丙烯腈亚急性染毒致大鼠肝损伤及其可能机制探讨

Liver injury induced by acrylonitrile subacute exposure in rats and its possible mechanism

目的研究丙烯腈(ACN)亚急性染毒致大鼠肝组织的损伤作用。方法60只SPF级健康成年雄性SD大鼠随机分为对照组(玉米油)、低ACN组(11.5 mg/kg·bw ACN)、中ACN组(23.0 mg/kg·bw ACN)、高ACN组(46.0 mg/kg·bw ACN)、N-乙酰半胱氮酸(NAC)干预组(300.0 mg/kg·bw NAC+46.0 mg/kg·bw ACN),每组12只,灌胃染毒,1次/d,6 d/周,共28 d。末次染毒结束24 h后,心脏采血,摘取肝,计算肝脏器系数,观察肝组织病理学改变,测定血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活力,肝组织过氧化氢酶(CAT)活力、谷胱甘肽(GSH)和丙二醛(MDA)含量。结果低ACN组、高ACN组、NAC干预组大鼠肝脏系数高于对照组(P<0.05);低ACN组、高ACN组大鼠血清ALT活力,中ACN组、高ACN组大鼠血清AST活力高于对照组(P<0.05);高ACN组大鼠血清ALT活力高于NAC干预组(P<0.05);ACN各剂量染毒组、NAC干预组大鼠肝CAT活力低于对照组(P<0.05),高ACN组、NAC干预组大鼠肝GSH含量低于对照组(P<0.05),中ACN组、高ACN组、NAC干预组大鼠肝MDA含量高于对照组(P<0.05);高ACN组大鼠肝MDA含量高于NAC干预组(P<0.05);光学显微镜下,对照组大鼠肝小叶结构清晰,肝索排列整齐,肝细胞形态正常;低ACN组与对照组相比无明显异常变化;中ACN组肝细胞轻度疏松,结构清晰;高ACN组肝细胞肿胀,胞浆疏松,核空泡变;NAC干预组较高ACN组大鼠肝组织损伤减轻。结论ACN亚急性染毒可通过诱导氧化应激使大鼠肝组织脂质过氧化水平发生改变,产生肝损伤作用。

Objective To study the liver injury induced by subacute exposure to ACN in rats.Methods Sixty adult male SPFgrode SD rats were randomly divided into control group(corn oil),low ACN group(11.5 mg/kg·bw ACN),middle ACN group(23.0 mg/kg·bw ACN),high ACN group(46.0 mg/kg·bw ACN),NAC intervention group(300.0 mg/kg·bw NAC+46.0 mg/·bw ACN),12 in each group.The rats were administrated,1 times/day,6 days/week,and 28 days continued,24 hours after the last treatment,the blood samples of all rats were taken from the hearts,and then extracted the liver tissue to calculate the organ coefficient.Hepatic pathological changes were evaluated by optical microscope,the serum expression levels of ALT,AST,AKP and the activity of CAT,the contents of GSH,MDA in liver tissue homogenate were measured by kits.Results The organ coefficient in low ACN,high ACN and NAC intervention groups were higher than control group(P<0.05).The serum expression levels of ALT in low,high ACN groups,the serum expression levels of AST in middle,high ACN groups were higher than control group(P<0.05).The serum expression levels of ALT in high ACN group were higher than NAC intervention group(P<0.05).The activity of CAT in all ACN groups and NAC intervention group were lower than control group(P<0.05),the contents of GSH in high ACN group and NAC intervention group were lower than control group(P<0.05),the contents of MDA in middle,high ACN group and NAC intervention group were higher than control group(P<0.05).The contents of MDA in high ACN group were higher than NAC intervention group(P<0.05).In the view of optical microscope,the structure of the hepatic lobule in control group was clear,the hepatic cords arranged well and the live cell morphology was normal.There were no obvious abnormal changes in low ACN group compared with the control group.The liver cells were mildly loose in middle ACN group,the structure was clear.The liver cells were swollen in high ACN group,cytoplasm was loose,and the nuclear was of vacuole.The damage of liver tissue in NAC intervention group was reduced compared with high ACN group.Conclusion ACN subacute exposure can change the lipid peroxidation level of rat liver tissue by inducing oxidative stress to make the liver injured.