黄磷染毒对小鼠肝脏HSP70表达及NO的影响

Effect of Yellow Phosphorus Poisoning on the Expression of HSP70and NO in Mice

[目的]观察黄磷染毒对小鼠HSP70表达及NO的影响 ,以探讨黄磷的毒作用机制 ,寻求黄磷中毒早期健康效应的生物标志物。[方法]通过对小鼠黄磷急性和亚急性毒理实验 ,应用生物化学和分子生物学的技术 ,选取176只健康雄性昆明种小鼠 ,体重18～22g,检测黄磷染毒对HSP70、一氧化氮 (NO)、一氧化氮合酶 (NOS)等指标的影响。染毒时 ,急性剂量_效应关系研究取小鼠32只 ,随机分成4组 ,低、中、高剂量组的染磷量分别为3、6、9mg/kg体重、对照组给予等量的花生油 ,腹腔注射染毒48h。时间_效应关系研究取小鼠64只 ,随机分成8组 ,实验组以9mg/kg体重的剂量一次性腹腔注射染毒 ,分别于染毒0、12、24、48h后断头处死小鼠 ,各组配以相应的对照组。亚急性毒理实验取小鼠80只 ,随机分成以下10组 :0、1、2、3、4周时间组 ,以1.5mg/kg体重的剂量隔日腹腔注射染毒 ,每组配以相应的对照组。[结果]随染磷剂量的增高和染磷时间的延长 ,小鼠肝匀浆HSP70的表达也逐渐升高 ,急性染磷的HSP70表达升高比亚急性染磷明显 ;小鼠肝匀浆NOS活性和NO含量逐渐升高 ,并呈现良好的剂量_反应关系和时间_效应关系。[结论]在黄磷染毒过程中 ,HSP70对细胞起着很重要的保护作用。

The main of this research was to observe the expression of heat shock proteins70(HSP70)and nitric oxide(NO)due to yellowphosphorus poisoning in mice and search for mechanism and bio_markers of early health effect of yellowphosphorus poisoning.Acute and sub_acute toxicity tests in mice were conducted.Biochemistry and molecular biological technologies were to check up and observe the indexes of HSP70,NO and NOS due to yellow phosphorus poisoning in mice.176healthy male Kunming mice weighted18_22g,were grouped randomly.The control group was given the same amountof peanutoil when exposed.The acute toxiciˉty test:for acute dose_response study,32mice were divided randomly into lowdose group(3mg/kg bw),middle dose group(6mg/kg bw),high dose group(9mg/kg bw)and control group.There were8mice per group and exposure time was48hours.For time_response study,64mice were divided into4experiment groups and corresponding control groups,8mice per group.The experimental groups were injected9mg/kg bwof phosphor into abdominal cavity once.Mice were killed0,12,24,48h after injection.In sub_acute toxicity test,80mice were grouped randomly into5experimental groups(0,1,2,3,4_week group)and corresponding control groups.The experimental groups were injected1.5mg/kg bwof phosphor into abdominal cavity each two days.Along with the increasing of yellowphosˉphorus exposure time,HSP70showed more significant increase in acute yellowphosphorus group than that in sub_acute group.NO and NOS activities in mice liver homogenate increased gradually and showed good dose_response and time_response relationship.[Conclusions]Experimental results showed thatHSP70plays veryimportantprotection effectonthe cells inthe process ofyellowphosphoˉrus poisoning.Along with the increase of yellowphosphorus exposure dose and time,NOS activity and NO amount increased gradually in mice liver homogenate with a good dose_response and time_response relationship.It is suggested that NOS and NO are possible to be used as biomarkers of early health effect due to yellowphosphorus poisoning.