【摘要】 目的探讨磺草酮亚慢性暴露对大鼠酪氨酸代谢的影响及其角膜毒性。方法磺草酮(0.1、0.5、5、50和100 mg/kg·d)剂量灌胃染毒90 d。实验结束后分别测定大鼠肝脏酪氨酸氨基转移酶[tyrosine aminotransferase(TAT)]、4-羟苯丙酮酸二加氧酶[4-hydroxyphenylpyruvate dioxygenase(HPPD)]、尿黑酸氧化酶[homogentisic acid oxidase(HGO)]活力及血浆和房水酪氨酸浓度,并制备角膜组织病理切片;在实验前及实验期间用裂隙灯显微镜观察大鼠角膜损伤情况。结果与对照组相比,各染毒组大鼠肝脏TAT活力均显著性升高(P<0.001)、HPPD活力均显著性降低(P<0.001)、HGO活力高剂量组(5、50和100 mg/kg·d)均显著性降低(P<0.001),各染毒组大鼠血浆和房水酪氨酸浓度均显著性升高(P<0.001);实验期间磺草酮引发高剂量染毒组大鼠角膜损伤,到90 d实验结束时染毒组(5、50和100 mg/kg·d)大鼠角膜损伤发生数分别为25.0%、75.0%(P<0.001)和62.5%(P<0.001);组织病理学结果显示磺草酮引发大鼠角膜炎。结论磺草酮能有效抑制大鼠肝脏HPPD活力,干扰正常酪氨酸代谢,并诱发大鼠酪氨酸血症,进而导致酪氨酸在房水中蓄积,并最终引发大鼠角膜损伤。更多还原

【Abstract】 Objective To investigate the effects of subchronic exposure to sulcotrione on tyrosine catabolism in rats and its corneal toxicity. Methods Sulcotrione was administered orally at dose of 0. 1,0. 5,5,50,500 mg / kg·d for 90 d. At the end of the experiment,the activities of hepatic TAT,HPPD,HGO and the level of tyrosine in plasma and aqueous humor were analyzed,and the pathological section of corneal tissues were prepared. The eyes of all rats were examined by a slit lamp microscope both pre-test and the study period.Results Compared to the control group,the activities of hepatic TAT at each dose level were insignificantly induced( P < 0. 001),HPPD were markedly inhibited( P < 0. 001),HGO at higher dose groups( 5,50 and 100 mg / kg·d) were markedly reduced( P < 0. 001),the level of tyrosine in plasma and aqueous humor were significantly increased( P < 0. 001),and corneal lesions were produced by sulcotrione at higher dose groups during the study period,and repeated oral administration of sulcotrione at doses of 5,50,and 100 mg / kg·d for 90 days produced corneal lesions with an incidence of 25. 0%,75. 0%( P < 0. 001) and 62. 5%( P < 0. 001),respectively,also under light microscopy revealed that sulcotrione induced keratitis in rats. Conclusion Sulcotrione can potenlly inhibit hepatic HPPD,altering tyrosine catabolism,causing tyrosinemia,leading to the accumulation of tyrosine in aqueous humor,and induce corneal lesion in rats eventually.更多还原