酵母源金属硫蛋白(MT-2)对慢性汞中毒小鼠肝脏损伤的修复作用
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摘要
探讨具有自主知识产权酵母源金属硫蛋白(MT-2)对慢性汞中毒小鼠肝脏损伤的修复作用。让实验小鼠自由饮用氯化汞溶液构建汞中毒模型,以二巯基丙磺酸钠(DMPS)为对照,低、中、高3种剂量酵母源MT-2溶液连续灌胃汞中毒小鼠28 d,然后测定实验小鼠体重、血液生化指标、肝脏汞含量及血清谷丙转氨酶(ALT)和谷草转氨酶(AST)含量,并取肝脏制作HE病理学组织切片,观察肝脏组织病变程度。与模型组小鼠相比,正常组小鼠与各灌胃给药组小鼠体重均高于模型组小鼠,差异不显著(P<0.05)。相较于模型组小鼠,各给药组小鼠血液白细胞、红细胞、血小板计数及血红蛋白含量均有明显的回升,其中高剂量的酵母源金属硫蛋白对于血常规4项指标呈现显著的改善优势(P<0.05)。各给药组小鼠肝脏汞含量及血清ALT、AST含量均显著低于模型组小鼠(P<0.05)。病理学切片观察显示,酵母源MT-2可改善慢性汞中毒小鼠的肝脏损伤状况,可使肿胀肝脏细胞恢复正常形态,其改善效果与剂量呈正相关,且高剂量给药组的改善状态优于DMPS给药组。酵母源MT-2对慢性汞中毒小鼠肝脏损伤具有一定的修复作用,且高剂量酵母源MT-2对汞中毒小鼠肝脏损伤的修复效果明显优于DMPS。
This paper discussed the effect of Metallothionein(MT-2) from yeast with self-owned intellectual property rights on liver damage repair in chronic mercury poisoning mice. Chronic mercury poisoning model group mice built by drinking Hg Cl2 solution for 28 days, and the mice were continuously lavaged low-dose, middle-dose, and high-dose MT-2 after 28 days, the level of weights, blood biochemical index, mercury level of liver, ALT and AST levels of serum were measured after 28 days. Histopathological examinations were carried out to supplement the biochemical results.Compared with model group, normal group and each intragestic administration group was higher than model group, but the differences not significantly(P >0.05), the levels of WBC, RBC, PLT and HGB of each intragestic administration group has a significantly rise, high-dose MT-2 was showed remarkable improvement effect(P >0.05). Mercury level of liver and ALT, AST levels of serum of each intragestic administration group was significantly less than the model group(P>0.05). Liver histopathological examinations showed that MT-2 from yeast can improve the situation of mercury poisoning liver injury in chronic mercury poisoning mice, make the swelling of liver cells to restore normal morphology, it's improvement effects was proportional to the relationship between dose. In effect for the repair of the liver, high-dose MT-2 intragestic administration was better than DMPS intragestic administration. MT-2 had a certain repair of mercury poisoning liver injury in chronic mercury poisoning mice, and the high-dose MT-2 was better than the DMPS.
This paper discussed the effect of Metallothionein(MT-2) from yeast with self-owned intellectual property rights on liver damage repair in chronic mercury poisoning mice. Chronic mercury poisoning model group mice built by drinking Hg Cl2 solution for 28 days, and the mice were continuously lavaged low-dose, middle-dose, and high-dose MT-2 after 28 days, the level of weights, blood biochemical index, mercury level of liver, ALT and AST levels of serum were measured after 28 days. Histopathological examinations were carried out to supplement the biochemical results.Compared with model group, normal group and each intragestic administration group was higher than model group, but the differences not significantly(P >0.05), the levels of WBC, RBC, PLT and HGB of each intragestic administration group has a significantly rise, high-dose MT-2 was showed remarkable improvement effect(P >0.05). Mercury level of liver and ALT, AST levels of serum of each intragestic administration group was significantly less than the model group(P>0.05). Liver histopathological examinations showed that MT-2 from yeast can improve the situation of mercury poisoning liver injury in chronic mercury poisoning mice, make the swelling of liver cells to restore normal morphology, it's improvement effects was proportional to the relationship between dose. In effect for the repair of the liver, high-dose MT-2 intragestic administration was better than DMPS intragestic administration. MT-2 had a certain repair of mercury poisoning liver injury in chronic mercury poisoning mice, and the high-dose MT-2 was better than the DMPS.
引文
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[16]CARVALHO M C,FRANCO J L,GHIZONI H,et al.Effects of 2,3-dimercapto-1-propanesulfonic acid(DMPS)on methylmercury-induced locomotor deficits and cerebellar toxicity in mice[J].Toxicology,2007,239(3):195-203.
[17]储蕙.二巯基丙磺酸钠驱汞治疗引起药疹反应199例分析[J].环境与职业医学,2010,27(3):158-159.
[18]赵之伟,曹冠华,李涛.金属硫蛋白的研究进展[J].云南大学学报(自然科学版),2013,35(3):390-398.
[19]PEREZ-RAFAEL S,MONTEIRO F,DALLINGER R,et al.Cantareus aspersus metallothionein metal binding abilities:The unspecific Ca Cd/Cu MT isoform provides hints about the metal preference determinants in metallothioneins[J].Biochimica et biophysica acta,2014,1844(9):1694-1707.
[2]ZENG Y X,DU Z Y,MJOS S A,et al.Methylmercury increases and eicosapentaenoic acid decreases the relative amounts of arachidonic acid-containing phospholipids in mouse brain[J].Lipids,2016,51(1):61-73.
[3]CARSTEN R HAMANN,BOONCHAI W,WEN L,et al.Spectrometric analysis of mercury content in 549 skinlightening products:Is mercury toxicity a hidden global health hazard?[J].Journal of the American Academy of Dermatology,2014,70(2):281-287.
[4]TRINCHELLA F,ESPOSITO M G,SCUDIERO R.Metallothionein primary structure in amphibians:Insights from comparative evolutionary analysis in vertebrates[J].Comptes Rendus Biologies,2012,335(7):480-487.
[5]LIU F,MA F,KONG G,et al.Zinc supplementation alleviates diabetic peripheral neuropathy by inhibiting oxidative stress and upregulating metallothionein in peripheral nerves of diabetic rats[J].Biological Trace Element Research,2014,158(2):211-8.
[6]李冰,王颖,徐炳政,等.超声波辅助提取酵母源类金属硫蛋白工艺的优化[J].食品与机械,2014,30(3):194-197.
[7]苗兰兰.产金属硫蛋白菌株的诱变育种及蛋白的分离提纯[D].大庆:黑龙江八一农垦大学,2013.
[8]李靖元,张东杰,王颖,等.高产类金属硫蛋白假丝酵母菌株的筛选[J].中国生物制品学杂志,2013,26(11):1585-1587.
[9]CAROCCI A,ROVITO N,SINICROPI M S,et al.Mercury toxicity and neurodegenerative effects[J].Reviews of Environmental Contamination&Toxicology,2014,229(229):1-18.
[10]LIN H,MORRELLFALVEY J L,RAO B,et al.Coupled mercury-cell sorption,reduction,and oxidation on methylmercury production by geobacter sulfurreducens PCA[J].Environmental Science&Technology,2014,48(20):11969-76.
[11]王颖,徐炳政,王欣卉,等.酵母源金属硫蛋白对慢性铅中毒小鼠排铅及肝脏保护作用[J].现代食品科技,2015,31(8):12-17.
[12]徐炳政,张东杰,王颖,张桂芳,陈纯琦,王欣卉.酵母源金属硫蛋白对急性铅中毒小鼠的排铅及过氧化损伤修复作用[J].中国生物制品学杂志,2015,28(11):1142-1146.
[13]徐炳政.酵母源金属硫蛋白排铅及对铅致氧化损伤修复作用的研究[D].大庆:黑龙江八一农垦大学,2015.
[14]郑双来,周建华.无机汞(氯化汞)肾脏毒性机制研究进展[J].国外医学(卫生学分册),2005,32(3):175-179.
[15]SAKAMOTO Y,NAKAMOTO Y,WADA T,et al.Ethyl mercury induces Ca2+uptake through the P 2×7 receptor in a mouse cerebellar microglia cell line[J].Toxicological&Environmental Chemistry,2015,96(9):1-14.
[16]CARVALHO M C,FRANCO J L,GHIZONI H,et al.Effects of 2,3-dimercapto-1-propanesulfonic acid(DMPS)on methylmercury-induced locomotor deficits and cerebellar toxicity in mice[J].Toxicology,2007,239(3):195-203.
[17]储蕙.二巯基丙磺酸钠驱汞治疗引起药疹反应199例分析[J].环境与职业医学,2010,27(3):158-159.
[18]赵之伟,曹冠华,李涛.金属硫蛋白的研究进展[J].云南大学学报(自然科学版),2013,35(3):390-398.
[19]PEREZ-RAFAEL S,MONTEIRO F,DALLINGER R,et al.Cantareus aspersus metallothionein metal binding abilities:The unspecific Ca Cd/Cu MT isoform provides hints about the metal preference determinants in metallothioneins[J].Biochimica et biophysica acta,2014,1844(9):1694-1707.