾀ 06 ｧ, ﾀｦﾌ07ｦﾌ ｦﾌ ｧ 07 ﾀｦﾌ 0706 ｦﾌ03 03ｦﾌ07 ﾀ06, 07ｦﾌ ｧ ｧ FITC ｦﾌ ｧ ｧ06 ﾀ ﾀ ｧ 09ｦﾌ07ｦﾌ05 09 ｧ ｦﾌ04 05 ｧ, 09ｦﾌ ｧ ｦﾌ ｧ ｧ ｧ ｦﾌ04 05 ｧ 07 ﾀｦﾌ ｦﾌ06ｦﾌ ｦﾌ ImageJ [26] ｧ0007 ｧ ｦﾌ04 05 ｧ ｦﾌ ｧ ﾀ050607ｦﾌ ﾀ 04 ﾀ 07 隕ﾌ 罍閨06 ｧ ｦﾌ09 06 閨 ｧ 隕ﾌ0509 FITC-09ｦﾌ ｧ07 ｧ ﾀ050607ｦﾌ ﾀ. 1 7ｦﾌ ﾀ ｦﾌ ﾀ ｧ ｧ ﾀ - 07 隕ﾌ05ｦﾌ ﾀ ｧ05ｦﾌ 09 ｦﾌ ｧ 0406 閨0607 ｧ 閨070605ｦﾌ ｧ ｦﾌ ｧ ｧ ｦﾌ 閨07ｦﾌ ﾀ ﾀ ｧ 07 隕ﾌ0509 FITC-09ｦﾌ ｧ07 ｧ ﾀ050607ｦﾌ ﾀ 04 ﾀ 07 隕ﾌ 罍閨 ｧ ｧ ﾀ07 ｦﾌ 0607 ｧ07ｦﾌ ( ) ｧ ｧ ｧ ｦﾌ04 05 ｧ ﾀ ｦﾌ0706 ( ) ｧ 05 ｧ03 05 ｧ ﾀｦﾌ ｧ ﾀ05ｦﾌ ｧ ｦﾌ04 05 ｧ ｧ ｦﾌ ｧ ﾀ01 ｧ ｧ ｦﾌ05 ｧ07 ｧ05 02 ﾀ00 ｧ05 ｧ07 1/1 04 隕ﾌ 06 0, ｧ04ｦﾌ0707ｦﾌ05ｦﾌ ｧ 0607 ｧ00 02 ﾀ ﾀ ｧ 0,5 % ｦﾌ 06 ｧ 陦 ｧ 01 ｧ ﾀ07 ｦﾌ 09ｦﾌ ｧ ｦﾌ ｦﾌ ﾀｦﾌ ﾀ ﾀ ﾀｦﾌ0707 ﾀ ｧ07 08; ｧ05ｦﾌ ﾀ07 ｦﾌ 閨 ｧ00 ｧ ｧ ｦﾌ 陦ｧ05 ｧ 09ｦﾌ ﾀｦﾌ0708 ｦﾌ ﾀｦﾌ05ｦﾌ ﾀｦﾌ04 ｧ ｧ ｧ 00 09ｦﾌ06ｦﾌ ﾀ07 ｦﾌ09 ｧ ｧｦﾌ05ｦﾌ05 ｧ ﾀｦﾌ 00 ｧ 罍 ｦﾌ00ｦﾌ ｧ ｧ0009ｦﾌ0507 ｦﾌ04 07 ｧ ｧ 09 ｦﾌ 罍 ｦﾌ NET. ｮ07 ｧ ｧ09 ｦﾌ ﾀ ｧ ｦﾌ ｧ 00 09ｦﾌ06ｦﾌ ﾀ ｦﾌ05ｦﾌ ｧ07 ｧ ｦﾌ05ｦﾌ 03 ｧ ｦﾌ ﾀｦﾌ09ｦﾌ050707ｦﾌ05ｦﾌ 09ｦﾌ07ｦﾌ0007 ｧ ｦﾌ, 閨05 ｧ ｦﾌ ﾀ 00ｦﾌ , 05ｦﾌ05 ｧ0906 ｧ ｧ0407ｦﾌ0007 ｧ ｧ ｦﾌ04 05 ｦﾌ 隕ﾌ 020, ﾀ0706 ｧ ｦﾌ04 05 ｧ ｧ0708 隕ﾌ, 0407ｦﾌ a- ｧb-04ｦﾌ 閨 ｧ 閨 閨070605ｦﾌ ｧ00 ｧ ｦﾌ 隕ﾌ ｦﾌ ｧ ｧ ｦﾌ05 ｧ0906 ｧ ｧ0407ｦﾌ0007 ｧ ﾀ 021,5, 021 ｧ 020,5 00 ｧ ｦﾌ 閨08 07 ｧ06 ｧ 3 06 ｧ ｧ 07 ﾀｦﾌ ｧ ｧ ｧ ｧ ｦﾌ06 陦ｧ 09 ｦﾌ ｧ00 ｧ06ｦﾌ ｧ0708 閨 ｦﾌ07 ｧ ｧ0407ｦﾌ0007 ｧ ﾀ ｧ ｦﾌ 陦ｧ ｦﾌ, 0207ｦﾌ 09ｦﾌ 04ｦﾌ ﾀｦﾌ 06 ﾀ0707ｦﾌ 09 ｦﾌ04ｦﾌ 陦ｧ ｧ ｦﾌ05ｦﾌ ｧ ｧ00 09ｦﾌ 閨0607 ｧ ｦﾌ 隕ﾌ ﾀｦﾌ ｷ30009ｦﾌ0507 ｦﾌ04 05 ｧ 閨 ｧ ｦﾌ 縺 閨0500 ｦﾌ ﾀ ｧ 09ｦﾌ 閨060707ｦﾌ0007 ｧ 閨 ｧ070604ｦﾌ (ds ﾀｦﾌ ) ｧ ｦﾌ0207ｦﾌ 閨0500 ｦﾌ09 06 閨 ｧ00 ｦﾌ 閨07ｦﾌ07 ｧ ｦﾌ (ss ﾀｦﾌ ) ｦﾌ ｦﾌ ｦﾌ09 ｧ ｧ [22]. ｮ ｧ09 ﾀ050607ｦﾌ ﾀ (0,56ﾓ11) 10 6 /0605 PBS ｧ ｧ 00 閨04ｦﾌ 縺 ｦﾌ ｦﾌ06 1 %-05ｦﾌ ｦﾌ ﾀｦﾌ ﾀｦﾌ 05 ｦﾌ 06 IV 07 ｧ09 (Sigma, ｮ0ｹ01 7), 07 07ｦﾌ00 ｧ05 ｧ 閨 ｦﾌ ﾀ05ｦﾌ ｧ 閨06 07ｦﾌ07 ﾀｦﾌ05ｦﾌ 0005 罍 18 ﾁ ｦﾌ ｧ 罍 09ｦﾌ ｧ ｧ ｧ ｧ ｦﾌ, 00ｦﾌ 閨 ｧ 2,5 M NaCl, EDTA, Tris-HCl, 1 % ｧ0500 ﾀｦﾌ ｧ07 07 ｧ 0, / ｦﾌ0706 ｧ , 1 7 8,0, ｮ ﾀ07 ｦﾌ09ｦﾌ ｦﾌ04ｦﾌ 陦ｧ05 ｧ 04 ｯ1 7 ｭ ,3 (ds ) ｧ05 ｧ ｦﾌ 06 0,3 03 NaOH, EDTA ｧ 1 % DMSO (ss ) ｧ ｧ07 09 ｧ 0,56 6 5/0006. ｮ05 罍閨06 ｦﾌ09ｦﾌ05 00 ﾀ ｧ04 05 ｧ 04 0,4 03 Tris-HCl, ph 7,4, 04 PBS, ｧ04 05 ｧ 07 04ｦﾌ 閨080006, 閨0605 ｧ 陦 07 ｧ- ｦﾌ04 05 ｧ ｦﾌ05ｦﾌ06 ｧ 09ｦﾌ ｦﾌ ﾀ 03 ｧ04 07 ｧ00 Sybr-Green 06 ｧ ﾀ ｦﾌ00 ﾀｦﾌ09 ｧ ｦﾌ04 05 ｧ 04ｦﾌ ｦﾌ ｦﾌ ｧ ｷ3 ｦﾌ ｧ00 ﾀｦﾌ ｦﾌ ｧ 09ｦﾌ 09 ｦﾌ CASP [27]. 1 7ｦﾌ ﾀ ｦﾌ 閨060707ｦﾌ0007 ｧ ｧ05 06ｦﾌ ｦﾌ0007 ﾀｦﾌ mt (Olive tail moment).

5 130ｷ 隕ﾌ04 07 ｧ ｧ0407ｦﾌ05ｦﾌ ｦﾌ ﾀ ｧ ｦﾌ ｧ06 09 ｦﾌ07ｦﾌ07 06 ｧ ｮ07 07 ｧ0007 ｧ ﾀ 閨 閨 ｧ ｧ00 ｧ ﾀ ｧ ｦﾌ 閨06 ｦﾌ ｦﾌ 閨 ﾀｦﾌ0707 ｦﾌ ｧ ｦﾌ ｧ04ｦﾌ ｧ02 ｧ 閨08 09ｦﾌ ﾀ ｧ ﾀｦﾌ0707 ｦﾌ ｧ ｦﾌ ｧ ｧ ｦﾌ04 05 ｧ ｦﾌ06ｦﾌ ｧ ﾀｦﾌ ｧ0007 ｧ ﾀ ｧ 07ｦﾌ0506ｦﾌ05ｦﾌ ｦﾌ04 02 ｮ06 ｧ 07ｦﾌ04 00ｦﾌ ｧ ﾀ ｧ 閨 ｧ 09ｦﾌ ﾀ ( ｧ ｦﾌ05 ｧ0007ｦﾌ- ｧ 01 ｧ07ｦﾌ00 ｧ06 ｧ00, ﾀｦﾌ ). ｮ 06 閨07 ｧ06 09ｦﾌ ﾀ ｧ ｧ04 05 ｧ ｧ0009ｦﾌ0507 ｦﾌ04 07 ｧ ｦﾌ STATISTICA ｭ6ｦ0 ｰ6ｧ804 ｯ1 7 ｯ6ｧ 陦ｧｦﾌ080007ｦﾌ 縺02 ｧ04ｦﾌ ﾀ ｧ 0505 in vivo. 1 7 陦ｧｦﾌ080007ｦﾌ 縺02 ｧ04ｦﾌ ﾀ ｧ ｦﾌ 閨0606ｦﾌ ｧ ｦﾌ ｧ00. 1, : ｦﾌ ｧ ﾀ ｧ 0800 ﾀｦﾌ ｧ 09 ｦﾌ07ｦﾌ07 06 ｧ 04 隕ﾌ ｧ ｧ ｧ ﾀ ｦﾌ ﾀ ｧ. 1 7 閨07 ﾀｦﾌ 04 ｦﾌ ﾀ ﾀ 00 09ｦﾌ 06 ｧ , ﾀｦﾌ07ｦﾌ ｦﾌ0507ｦﾌ ｧ ( ｧ00. 1, 03). 1 7 ｧ ｦﾌ 09ｦﾌ05ｦﾌ05 ｧ ﾀ ｧ ｧ 09ｦﾌ 閨0607 ｧ ﾀ06 09ｦﾌ ｦﾌ ｧ ﾀｦﾌ ｧ 09 ｦﾌ- 07ｦﾌ07 06 ｧ 04 隕ﾌ ｧ ) 03 ｧ ﾀ ｦﾌ09ｦﾌ07ｦﾌ05 09 ｧ ｧ ｦﾌ ﾀ ｧ ｧ ｦﾌ ﾀ 09ｦﾌ ｦﾌ 閨06 縺 ｧ00; 03) 陦ｧ07 06 ｧ ﾀ ｧ ｧ ｦﾌ 閨07ｦﾌ07 ｧ (1) ｧ 閨 ｧ (2) 0604ｦﾌ ﾀ06 in vivo ﾀ 0905 ｧ ｧ ｦﾌ ｦﾌ ｧ00 04 隕ﾌ ｰ ｧ ｧ06 ﾁ ｧ 閨09ｦﾌ ﾀｦﾌ 閨 ｦﾌ05ｦﾌ 04ｦﾌ ｦﾌ ｧ00 ﾀ050607ｦﾌ ﾀ ｧ 09ｦﾌ 閨 ｦﾌ 00ｦﾌ ｧ00 ｧ ﾀ01 ｧｦﾌ ｦﾌ ﾀ07 ｧ0407ｦﾌ0007 ｧ ﾀ07 ｧ ｧ ｧ 04 ﾀ ﾀ 00, ｦﾌ 隕ﾌ ( ｧ00. 2, ). 1 7 閨07 ﾀｦﾌ ｦﾌ ﾀ 00 隕ﾌ ｦﾌ 09ｦﾌ05ｦﾌ05 ｧ ﾀ ｧ06 ｧ ｧ ﾀ ｧ 05 ｧ ｦﾌ07ｦﾌ ｦﾌ ﾀ ｦﾌ ﾀ ( ｧ00. 2, 03). ｮ08 閨00 09ｦﾌ ｧ02 ｧ ｧ ｦﾌ 閨06, 03ｦﾌ ﾀ050607ｦﾌ ﾀ 05 ｧ ｦﾌ ｧ ｦﾌ0907ｦﾌ. ｯ ﾀ ｧ06 ｦﾌ03 ｦﾌ06, ｧ ｦﾌ0300ｦﾌ 陦ｧ06ｦﾌ, 07ｦﾌ 0706 隕ﾌ ｦﾌ0207ｦﾌ 閨09ｦﾌ ﾀｦﾌ ｧ04 07 ｧ00 ﾀ050607ｦﾌ ﾀ 04 ｦﾌ ｦﾌ ﾀ ｧ0706 縺 ﾀ0706 隕ﾌ ｦﾌ04ｦﾌ 04 ｧ00 ｧ06ｦﾌ0007 ｧ ｦﾌ ﾀ ｧ 07 ｦﾌ ｧ06 ｧ ﾀ07 ｧ ｧ ｧ ｧ ﾀ ｦﾌ00ｦﾌ0307ｦﾌ ﾀ ｧ 0505 ﾀ 04ｦﾌ ｦﾌ ｧ09.

6 13246 ｯ ｦﾌ07ｦﾌ ｧ 陦. 1 7 ｧ ｦﾌ 09ｦﾌ05ｦﾌ05 ｧ ﾀ ｧ 0505, 05 ｧ ｦﾌ07ｦﾌ ｦﾌ ｦﾌ ﾀ06 ｧ ｧ ﾀ in vivo 09ｦﾌ ｦﾌ ｧ00 09 ｦﾌ07ｦﾌ07 06 ｧ 04 隕ﾌ ) 1 7 ﾀｦﾌ ｧ06 ｧ ｧ00 ｦﾌ 閨07ｦﾌ07 ｧ ｦﾌ ﾀ06 09ｦﾌ ｦﾌ ｧ00; 03) 06ｦﾌ 09ｦﾌ05ｦﾌ05 ｧ ﾀ ｧ06 ｧ ｧ ﾀ06 ｧ 05 ｧ ｦﾌ07ｦﾌ ｦﾌ ｦﾌ ﾀ06; 04) 09 ｧ ﾀ07ｦﾌ ｧ ｧ00 00 閨06 09ｦﾌ07ｦﾌ ｦﾌ ｦﾌ04 04 ｦﾌ ｦﾌ ﾀ06. ｰ ｧ ｧ06 ﾁ ｦﾌ ｦﾌ ｧ ﾀ ｧ ｦﾌ 閨06 縺 ｧ ｧ0507 ｧ07 ｦﾌ ｦﾌ06ｦﾌ ｧ ﾀ ﾀ01 ｧ ｧ, 0000ｦﾌ 閨 ﾀｦﾌ ｧ 09ｦﾌ 閨06 縺 ｧ00 09 ｦﾌ07ｦﾌ07ｦﾌ04: ｧ 縺 ﾀ ｧ00 ｧ06ｦﾌ0007 ｧ 06ｦﾌ 09ｦﾌ05ｦﾌ05 ｧ ﾀ ｧ00 ｧ ｧ ﾀ ｧ ｦﾌ07 隕ﾌ 06 ( ｧ00. 3, ) ｧ ﾀ07 ｧ ｧ09 04ｦﾌ 07 ｧ ﾀ 0904 ｧ ｦﾌ ( ｧ00. 3, 03). ｨC ｧ07ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀ 00 隕ﾌ / ﾀ ｦﾌ 閨0607 ｧ 閨 ﾀ01 ｧ09 00 閨06 07ｦﾌ05ｦﾌ 0005ｦﾌ00 ｧ ｦﾌ04 09ｦﾌ07ｦﾌ ｦﾌ ﾀ050607ｦﾌ ﾀ ｧ 0706ｦﾌ03 07 ｧ ﾀ01 ｧｦﾌ ｦﾌ ﾀ07 ｧ0407ｦﾌ0007 ｧ ﾀ ｧ ( ｧ00. 3, 04, 05). 6 7ｦﾌ / ﾀ05, ﾀ ﾀ 04 ｧ 閨07ｦﾌ, ｧ07ｦﾌ07ｦﾌ ﾀ00 ｧ0207ｦﾌ ｦﾌ ｦﾌ ｦﾌ 隕ﾌ ｦﾌ 隕ﾌ0507 ｧ ｦﾌ06, 07ｦﾌ ｦﾌ03 07 ｧ- 06ｦﾌ06 09ｦﾌ07 ｧ ｧ ｧ0708 閨 ( ｧ00. 3, 05), 05ｦﾌ04ｦﾌ ｦﾌ 04ｦﾌ ｦﾌ ｧ ｧ ﾀ01 ｧｦﾌ ｦﾌ ﾀ07 ｧ0407ｦﾌ0007 ｧ ﾀ ｧ ｦﾌ 閨06 縺 ｧ ｧ ｦﾌ ﾀ ｧ ｧ ﾀ050607ｦﾌ ﾀ ｮ ｦﾌ ｦﾌ00 ﾀｦﾌ0507 ﾀ ｦﾌ0907ｦﾌ07 ｧ ﾀ ｧ ｦﾌ07ｦﾌ ｦﾌ ﾀ050607ｦﾌ ﾀ, 04 ﾀ ｧ07 陦ｧ ﾀ 07ｦﾌ 01 ｧ07ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀｦﾌ05ｦﾌ 閨06 縺 ｧ ｧ0009ｦﾌ0507 ｦﾌ04 05 ｧ 08 ﾀ ｧ09 ﾀ07 ｧ04 ｧ- ｦﾌ ｦﾌ ﾀ ﾀ ﾀ ﾀ ｧ 0505, ｦﾌ09 06 閨 ｦﾌ ｧ ｦﾌ01 ｧ07ｦﾌ00 ｧ06 ｧ ﾀ ｧ 09ｦﾌ ｦﾌ ｧ ｧ ﾀ ｧ09 ｧ ｧ , 閨 ｧ00. 4, 09ｦﾌ- ﾀ , 0207ｦﾌ 01 ｧ07ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀ ｧ ﾀ07 ｦﾌ07 ｦﾌ 閨07ｦﾌ ﾀ 0707ｦﾌ05ｦﾌ 閨0607 ｧ 隕ﾌ / ﾀ05 03ｦﾌ , ｦﾌ07 09ｦﾌ 隕ﾌ ｦﾌ05ｦﾌ 閨0607 ｧ ｧ / ﾀ05.

7 130ｷ 隕ﾌ04 07 ｧ ｧ0407ｦﾌ05ｦﾌ ｦﾌ ﾀ ｧ ｦﾌ ｧ06 09 ｦﾌ07ｦﾌ07 06 ｧ ｧ ﾀ ｧ ｦﾌ 閨07ｦﾌ ﾀ 0707ｦﾌ 閨0607 ｧ ｧ0507 ｧ07 ｦﾌ ｦﾌ06ｦﾌ ｧ0706. ) 03 ｧ ﾀ ｦﾌ09ｦﾌ07ｦﾌ ｧ ｧ ｦﾌ ﾀ ｧ 09ｦﾌ ｦﾌ 閨06 縺 ｧ 隕ﾌ / ﾀ05; 03) ｦﾌ 閨07ｦﾌ 閨 ｧ00 00 閨06 07ｦﾌ05ｦﾌ 0005ｦﾌ00 09ｦﾌ07ｦﾌ ｦﾌ ｦﾌ04 ｧ ｧ00 ｦﾌ 閨07ｦﾌ07 ｧ ｦﾌ ｦﾌ ｦﾌ 閨06 縺 ｧ00 隕ﾌ / ﾀ05; 04) ｦﾌ ﾀ07 ｦﾌ 0607 ｧ07ｦﾌ 閨0607 ｧ 隕ﾌ ｧ / ﾀ05; 05) ﾀ01 ｧｦﾌ ｦﾌ06 04ｦﾌ ｦﾌ ｧ ﾀ ｧ 09ｦﾌ 閨0607 ｧ 隕ﾌ / ﾀ05 ｧ 0706ｦﾌ03 07 ｧ ﾀ01 ｧｦﾌ ｦﾌ ﾀ07 ｧ0407ｦﾌ0007 ｧ ﾀ ｧ 09ｦﾌ 隕ﾌ / ﾀ05. ｰ ｧ ｧ06 ﾁ200 C ｦﾌ 閨0607 ｧ , ﾀｦﾌ ｧ , 閨04 07 閨06 09ｦﾌ / ﾀ ｦﾌ 陦ｧ05 ｧ 09 ｦﾌ05 ｧ ｧ ﾀ06 BrUdR ｧ 閨 ｧ09 ｧ ﾀ 01 ｧ ｧ 0505 ｧ ﾀ050607ｦﾌ ﾀ ﾀ ( ). 6 5 ﾀ ｧ0403 ｧ 縺 ﾀ06 09 ｦﾌ ｧ 00 09ｦﾌ06ｦﾌ FITC- ﾀｦﾌ ｧBrUdR 0707 ｧ ｦﾌ ｦﾌ0207ｦﾌ ｦﾌ03 03ｦﾌ07 ﾀ ｧ ｧ 0706 縺07 05 ｧ-

8 13248 ｯ ｦﾌ07ｦﾌ ｧ 陦. ｯ 0305 ｧ01 1. ｮ ﾀ ｧ ｦﾌ 0907 ｧ ﾀ ﾀ , ｦﾌ 閨06 縺 ｧ BrUdR 6 7ｦﾌ, 0605/ ﾀ ｦﾌ 閨06 縺 ｧ BrUdR 6 7ｦﾌ, 0605/ ﾀ ｦﾌ 閨06 縺 ｧ BrUdR 6 7ｦﾌ, 0605/ ﾀ ｧ ｧ ｧ ｧ ﾀ ｧ00 ﾀ07 ｧ0407ｦﾌ ﾀ ﾀ ﾀ ﾀ ｧ ｦﾌ ｦﾌ 閨07ｦﾌ ﾀ ( / ﾀ05) ｧ 閨0408 ﾀ ( / ﾀ05) ｧ ﾀ01 ｧ ｧ ｰ ｦﾌ ﾀ ｦﾌ09 06 閨 ﾀ ﾀ 08 閨 ｧ ｧ0407ｦﾌ FITC ｦﾌ ｧ ｧ ﾀ050607ｦﾌ ﾀ. ｰ ｧ ｧ06 ﾁ ｧ ｧ ｧ 01 ｧ00 ﾀ050607ｦﾌ ﾀ ﾀ ｧ 0505 ( ) ｧ ｧ00 ｦﾌ ｦﾌ 閨07ｦﾌ ﾀ ( / ﾀ05) ｧ 閨0408 ﾀ ( / ﾀ05) ｧ ﾀ- 01 ｧ ｧ (03) 01 ｧ ｧ ｦﾌ 閨 ｦﾌ ﾀ0506 ( ｧ00. 5, ) ｧ 09ｦﾌ 閨0002 ｧ ｧ 02 ｧ0005ｦﾌ FITC-09ｦﾌ ﾀ0800ｦﾌ 陦ｧ07 ｧ ｦﾌ04 閨 ｦﾌ04 ( ｧ00. 5, 03). ｮ 06 閨 ｧ0005ｦﾌ 09ｦﾌ ﾀ0800ｦﾌ , 09 ｧ00ｦﾌ 閨 陦ｧ07 ｧ ｦﾌ04 陦ｧ 00 06, 閨 ｧ 07ｦﾌ02 ﾀｦﾌ ｧ ｦﾌ ﾀ 07 隕ﾌ 06 ｧ ﾀ ｦﾌ09ｦﾌ07ｦﾌ05 09 ｧ ｧ 閨07ｦﾌ, 0207ｦﾌ 04 ｦﾌ 閨0607 ｧ06 01 ｧ07ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀｦﾌ 隕ﾌ ｦﾌ ｧ0005ｦﾌ

9 130ｷ 隕ﾌ04 07 ｧ ｧ0407ｦﾌ05ｦﾌ ｦﾌ ﾀ ｧ ｦﾌ ｧ06 09 ｦﾌ07ｦﾌ07 06 ｧ 249 FITC-09ｦﾌ ﾀ0800ｦﾌ ｦﾌ 隕ﾌ ｦﾌ 閨0607 ｧ06 17 ｧ / ﾀ ｦﾌ ｧ ｦﾌ ｧ ｧ06 02 ｧ ｦﾌ ﾀ0800ｦﾌ04 09ｦﾌ ｧ ﾀ07ｦﾌ06 ｦﾌ07 ｦﾌ 閨07ｦﾌ 隕ﾌ / ﾀ05, 00ｦﾌ ｦﾌ 隕ﾌ0007ｦﾌ ｦﾌ0007 ｧ 0007 ｧ ｧ ｦﾌ ﾀ, p =0, ｧ ｧ ﾀ07 09 ｦﾌ07ｦﾌ0707ｦﾌ05ｦﾌ ｧ ｧ00 04 隕ﾌ ｮ ｦﾌ ｯ 0305 ｧ01 2. ｮ ﾀ ｧ ｦﾌ 0907 ｧ ﾀ0708 ｦﾌ ｧ ﾀ , ｦﾌ 閨06 縺 ｧ ｦﾌ07ｦﾌ ｦﾌ / ﾀ ｧ ｦﾌ 閨06 縺 ｧ ｦﾌ, 0605/ ﾀ ｧ ｦﾌ 閨06 縺 ｧ ｦﾌ07ｦﾌ ｦﾌ, ｧ ｧ TUNEL- 閨 ﾀ01 ｧ00 09ｦﾌ0907ｦﾌ ｦﾌ06 00 閨06 07ｦﾌ ｦﾌ ﾀ ｧ ｧ0707 ﾀ (07), 09ｦﾌ 閨0607 ｧ /0605 ( ) ｧ 09ｦﾌ ｦﾌ ｧ00 09 ｦﾌ07ｦﾌ07 06 ｧ ｦﾌ 閨 ｧ ﾀ01 ｧ / ﾀ05 ( ). 1 7 ｧ0406 閨 ｧ ｧ ﾀ ｦﾌ09ｦﾌ07ｦﾌ05 09 ｧ ｧ ｦﾌ ﾀ ｧ. ｯｦﾌ02 ﾀ ｧ ﾀ ｦﾌ 06 ｧ ｦﾌ ｦﾌ06 09ｦﾌ 0905ｦﾌ04 陦ｧ 閨 ｦﾌ ｧ ｦﾌ ｧ ｧ ｦﾌ05ｦﾌ 00 閨06 07ｦﾌ05ｦﾌ 0005ｦﾌ ﾀ ｧ 04 09ｦﾌ ｧ00 06 ｧ ﾀ ｦﾌ00 ﾀｦﾌ09. ｰ ｧ ｧ06 ﾁ200

10 13250 ｯ ｦﾌ07ｦﾌ ｧ 陦. 1 7ｦﾌ ｧ ﾀ01 ｧ ｧ ( / ﾀ05) ﾀ ﾀ 0905 ｧ ｦﾌ ｦﾌ06 02 ｧ0005ｦﾌ 09ｦﾌ05 ｧ0303 ｧ00 TUNEL-09ｦﾌ ｧ07 ｧ ﾀ050607ｦﾌ ﾀ (09ｦﾌ07ｦﾌ 07 ｧ00. 6). 1 7ｦﾌ05 ｧ0303 ｧ06 ﾀ ﾀ ｧ 05ｦﾌ ﾀ 05 ｧ ｦﾌ06 00 閨06 07ｦﾌ ｦﾌ ﾀ ｧ ｦﾌ06 ｧ ﾀ06 ｧ ｦﾌ 09 ｦﾌ ImageJ ｧ ｧ0407ｦﾌ0007 ｧ ｦﾌ ｧ ｧ, 閨 ｦﾌ ｦﾌ 閨07ｦﾌ , 閨 ｧ 閨06 07ｦﾌ02 ﾀ ｧ ｦﾌ ﾀ 07 隕ﾌ 06 ｧ ﾀ ｦﾌ09ｦﾌ07ｦﾌ05 09 ｧ06. ｮ 06 閨07 ｧ ｧ00 閨0500 ﾀ 07 隕ﾌ ｦﾌ0206 ﾀ ｦﾌ03ｦﾌ ｧ ﾀ06 07 ｧ ｧ 05ｦﾌ ｧ ｦﾌ ｧ 0307 ｧ00 06 ｧ ｧ 隕ﾌ ｧ04ｦﾌ 陦ｧ07 ﾀ 00 ﾀｦﾌ0507 ﾀｦﾌ-07 ｧ0308 閨 ｧ- 06ｦﾌ ｧ ｧ09 02 ｧ ｦﾌ05 ｧ0303 ｧ00 ﾀ050607ｦﾌ ﾀ ﾀ ( ｧ04ｦﾌ 閨 ). 1 7 閨07 ﾀｦﾌ 閨04 ｧ ｦﾌ06 ｦﾌ ｧ ｦﾌ 隕ﾌ ｧ04ｦﾌ 陦ｧ07 ﾀ 隕ﾌ0007ｦﾌ ｦﾌ ｧ ｧ09 01 ｧ07ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀｦﾌ05ｦﾌ 閨06 縺 ｧ 陦ｧ 01 ｧｦﾌ0707ｦﾌ ﾀｦﾌ07 陦ｧ01 ｧｦﾌ07 ｧ ｦﾌ ﾀ08 (p <0,001). 1 7 ｧ 閨 ｦﾌ ﾀ ｧ 閨 ｧ ｦﾌ ｦﾌ ｦﾌ 閨06 縺 ｧ 陦ｧ 01 ｧｦﾌ0707ｦﾌ ﾀｦﾌ07 陦ｧ01 ｧｦﾌ07 ｧ ｦﾌ ﾀ ｧ ｧ0007 ｧ06 09 ｦﾌ07ｦﾌ0707ｦﾌ05ｦﾌ ﾀｦﾌ07 陦ｧ01 ｧｦﾌ07 ｧ ｦﾌ04 07 ｧ00 (1 06 ) ｧ07 閨0801 ｧ ｦﾌ 閨 ｧ ﾀ ｦﾌ ｦﾌ ｧ00. ) ｧ ds ﾀｦﾌ ｧ ﾀ050607ｦﾌ ﾀ ｧ0707 ﾀ0707ｦﾌ ﾀ ｧ, ｦﾌ03 03ｦﾌ ｦﾌ ｧ ( )-ｦﾌ03 03ｦﾌ ｦﾌ ﾀ ｧ; 03) 05 ｧ0007ｦﾌ 閨 ｧ00 ﾀｦﾌ ｦﾌ ｧ 閨 ｧ ｧ 閨 ﾀ050607ｦﾌ ﾀ; 04) 閨07 ｧ06 ｦﾌ0707ｦﾌ00 ｧ ｧ00 ds- 閨 ｧ ｧ , ｧ ｧ 00ｦﾌｦﾌ ｧ 閨 ｧ (03). ｰ ｧ ｧ06 ﾁ400

11 130ｷ 隕ﾌ04 07 ｧ ｧ0407ｦﾌ05ｦﾌ ｦﾌ ﾀ ｧ ｦﾌ ｧ06 09 ｦﾌ07ｦﾌ07 06 ｧ ﾀ 04 ｧ 閨07ｦﾌ, ﾀｦﾌ07 陦ｧ01 ｧｦﾌ07 ｧ ｦﾌ04 07 ｧ ｧ ｦﾌ 06 ｧ ｦﾌ04 07 ｧ06 閨 ｧ ｦﾌ ｦﾌ 09 ｦﾌ ｧ ｧ ﾀ ｦﾌ09ｦﾌ07ｦﾌ05 09 ｧ0000 ﾀｦﾌ ( ｧ00. 7, ), ｧ0007ｦﾌ 閨 ｧ ﾀｦﾌ ｦﾌ ｧ 09ｦﾌ 閨0607 ｧ ( ｧ00. 7, 03) ｧ 00ｦﾌｦﾌ 閨07 ｧ06 08 ｦﾌ ｦﾌ 閨0607 ｧ , ｧ ｧ 0807 ｧ 閨 ｧ ( ｧ00. 7, 04). ｯ ﾀ ｧ06 ｦﾌ03 ｦﾌ06, ｦﾌ ｦﾌ ﾀ06 ﾀ ﾀ ｧ 09ｦﾌ0907ｦﾌ, 07 ﾀ ｧ ﾀｦﾌ05 ｧ 閨 ｧ ｦﾌ ｦﾌ 閨 ｧ ｧ ﾀ ﾀ ｦﾌ07ｦﾌ0707ｦﾌ05ｦﾌ ｧ ｧ00 04 隕ﾌ ｮ ｰ ｭ1 70ｷ3 ｭ ｦﾌ ﾀ ｧ ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀ ｧ 09ｦﾌ ｦﾌ ﾀ ｧ 0505, ﾀ ﾀ ｧ ｧ0706 縺 ｧ00 ｧ06ｦﾌ ｧ07ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀｦﾌ05ｦﾌ ﾀ07 ｦﾌ07 隕ﾌ ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀ ﾀ ｦﾌ00ｦﾌ0307ｦﾌ ﾀ ｧ ﾀ 04ｦﾌ ｦﾌ ｧ09 ｦﾌ07 09ｦﾌ 閨0607 ｧ [28, 29]. ｮ ｦﾌ 閨07ｦﾌ 0007ｦﾌ ｦﾌ0706, 0706ｦﾌ0300ｦﾌ 陦ｧ06ｦﾌ 閨09ｦﾌ ﾀｦﾌ ﾀ 0807ｦﾌ ｧ ｧ ( ｧ00. 1), 00 陦 0805ｦﾌ 0007ｦﾌ ｦﾌ0706, ｧ00 ｦﾌ ﾀ 隕ﾌ ｦﾌ0207ｦﾌ 閨0500 ﾀ050607ｦﾌ0207ｦﾌ05ｦﾌ ｧ ﾀ01 ｧｦﾌ ｦﾌ05ｦﾌ 04ｦﾌ ｦﾌ ｧ ﾀ ｧ 0505 ( ｧ00. 2 ｧ 3) ｦﾌ ﾀ 05 ｧ, 0207ｦﾌ 閨04 ｧ ｦﾌ 閨0607 ｧ ｧ07ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀｦﾌ 隕ﾌ 閨 ﾀ ｦﾌ ｦﾌ ｦﾌ ﾀ 09ｦﾌ 閨 ｧ07ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀｦﾌ0608 閨06 縺 ｧ ｦﾌ 09ｦﾌ ﾀ ( ﾀｦﾌ07 陦ｧ01 ｧｦﾌ07 ｧ ｦﾌ04 07 ｧ ﾀ ｧ) [30]. 6ｦ0 閨060007, ｧ0009ｦﾌ ｦﾌ ( ), ｦﾌ ﾀ 05 ｧ, 0207ｦﾌ 07ｦﾌ ｦﾌ ﾀ ｧ 09ｦﾌ ﾀｦﾌ07 陦ｧ01 ｧｦﾌ07 ｧ ｦﾌ04 07 ｧ ｦﾌ01 ｧ ｧ ｦﾌ ｦﾌ07 ｧ ｧ ｦﾌ ﾀ ｧ ｧ ﾀ ﾀ06 ( ｧ00. 5) , 09 ｦﾌ 09ｦﾌ0907ｦﾌ07 ｧ ﾀ ﾀ07ｦﾌ ﾀ 0009, ﾀ050607ｦﾌ , 0800 ﾀｦﾌ ｦﾌ0907ｦﾌ07 ｧ ﾀ ｧ ﾀ ﾀ ｧ. ｮ07 ｧ ｧ ﾀ ｧ ｧ ｦﾌ ｧ ｧ ｦﾌ000707ｦﾌ0007 ｧ ﾀ050607ｦﾌ0207ｦﾌ 05 ｧ ｧ ﾀ050607ｦﾌ ﾀｦﾌ0609ｦﾌ ｦﾌ ﾀ ｧ ｧ ﾀ ﾀ ｧ (060703) ｧ ﾀ ﾀ ｧ ｦﾌ ｦﾌ 閨07 ｧ 陦ｧ 罍 ｦﾌ ｧ ｧ 閨 ｧ ﾀ 06 ｧ 0706 罍 ｦﾌ07ｦﾌ04 [31] ｦﾌ07 ｧ ﾀ07 ｧ0407ｦﾌ 09 ｦﾌ05 ｧ0906 ｧ ｦﾌ ｦﾌ 閨0607 ｧ06 ｧ 06ｦﾌ ﾀ ｧ ｦﾌ 罍 ｦﾌ ﾀ06 06 [32], 09ｦﾌ 閨 ｦﾌ ｦﾌ00ｦﾌ0307ｦﾌ ﾀ 0706 罍 ｦﾌ ｷ30009ｦﾌ ﾀ ｦﾌ- 05 ｧ ｧ0407ｦﾌ05ｦﾌ 06 ﾀ06 03 ｦﾌ06 閨06 ｦﾌ ﾀ00 ｧ08 ｧ 陦ｧ07, BrUdR, ｧ ｧ ｧ ｦﾌ04 05 ｧ ﾀ ｦﾌ ｧ ﾀ01 ｧ ｧ ( ) ｦﾌ ﾀ 05 ｧ, 0207ｦﾌ 04 ｦﾌ ｧ07 閨0801 ｧ ｦﾌ ｦﾌ06 09ｦﾌ 閨0607 ｧ06 04ｦﾌ ｦﾌ05 ｧ ｧ ﾀｦﾌ07 陦ｧ01 ｧｦﾌ07 ｧ ｦﾌ ｦﾌ ﾀ ｦﾌ 04ｦﾌ ｧ , 0207ｦﾌ, ﾀ ﾀ ｦﾌ , 00ｦﾌｦﾌ ｧ ｦﾌ 閨060707ｦﾌ0007 ｧ 09ｦﾌ ｧ ｦﾌ 閨060707ｦﾌ ﾀｦﾌ07 陦ｧ01 ｧｦﾌ07 ｧ ｦﾌ ｦﾌ ﾀ ｧ ( ｧ00. 5) ｦﾌ ﾀ ｦﾌ 閨 ｦﾌ- 00ｦﾌ0307ｦﾌ ｦﾌ ﾀ ｧ 0505 ﾀ 04ｦﾌ ｦﾌ ｧ09 09ｦﾌ ｦﾌ 閨06 縺 ｧ , 閨 ｧ00. 1 ｧ 2, 05ｦﾌ04ｦﾌ 0007 ｦﾌ 07ｦﾌ06, 0207ｦﾌ ｦﾌ ﾀ ｧ ｧ ﾀ0706 ｧ0007 ｧ ﾀ ｧ, 0000ｦﾌ 閨 ﾀｦﾌ ｧ 04 ｦﾌ ｧ ｧ00: ｧ0706 縺07ｦﾌ ｧ00 ｧ06ｦﾌ ｧ ｦﾌ07 隕ﾌ 06/07 05 ｧ02 ｧ06 09ｦﾌ ｦﾌ05 01 ｧ07ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀｦﾌ05ｦﾌ 閨06 縺 ｧ00, ﾀ07 ｧ04 01 ｧ ｧ ｧ 06ｦﾌ04, 09ｦﾌ0907ｦﾌ 09ｦﾌ07ｦﾌ ｦﾌ ﾀ050607ｦﾌ ﾀ. 6ｧ8ｦﾌ05 ｧ0207ｦﾌ 閨09ｦﾌ , 0207ｦﾌ ﾀ 0505 ｦﾌ ﾀ ｦﾌ00ｦﾌ0307ｦﾌ ﾀ 04ｦﾌ ｦﾌ ｧ09 ｧ 09ｦﾌ 陦ｧ 01 ｧｦﾌ0707ｦﾌ05ｦﾌ 04ｦﾌ 閨06 縺 ｧ00. 0ｷ 隕ﾌ04 07 ｧ06, 07 05ｦﾌ05 ｧ0207ｦﾌ 閨06 閨 , 04 ﾀｦﾌ07ｦﾌ ｦﾌ06 04 ﾀ ｧ ｦﾌ 04ｦﾌ 閨 ｧ ｧ0009ｦﾌ0507 ｦﾌ04 05 ｧ ｦﾌ ｧ06 09 ｦﾌ07ｦﾌ07 06 ｧ 05ｦﾌ05ｦﾌ ｧ04ｦﾌ 隕ﾌ ( ), 09ｦﾌ 閨 陦ｧ05ｦﾌ 0807ｦﾌ 閨09ｦﾌ05ｦﾌ ｧ06. TUNEL ｦﾌ ｧ ｦﾌ05ｦﾌ 00 閨06 07ｦﾌ05ｦﾌ 0005ｦﾌ00 ( 09ｦﾌ- 0907ｦﾌ 09ｦﾌ07ｦﾌ ｦﾌ ﾀ050607ｦﾌ ﾀ) 陦ｧ 01 ｧｦﾌ0707ｦﾌ ﾀｦﾌ07 陦ｧ01 ｧｦﾌ07 ｧ ｦﾌ ｦﾌ ﾀ ｧ 隕ﾌ0007ｦﾌ ｦﾌ 07 ｧ ﾀｦﾌ04ｦﾌ ｦﾌ ｦﾌ ﾀ ｧ ( ｧ00. 6) ｦﾌ ｧ ｧ ｦﾌ0706

12 13252 ｯ ｦﾌ07ｦﾌ ｧ 陦. 09ｦﾌ0907ｦﾌ, ﾀ ﾀ 09ｦﾌ ﾀ 07ｦﾌ 07 ｧ00. 7, ﾀｦﾌ 0605 ｧ ｦﾌ 0007 ｧ ｧ0606 ﾀｦﾌ05 ｧ 閨 ｧ ｦﾌ ﾀ ﾀ ﾀ ｧ, ﾀｦﾌ07ｦﾌ ﾀ06 06 ｧ 09ｦﾌ0907ｦﾌ07 ｧ ﾀｦﾌ 閨 ｧ ｧ [33]. ｮ 閨08 09ｦﾌ 06 ｧ ｦﾌ04 07 ｧ0606 閨 ｧ ｦﾌ04 (6 71 7) ｧ 09ｦﾌ0907ｦﾌ ｦﾌ06 ｦﾌ ｧ ｧ 09ｦﾌ ﾀ 07 04ｦﾌ 0607ｦﾌ05 ｧ00 ｧ 隕ﾌ04 07 ｧ0000 [34]. 0ｷ 陦ｧ04 ｧ ｦﾌ, 0207ｦﾌ 0007 ｧ ｧ06 09ｦﾌ0907ｦﾌ07 ｧ ﾀｦﾌ 05 ｧ ｧ 09ｦﾌ07ｦﾌ ｦﾌ ﾀ050607ｦﾌ ﾀ ﾀ ｧ 0505 ﾀｦﾌ 0605 ｧ ｦﾌ 0007 ｧ ｧ0606 ﾀｦﾌ05 ｧ ｧ 閨07 ﾀｦﾌ 04ｦﾌ 07 ｧ ﾀ ｦﾌ09 ｦﾌ00, 09ｦﾌ ﾀｦﾌ07 陦ｧ01 ｧｦﾌ07 ｧ ｦﾌ ｦﾌ ﾀ06 09 ｧ 07ｦﾌ ｦﾌ ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀｦﾌ05ｦﾌ 04ｦﾌ 閨06 縺 ｧ00 07 ﾀ 0905 ｧ , ﾀｦﾌ0707 ｦﾌ ｦ1ｦﾌ ｦﾌ ｦﾌ 04ｦﾌ ｦﾌ 閨07ｦﾌ ｦﾌ ｦﾌ ｦﾌ ｧ0707, ｦﾌ , 0207ｦﾌ 0807ｦﾌ 06ｦﾌ 閨 ｧ0606 ﾀ07 ｧ04 01 ｧ ｧ ｧ ｧ ﾀ ﾀ ﾀｦﾌ07 陦ｧ01 ｧｦﾌ07 ｧ ｦﾌ ｦﾌ ﾀ ｧ ｦﾌ ﾀ 05 ｧ, 0207ｦﾌ 09ｦﾌ 閨06 縺 ｧ ｦﾌ07ｦﾌ0707ｦﾌ05ｦﾌ ｧ ｧ ﾀ ｧ 09ｦﾌ 06 ｧ ｧ 04ｦﾌ ﾀ ｧ00 09ｦﾌ ｧ 陦ｧ05 ｧ07ｦﾌ ｧ- 07ｦﾌ05-3- ﾀ ｧ07 ｦﾌ-09ｦﾌ 隕ﾌ0307ｦﾌ ﾀ ｧ ｯ03 [22] ｦﾌ ﾀ07 ｧ04 ｧ ｦﾌ ｯ03 09ｦﾌ0009ｦﾌ ｧ05 ｧ ｦﾌ Ser ｧ0007ｦﾌ07 H2AX ｧ07 縺03 ｧ00 ﾀ ﾀ0506ｦﾌ00ｦﾌ ｦﾌ06 07 ｧ07 [35]. 6ｦ1ｦﾌ0700 ｦﾌ0507 ｦﾃ ｦ1 ﾀ ﾀ ｦﾌ ｧ ﾀ [36], ｦﾌ07 09 ｧ00ｦﾌ06 陦ｧ ｧ 08 閨06 07 ｧ ﾀｦﾌ ﾀ00 MRN [37]. ｯ ﾀ ｧ06 ｦﾌ03 ｦﾌ06, 09 ｦﾌ07ｦﾌ0707ｦﾌ ﾀｦﾌ07 陦ｧ01 ｧｦﾌ07 ｧｦﾌ04 07 ｧ ﾀ ｧ, ｧ07 閨0801 ｧ ｦﾌ050703ｦﾌ06 ﾀｦﾌ05 ｧ ｦﾌ 0604ｦﾌ , ｧ07 ｧ01 ｧ ｧ ｦﾌ ｧ ﾀ01 ｧ ｯ03 ｦﾃH2AX MRN, ｦﾌ 06 ｧ ｦﾌ04 07 ｧ0606 ﾀ07 ｧ0407ｦﾌ05ｦﾌ ｧ0407ｦﾌ05ｦﾌ ﾀｦﾌ ﾀ00 ｦﾃH2AX-MRN, 04 ﾀｦﾌ07ｦﾌ ｦﾌ06 MRN 閨 ｦﾌ03ｦﾌ 07 ｦﾌ 縺07ｦﾌ ﾀｦﾌ ﾀ00 Mre11- Rad50-Nsb1, ｦﾌ ｧ ｧ ｦﾌ ｧ ｦﾌ06ｦﾌ05ｦﾌ05 ｧ0207ｦﾌ 06 ﾀｦﾌ0603 ｧ07-01 ｧ ｧ [38]. 1 7ｦﾌ 閨 ｦﾌ 閨06 縺 ｧ ｧ07ｦﾌ07ｦﾌ ﾀ00 ｧ ﾀｦﾌ 隕ﾌ ｦﾌ ｧ0000ｦﾌ 陦ｧ ｦﾌ0706, ｦﾌ09 ｧ ｧ ｧ ( ｧ ﾀ ｧ 09 ｦﾌ ﾀ07 ｧ04 ｧ ｦﾌ ), 0207ｦﾌ 09 ｧ- 04ｦﾌ 陦ｧ07 ﾀ ｧ ｧ09 07ｦﾌ ｦﾌ0007 ｧ, 0907 ｧ0407ｦﾌ0608 ｦﾌ / 陦ｧ 01 ｧｦﾌ0707ｦﾌ ｦﾌ 0606 ｧ ｧ00 ﾀ ｦﾌ, 0207ｦﾌ 07 05ｦﾌ05 ｧ ｧ 06 06ｦﾌ ｧ 04 ｦﾌ0007ｦﾌ ｧ0407ｦﾌ05ｦﾌ ｦﾌ ﾀ ｧ [30], 09ｦﾌ00 ﾀｦﾌ0507 ﾀ08 閨 ﾀ ｦﾌ ｦﾌ03 ｦﾌ , 07ｦﾌ, 04 ｦﾌ0705 ｧ02 ｧ06 ｦﾌ07 陦ｧ 01 ｧ ｧ, ｧ 06 09ｦﾌ 06 ｧ ｦﾌ04 07 ｧ ｦﾌ 閨06 縺 ｧ ｦﾌ09ｦﾌ00 06 隕ﾌ ﾀ0001 ｧ ｧｦﾌ0707ｦﾌ ｧ06 04ｦﾌ 07 ｧ ﾀ 0904 ｧ ｦﾌ07 ｧ04ｦﾌ ｧ 縺07ｦﾌ [39]. 6 5 ﾀ ｧ0606 陦ｧ 01 ｧｦﾌ0707ｦﾌ05ｦﾌ 05ｦﾌ 0606 ｧ00 ( ｦﾌ0704ｦﾌ 07ｦﾌ05ｦﾌ 閨06 縺 ｧ00 ｧｦﾌ07 ｧ ｧ ｦﾌ ｧ ｧ00) ｧ06 ｦﾌ ｧ06 ｧ 隕ﾌ04 07 ｧ ｧ060707ｦﾌ04, ｧ00 07ｦﾌ ｦﾌ0603 陦ｧ ｦﾌ04 ﾀ ｦﾌ07 ｧ ｧ [40] ｦﾌ 03ｦﾌ ｦﾌ ﾀ 07 ｦﾌ07 ｧ 隕ﾌ ｦﾌ ｧ00 ｧ06ｦﾌ ｦﾌ ﾀｦﾌ0606 ｧ 隕ﾌ ｧ060707ｦﾌ04 (p =0,0025) ｧ 0007 ｧ ｧ ｧ ｦﾌ ﾀｦﾌ ｦﾌ ｧ09 00ｦﾌ 0009ｦﾌ ｦﾌ ｦﾌ ｧ ｦﾌ0706 [41] DBA/2J, ｦﾌ07 ｧ09 ｧ ﾀ ｧ 陦 0009ｦﾌ05ｦﾌ ﾀ ﾀｦﾌ0606, 09ｦﾌ 閨 ｧ 07ｦﾌ ｦﾌ0608 ｦﾃ-ｦﾌ ｧ09 04 隕ﾌ ｦﾌ 閨 /04- ｧ ﾀ01 ｧ06 00 ｧ ｦﾌ05ｦﾌ ﾀｦﾌ000707ｦﾌ05ｦﾌ 06ｦﾌ 05 (05 ｧ ｦﾌ05ｦﾌ ｯ-05 ｧ0609ｦﾌ01 ｧ07ｦﾌ04) ｦﾌ ﾀ ﾀ ｦﾌ03 03ｦﾌ ｧ ｧ09 ｧ ﾀ 07 ｧ ﾀｦﾌ06 07ｦﾌ 07ｦﾌ 閨 ｧ ｧ ﾀ ｧ, ｧ04ｦﾌ 閨 ｧ ｧ ｦﾌ0007. ｯｦﾌ ｦﾌ06 07 ｧ ﾀｦﾌ 隕ﾌ ｦﾌ04ｦﾌ06 (0, ) ｦﾃ-ｦﾌ ｧ 閨 ｧ ｧ07 ｧ07ｦﾌ06 ｦﾌ ﾀ ｦﾌ 04 ｧ0707ｦﾌ06 閨 ｧ06 ｦﾌ07 04 ｧ07 ｧ ｦﾌ05ｦﾌ05 ｧ ｧ ﾀ ｧ04ｦﾌ [42] 罍 ｦﾌ09 ｦﾌ0706 ﾀ07ｦﾌ ﾀ07 ｦﾃ-ｦﾌ ｧ00 09 ｦﾌ ｧ ｦﾌ 09ｦﾌ05ｦﾌ05 ｧ ﾀ ｧ ｧ ﾀ01 ｧｦﾌ ｦﾌ ( ) ｦﾌ 陦ｧ 01 ｧｦﾌ0707ｦﾌ05ｦﾌ 05ｦﾌ 0606 ｧ00 03 ｧ ﾀｦﾌ07ｦﾌ ｧ ﾀ ｧ06 09 ｦﾌ0106 閨 ｦﾌ 閨 閨 ｦﾌ ｧ ｦﾌ04 00 ﾀ ｧ 01 ｧ ｧ ｧ0009ｦﾌ ﾀｦﾌ06 6ｦ1- ｧ ｧ06 [43, 44] ｧ05 ｧ ｦﾂ ｧ0106 [45] ( 隕ﾌ ｧ ) 閨 ｦﾌ07 ﾀ00 ｧ ﾀｦﾌ05ｦﾌ ｦﾌ ｧ ｧ060707ｦﾌ ｦﾌ ｦﾌ 06 ﾀ ｦﾌ 閨 ｧ ﾀ ｧ. 6 5ｦﾌ ｦﾌ ｦﾌ ｧ ｦﾌ04 00 ﾀ ｧ 01 ｧ ｧ 00ｦﾌ ｦﾌ ｧ ｧ ｦﾌ ｧ06 ｦﾌ070005ｦﾌ ｧ00 09ｦﾌ 閨 ｧ ｧ06 09ｦﾌ 閨 ｧ 閨0607 ｧ00.

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