Parkin在锰致小鼠肝脏毒性中的作用

Effects of Parkin on liver toxicity in mice induced by manganese

目的探讨Parkin蛋白对锰致小鼠肝脏毒性的影响。方法将8周龄、体重22~26 g的SPF级C57B6野生型雄性小鼠及Parkin敲除C57B6雄性小鼠各20只随机分为对照组和染锰组,10只/组。腹腔注射给药(0.01 mL/g),对照组给予生理盐水,染锰组给予50 mg/kg MnCl_(2)·4H 2O,每天15∶00注射1次,每周5 d,周末休息2 d,连续注射4周。记录小鼠体重,计算肝脏系数,ICP-MS检测血液和肝脏中的锰浓度,HE染色观察肝脏病理损伤,试剂盒检测ALT、AST、MDA、SOD水平。结果野生型染锰组小鼠肝脏显微结构出现损伤,血液及肝脏锰浓度、ALT、AST及MDA水平高于野生型对照组小鼠(P<0.05),体重、肝脏重量、肝脏系数、SOD水平低于野生型对照组小鼠(P<0.05)。Parkin敲除染锰组小鼠肝脏显微结构损伤重于野生型染锰组,血液及肝脏锰浓度、ALT、AST及MDA水平高于野生型染锰组小鼠(P<0.05),体重、肝脏重量、肝脏系数、SOD水平低于野生型染锰组小鼠(P<0.05)。结论过量锰暴露可导致小鼠氧化应激损伤,小鼠肝脏结构和功能损伤;敲除Parkin基因可加剧锰诱导的氧化应激损伤,加剧小鼠肝脏结构和功能损伤。

Objective To investigate the effects of Parkin protein on liver toxicity in mice induced by manganese.Methods The Parkin knockout mice and Wild-type mice of the same age were selected and divided into wild-type control group,wild-type manganese treated group,Parkin knockout control group and Parkin knockout manganese treated group.The control group was given 0.01 ml/g normal saline,and the manganese treated group was given 50 mg/kg MnCl_(2)·4H 2O,once a day at 15∶00,5 days a week,for consecutive 4 weeks.Mouse body weight was recorded,liver coefficient was calculated,manganese concentration in blood and liver was measured by ICP-MS;liver pathological injury was observed by HE staining;ALT,AST,MDA and SOD levels were detected by kits.Results The liver microstructure of wild-type manganese treated group was damaged,the blood and liver manganese concentration,ALT,AST and MDA were higher than those of wild-type control group,body weight,liver weight,liver coefficient and SOD was lower than those of wild-type control group.The liver microstructure of Parkin knockout manganese treated group was more severely damaged than those of wild-type manganese group.The blood and liver manganese concentration,ALT,AST and MDA of Parkin knockout manganese treated group were higher than those of wild-type manganese group,body weight,liver weight,liver coefficient and SOD was lower than those of wild-type manganese treated group.Conclusion Excessive manganese exposure can lead to oxidative stress injury and liver structure and function damage in mice.Knockout of Parkin gene can aggravate the damage of manganese,increase oxidative stress,and aggravate the damage of liver structure and function.