Watanabe Kazushi, Wakatsuki Akihiko, Shinohara Koichi, Ikenoue Nobuo, Yokota Kana, Fukaya Takao
Department of Obstetrics and Gynecology, Kochi Medical School, Oko-cho, Nankoku, Kochi, Japan 783-8505.
J Pineal Res. 2004 Nov;37(4):276-80. doi: 10.1111/j.1600-079X.2004.00167.x.
We investigated the oxidative susceptibility of the brain and the effect of maternally administered melatonin on ischemia/reperfusion-induced cerebral damage in premature fetal rat. Fetal brain mitochondria was separated on the 16th and 19th days of pregnant rats and the respiratory control index (RCI) was measured as an indicator of mitochondrial respiratory activity in the presence or absence of xanthine and xanthine oxidase. The utero-ovarian arteries were occluded bilaterally for 20 min in female rats on day 16 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring circulation for 30 min. A sham operation was performed in control rats. Melatonin (10 mg/kg) or vehicle was injected intraperitoneally into the dams 60 min prior to occlusion. The RCI and concentration of thiobarbituric acid-reactive substances (TBARS) in fetal brain mitochondria were measured. The addition of xanthine and xanthine oxidase significantly decreased mitochondrial RCI at both the 16- and 19-day-old fetal brain. Xanthine and xanthine oxidase-induced reduction in RCI was significantly greater in the 16-day-old fetal brain than that in the fetal brain from the 19th day of pregnancy. Ischemia/reperfusion significantly reduced RCI and elevated TBARS concentrations in the 16-day-old fetal brain mitochondria. Melatonin treatment reversed ischemia/reperfusion-induced reduction in RCI (2.22 +/- 0.10 to 2.53 +/- 0.08, P < 0.01) and elevation in TBARS concentrations (13.50 +/- 1.82 nmol/mg protein to 8.80 +/- 0.78 nmol/mg protein, P < 0.01), resulting in values similar to those in untreated, sham-treated animals. Results indicate that brain mitochondria in the premature fetal rats appear to be more susceptible to oxidative damage. Melatonin administration to pregnant rats may prevent ischemia/reperfusion-induced oxidative mitochondrial damage in premature fetal brain.
我们研究了早产胎鼠脑的氧化易感性以及母体给予褪黑素对缺血/再灌注诱导的脑损伤的影响。在妊娠大鼠的第16天和第19天分离胎脑线粒体，并在存在或不存在黄嘌呤和黄嘌呤氧化酶的情况下测量呼吸控制指数（RCI）作为线粒体呼吸活性的指标。在妊娠第16天对雌性大鼠双侧阻断子宫卵巢动脉20分钟以诱导胎儿缺血。通过解除阻断并恢复循环30分钟实现再灌注。对对照大鼠进行假手术。在阻断前60分钟将褪黑素（10mg/kg）或赋形剂腹腔注射到母鼠体内。测量胎脑线粒体中的RCI和硫代巴比妥酸反应性物质（TBARS）浓度。添加黄嘌呤和黄嘌呤氧化酶显著降低了16日龄和19日龄胎脑的线粒体RCI。黄嘌呤和黄嘌呤氧化酶诱导的RCI降低在16日龄胎脑中比妊娠第19天的胎脑显著更大。缺血/再灌注显著降低了16日龄胎脑线粒体中的RCI并升高了TBARS浓度。褪黑素治疗逆转了缺血/再灌注诱导的RCI降低（从2.22±0.10降至2.53±0.08，P<0.01）和TBARS浓度升高（从13.50±1.82nmol/mg蛋白降至8.80±0.78nmol/mg蛋白，P<0.01），导致值与未处理、假处理动物的值相似。结果表明早产胎鼠的脑线粒体似乎对氧化损伤更敏感。给妊娠大鼠施用褪黑素可能预防早产胎脑缺血/再灌注诱导的氧化线粒体损伤。
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