经口1,2-二氯丙烷致BALB/cA-nu小鼠急性肝损伤的血清学指标变化

Changes of serum markers in acute liver injury induced by oral 1,2-dichloropropane in BALB/cA-nu mice

目的:探究经口1,2-二氯丙烷(1,2-DCP)所致BALB/cA-nu小鼠急性肝损伤特点,为进一步亚慢性、慢性毒性及致癌作用机制研究提供理论参考。方法:于2018年10月,将清洁级健康BALB/cA-nu小鼠随机分成5个染毒剂量组,每组10只,分别一次性灌胃1,2-DCP 860、1150、1500、1950、2535 mg/kg,同时设立空白组和溶剂对照组(玉米油)。染毒后24 h内及时对小鼠眼球采血并取肝胆组织进行病理组织学检查;采用酶联免疫吸附(ELISA)方法检测各组小鼠血清谷丙转氨酶(ALT)、血清总胆红素(TBLI)、C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子α(TNF-α)、肿瘤坏死因子β(TNF-β)的表达变化。结果:随着1,2-DCP染毒剂量的增加,小鼠肝细胞内微泡逐渐增多,炎细胞浸润增多,胆囊未见病理改变。与空白组和溶剂对照组比较,各染毒组小鼠血清ALT含量增高,860、1150、1950、2350 mg/kg染毒组血清IL-6、TNF-β含量增高,1950、2535 mg/kg染毒组血清TNF-α和TBLI含量增高,差异均有统计学意义(P<0.05)。雌性小鼠血清中ALT、TBLI、TNF-β含量差异均有统计学意义(P<0.05);雄性小鼠血清中各指标差异均有统计学意义(P<0.05)。结论:经口1,2-DCP可能引起BALB/cA-nu小鼠急性肝损伤,血清炎症因子表达升高,且雄性小鼠活化的炎性因子种类多于雌性小鼠。

Objective To investigate the characteristics of inflammatory response in BALB/cA-nu mice induced by oral 1,2-dichloropropane(1,2-DCP),and to provides theoretical reference for further study of subchronic,chronic toxicity and carcinogenic mechanism.Methods From October 2018,Clean grade healthy BALB/cA-nu mice were randomly divided into 5 groups with 10 mice in each group.And 860,1150,1500,1950,2535 mg/kg 1,2-DCP were given by gavage respectively.Meanwhile,blank group and solvent control group(corn oil)were set up.Blood samples were collected from eyeballs and liver and bile tissues were collected for histopathological examination within 24 hours after exposure.The expression of alanine aminotransferase(ALT),total bilirubin(TBLI),C-reactive protein(CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and tumor necrosis factor-β(TNF-β)were detected by enzyme-linked immunosorbent assay.Results With the increase of the dose of 1,2-DCP,the number of microbubbles in liver cells and the infiltration of inflammatory cells increased gradually.No pathological changes were found in the gallbladder.Compared with the blank group and solvent control group,the content of serum ALT in each exposure group was increased,the serum levels of IL-6 and TNF-βin 860,1150,1950 and 2350 mg/kg exposure groups were increased,the serum TNF-αand TBLI levels in 1950,2535 mg/kg groups were significantly higher(P<0.05).The levels of ALT,TBLI and TNF-βin serum of female mice were significantly different(P<0.05).There were significant differences in ALT,TBLI,CRP,IL-6,TNF-α,TNF-βin serum of male mice(P<0.05).Conclusion Oral 1,2-DCP may cause acute liver injury in BALB/cA-nu mice and increase the expression of serum inflammatory factors.Moreover,the types of inflammatory factors activated in male mice are more than those in female mice.