Oncolyn对温石棉所致大鼠氧化损伤影响的实验研究

Effect of Oncolyn on oxidative damage caused by chrysotile in rats

目的探讨温石棉对实验大鼠氧化损伤的影响以及Oncolyn的缓解作用。方法Wistar大鼠随机分为对照组、石棉组和Oncolyn组,应用支气管灌注的方法给予大鼠温石棉5mg/ml,同时经口给入Oncolyn40d,剂量为1.5g/(kg·d),检测肺泡巨噬细胞中DNA损伤状况以及血液和肺脏中NO、NOS和抗氧化酶SOD、CAT、GSHPx、GST的活性。结果石棉组肺泡巨噬细胞DNA链断裂增加,表现为彗星出现率和DNA迁移长度增加;血液中NO和NOS水平和SOD、GSHPx活性增加,而GST活性下降;而肺组织中NOS、SOD、GSHPx和GST的活性均下降,MDA含量增加。应用Oncolyn预防后,肺泡巨噬细胞DNA损伤下降;血液中NO、NOS的水平以及SOD活性下降,而GSHPx、GST、CAT活性上升;肺组织中抗氧化酶活性增加,MDA含量下降。结论Oncolyn对温石棉所致机体氧化损伤有一定的缓解作用。

Objective To explore the neutralization of Oncolyn on oxidative damage in rats induced by chrysotile. Method Male Wistar rats, weighing 200-250g, were divided into three groups： control group, chrysotile exposure group and Oncolyn intervening group. Animals were intratracheally instilled with sterile saline （control group） or saline suspensions of chrysotile （chrysotile group and Oncolyn group）, the rats of Oncolyn group were also administrated with Oncolyn [dissolved in saline, 1.5 g,/ （kg·d）] by oral after instillation of chrysotile. The status of DNA damage in AM, the level of NO and the activities of NOS, SOD, CAT （catalase）, G-ST （glutathione stransferase）, GSH-Px were measured both in blood and lung tissue were measured. Result The DNA chain break （percent of comet cells 63.2% and the length of DNA migration 51.17μm） in AM of rats from chrysotile group was more serious than that of control group （9.2% and 24.45μm）, and the NO level and the activities of NOS, SOD, CAT, GSH-Px in blood were higher than that of the controis, but the activity of G-ST was lower than that of the control group. Meanwhile in lung tissne the activities of NOS, SOD, GSH-Px, G-ST in chrysotile group were lower than the corresponding values in control group. When rats were administered with Oncolyn, the percent of comet cell （29.3%） and length of DNA migration （33.11μm） decreased than the values of chrysotile group, the levels of NO, NOS, MDA decreased and the activities of anti-oxidative enzymes such as SOD. GSH-Px, G-ST were increased compared with chrysotile group. Conclusion Oncolyn shows good effect in inhibiting generation of NO, NOS, elevating the activity of antioxidation enzyme etc., then exerted the oxidative damage on DNA of AM induced by chrysotile in some degree.