Caspase-3 inhibitor rescues N-methyl-N-nitrosourea-induced retinal degeneration in Sprague-Dawley rats
Caspase-3 inhibitor rescues N-methyl-N-nitrosourea-induced retinal degeneration in Sprague-Dawley rats
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DOI：
10.1006/exer.2000.0921
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发表时间：
2000-12-01
影响因子：
3.4
通讯作者：
Tsubura, A
中科院分区：
文献类型：
--
作者：
Yoshizawa, K;Yang, JH;Tsubura, A
研究了半胱天冬酶-3抑制剂对N-甲基-N-亚硝基脲（MNU）诱导的视网膜变性的影响。给50日龄雌性Sprague-Dawley大鼠腹腔注射60 mg/kg MNU，并在MNU后0和10 h玻璃体内注射4000 ng Ac-DEVD-CHO（一种caspase-3抑制剂）两次。在外周和中央视网膜中，通过TUNEL标记计算MNU治疗后24小时的感光细胞凋亡指数，并根据视网膜厚度和视网膜损伤比（受损视网膜的长度：整个视网膜长度）评估MNU治疗后7天的视网膜损伤。在MNU治疗的大鼠中，MNU治疗后24小时，外周视网膜的TUNEL指数为79.5%，中央视网膜的TUNEL指数为83.7%，而Ac-DEVD-CHO注射分别将其显着降低至59.7%和71.8%。总视网膜厚度7天后MNU是38妈妈在周边和75妈妈在中央视网膜。Ac-DEVD-CHO注射将这些值分别增加至72和77 μ m。MNU后7天视网膜损伤率为98.5%。Ac-DEVD-CHO进样将该值显著降低至54.4%。使用半胱天冬酶-3抑制剂可有效抑制MNU诱导的视网膜细胞凋亡，并可能成为人类视网膜色素变性的治疗干预措施。(C)北京大学出版社.
The effect of a caspase-3 inhibitor on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration was investigated. Sixty mg kg(-1) MNU was given intraperitoneally to 50 day old female Sprague-Dawley rats, and 4000 ng Ac-DEVD-CHO, a caspase-3 inhibitor, was injected intravitreally twice at 0 and 10 hr after MNU. In both peripheral and central retina, an apoptotic index of the photoreceptor cells 24 hr after MNU treatment was calculated by TUNEL labeling, and retinal damage 7 days after MNU treatment was evaluated from retinal thickness and a retinal damage ratio (length of damaged retina:whole retinal length). In MNU-treated rats, the TUNEL index 24 hr post-MNU was 79.5% in the peripheral and 83.7% in the central retina, while the Ac-DEVD-CHO injection significantly reduced it to 59.7 and 71.8%, respectively. Total retinal thickness 7 days after MNU was 38 mum in the peripheral and 75 mum in the central retina. Ac-DEVD-CHO injection increased these values to 72 and 77 mum, respectively. The retinal damage ratio 7 days after MNU was 98.5%. Ac-DEVD-CHO injection significantly reduced this value to 54.4%. The use of a caspase-3 inhibitor was effective in the suppression of MNU-induced retinal apoptosis and may be a therapeutic intervention in human retinitis pigmentosa. (C) 2000 Academic Press.