Miki Katsuaki, Yoshizawa Katsuhiko, Uehara Norihisa, Yuri Takashi, Matsuoka Yoichiro, Tsubura Airo
Department of Pathology II, Kansai Medical University, Moriguchi Osaka 570-8506, Japan.
In Vivo. 2007 Sep-Oct;21(5):739-44.
There have been no previous studies of the effects of poly(ADP-ribose) polymerase (PARP) inhibitors on N-methyl-N-nitrosourea (MNU)-induced cataractogenesis in rats.
A single intraperitoneal injection of 70 mg/kg MNU was administered to 15-day-old male and female Sprague-Dawley rats. In Experiment 1, rats were then subcutaneously injected with 1000 mg/kg nicotinamide either once or 3 times at 1-week intervals. In Experiment 2, rats were subcutaneously injected once with 50 mg/kg 3-aminobenzamide. For comparison, the following age-matched controls were included: MNU-untreated nicotinamide-injected rats, MNU-untreated 3-aminobenzamide-injected rats, and MNU-untreated PARP-inhibitor-untreated rats. Rats were examined for lens opacity. At 28 days after MNU injection, 10 to 20 rats per group were sacrificed In Experiment 1, at 3 days after MNU injection, 10 rats per group were sacrificed for apoptosis and cell proliferation detection.
MNU caused lens epithelial cell apoptosis in the germinative zone, as indicated by TUNEL staining. However, regardless of MNU treatment lens epithelial cell proliferation was consistently seen in the germinative zone and sporadically seen in the central zone. At 28 days after MNU, mature cataracts were observed Nicotinamide significantly accelerated lens opacity and cataractogenesis, as indicated by a cataract index 3-Aminobenzamide significantly accelerated the development of lens opacity and tended to accelerate cataractogenesis.
The PARP inhibitors nicotinamide and 3-aminobenzamide accelerated MNU-induced cataractogenesis.
此前尚无关于聚（ADP - 核糖）聚合酶（PARP）抑制剂对N - 甲基 - N - 亚硝基脲（MNU）诱导的大鼠白内障形成影响的研究。
对15日龄的雄性和雌性斯普拉格 - 道利大鼠腹腔注射一次70 mg/kg的MNU。在实验1中，随后大鼠皮下注射1000 mg/kg烟酰胺，一次或每隔1周注射3次。在实验2中，大鼠皮下注射一次50 mg/kg的3 - 氨基苯甲酰胺。为作比较，纳入了以下年龄匹配的对照组：未用MNU处理但注射烟酰胺的大鼠、未用MNU处理但注射3 - 氨基苯甲酰胺的大鼠以及未用MNU处理且未用PARP抑制剂处理的大鼠。检查大鼠晶状体混浊情况。在注射MNU后28天，每组处死10至20只大鼠。在实验1中，注射MNU后3天，每组处死10只大鼠用于检测细胞凋亡和细胞增殖。
TUNEL染色显示，MNU导致生发区晶状体上皮细胞凋亡。然而，无论是否用MNU处理，生发区均持续可见晶状体上皮细胞增殖，中央区也偶尔可见。MNU注射后28天，观察到成熟白内障。白内障指数表明，烟酰胺显著加速晶状体混浊和白内障形成。3 - 氨基苯甲酰胺显著加速晶状体混浊的发展，并倾向于加速白内障形成。
PARP抑制剂烟酰胺和3 - 氨基苯甲酰胺加速了MNU诱导的白内障形成。
