Hokamura K, Umemura K, Nakamura N, Watanabe M, Takashima T, Nakashima M
Department of Pharmacology, Hamamatsu University School of Medicine, Japan.
Prostaglandins Leukot Essent Fatty Acids. 1998 Sep;59(3):203-7. doi: 10.1016/s0952-3278(98)90064-3.
We investigated effects of lipo-pro-prostaglandin E1 (lipo-[11alpha, 13E, 15S]-11,15-dihydroxy-9-[1-oxobutoxy]-prosta-8, 13-dien-1-oic acid butyl ester), AS-013 in two models of hearing disturbance and equilibrium dysfunction induced by rat inner ear microcirculatory thrombosis. Inner ear microcirculatory thrombosis was induced by photochemical reaction between systemic injection of Rose Bengal and irradiation of green light to the cochlea and vestibule. Photochemical reaction causes endothelial injury followed by platelet adhesion, aggregation and formation of a platelet- and fibrin-rich thrombus. In the hearing disturbance model, a compound cochlear nerve action potential was recorded by electrocochleography every minute. Photochemical reaction induced inner ear microcirculatory thrombosis, followed by disappearance of the action potential. AS-013 significantly (P<0.05) prolonged time to disappearance of the action potential compared with control group. In the equilibrium dysfunction model, the irradiation to the vestibule was applied for 10 min after Rose Bengal injection. The behavior of rats in the swimming test and nystagmus were observed 24 h after the completion of irradiation. In the swimming test, two of 12 animals treated with AS-013 showed no rotating about their longitudinal axes, which indicates equilibrium dysfunction and the duration of well-balanced swimming prolonged. AS-013 suppressed the appearance of nystagmus. These results suggest that lipo-pro-prostaglandin E1, AS-013 may prevent hearing disturbance and equilibrium dysfunction due to inner ear microcirculatory disorders.
我们研究了脂微球载前列地尔（脂微球[11α, 13E, 15S]-11,15-二羟基-9-[1-氧代丁氧基]-前列腺素-8,13-二烯-1-酸丁酯），即AS-013，对大鼠内耳微循环血栓形成所致听力障碍和平衡功能障碍两种模型的影响。通过全身注射孟加拉玫瑰红并对耳蜗和前庭照射绿光之间的光化学反应诱导内耳微循环血栓形成。光化学反应导致内皮损伤，随后血小板黏附、聚集并形成富含血小板和纤维蛋白的血栓。在听力障碍模型中，每分钟通过耳蜗电图记录复合蜗神经动作电位。光化学反应诱导内耳微循环血栓形成，随后动作电位消失。与对照组相比，AS-013显著（P<0.05）延长了动作电位消失的时间。在平衡功能障碍模型中，注射孟加拉玫瑰红后向前庭照射10分钟。照射完成24小时后观察大鼠在游泳试验中的行为和眼球震颤情况。在游泳试验中，接受AS-013治疗的12只动物中有2只未出现绕其纵轴旋转的情况，这表明存在平衡功能障碍，且平衡良好的游泳持续时间延长。AS-013抑制了眼球震颤的出现。这些结果表明，脂微球载前列地尔，即AS-013，可能预防内耳微循环障碍所致的听力障碍和平衡功能障碍。
