Curcumin suppresses N-methyl-N-nitrosourea-induced photoreceptor apoptosis in Sprague-Dawley rats.
Curcumin suppresses N-methyl-N-nitrosourea-induced photoreceptor apoptosis in Sprague-Dawley rats.
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发表时间：
2013-09
期刊：
影响因子：
2.3
通讯作者：
Y. Emoto;K. Yoshizawa;N. Uehara;Y. Kinoshita;T. Yuri;N. Shikata;A. Tsubura
中科院分区：
文献类型：
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作者：
Y. Emoto;K. Yoshizawa;N. Uehara;Y. Kinoshita;T. Yuri;N. Shikata;A. Tsubura
目的视网膜色素变性（Retinitis pigmentosa）是一组遗传性神经退行性疾病，其特征是感光细胞凋亡，最终导致失明。单次腹膜内（i. p.）注射N-甲基-N-亚硝基脲（MNU），一种烷化剂，在7天内引起大鼠感光细胞凋亡。姜黄素是一种多酚类天然产物，具有多能性，包括抗氧化活性。本研究的目的是评估姜黄素对MNU诱导的视网膜变性大鼠模型中感光细胞凋亡的功效。材料和方法7周龄雌性Sprague-Dawley大鼠接受40 mg/kg MNU的单次腹膜内注射。在MNU注射前三天，开始每天腹膜内注射100或200 mg/kg姜黄素，并且每天继续注射一次直至处死。分别于MNU后6、12、24、72 h和7 d处死大鼠，行形态学和形态计量学检查，评价苏木精和伊红染色切片中感光细胞比例和视网膜损伤比例。采用酶联免疫吸附试验（ELISA）检测视网膜8-羟基-2-脱氧鸟苷（8-OHdG）水平，原位TUNEL法检测视网膜光感受器细胞凋亡率。结果姜黄素（200 mg/kg）可显著抑制MNU后7 d视网膜光感受器细胞的丢失（p<0.01），且呈剂量依赖性。在MNU注射后12 h，当MNU引起的氧化性DNA损伤达到峰值时，姜黄素显著降低8-OHdG水平（0.78 vs 0.50 ng/ml）（p<0.05）和TUNEL阳性感光细胞百分比（17.5% vs 10.8%）（p<0.05），分别与MNU暴露、姜黄素未处理的视网膜相比。结论姜黄素通过抑制DNA氧化应激抑制MNU诱导的感光细胞凋亡。这些发现表明，姜黄素可能有助于抑制人类视网膜色素变性的发病和进展。
AIM Retinitis pigmentosa is a group of inherited neurodegenerative human diseases characterized by the loss of photoreceptor cells by apoptosis and lead to eventual blindness. A single intraperitoneal (i.p.) injection of N-methyl-N-nitrosourea (MNU), an alkylating agent, causes photoreceptor cell apoptosis within seven days in rats. Curcumin is a polyphenolic natural product with pluripotent properties including antioxidant activity. The purpose of the present study was to evaluate the efficacy of curcumin against photoreceptor apoptosis in a MNU-induced retinal degeneration rat model. MATERIALS AND METHODS Seven-week-old female Sprague-Dawley rats received a single i.p. injection of 40 mg/kg MNU. Three days prior to MNU injection, daily i.p. injections of 100 or 200 mg/kg curcumin were started, and the injections were continued once daily until sacrifice. Rats were sacrificed at 6, 12, 24 and 72 h, and 7 days after MNU, and their eyes were examined morphologically and morphometrically to evaluate the photoreceptor cell ratio and retinal damage ratio in hematoxylin and eosin-stained sections. Retinal 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were quantified by enzyme-linked immunosorbent assay (ELISA), and the apoptotic cell ratio in photoreceptor cells was determined in situ by TdT-mediated dUTP-digoxigenin nick-end labeling (TUNEL). RESULTS Curcumin (200 mg/kg) significantly (p<0.01) suppressed the loss of photoreceptor cells, as determined by the photoreceptor cell ratio at the central retina seven days after MNU, and this effect was dose-dependent. At 12 h after MNU injection, when the oxidative DNA damage caused by MNU peaked, curcumin significantly reduced the level of 8-OHdG (0.78 vs. 0.50 ng/ml) (p<0.05) and the percentage of TUNEL-positive photoreceptor cells (17.5% vs. 10.8%) (p<0.05) as compared with MNU-exposed, curcumin-untreated retina, respectively. CONCLUSION Curcumin inhibited MNU-induced photoreceptor cell apoptosis by suppressing DNA oxidative stress. These findings indicate that curcumin may help to suppress the onset and progression of human retinitis pigmentosa.