酵母源金属硫蛋白对慢性汞中毒小鼠排汞及肾脏损伤的修复作用
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摘要
探讨具有自主知识产权的酵母源金属硫蛋白(MT-1、MT-2)对慢性汞中毒小鼠排汞及汞致肾脏损伤修复作用。SPF级昆明雄性种鼠经氯化汞染毒,灌胃酵母源金属硫蛋白及二巯基丙磺酸钠(DMPS)28 d后测定小鼠体质量、肾脏湿重及肾指数、血液及肾脏汞离子含量、血清尿素氮(BUN)、肌酐(CREA)指标水平,并取肾脏组织制作HE病理学染色切片,观察肾脏病变程度及灌胃药物对肾脏组织的修复情况。试验结果表明,相较于正常对照组,模型对照组小鼠体质量显著下降(P<0.05),肾指数、血液及肾脏汞含量、BUN及CREA水平显著升高(P<0.05)。HE染色切片显示模型对照组小鼠肾脏组织出现肾小球及系膜细胞增生,并伴有大量炎性细胞浸润及组织坏死现象。灌胃给药28 d后,各灌胃给药组小鼠体质量较模型对照组显著增加(P<0.05),酵母源金属硫蛋白高剂量及DMPS给药组小鼠肾指数、血液及肾脏汞含量、BUN及CREA水平显著下降(P<0.05),且病理学切片显示酵母源金属硫蛋白高剂量给药可修复小鼠肾脏受损组织细胞,水肿增生及坏死现象明显减轻。两种酵母源金属硫蛋白对慢性汞中毒小鼠具有良好的排汞及修复汞致小鼠肾脏损伤的作用。
To investigate the prosthetic effect of metallothioneins from yeast with self-owned intellectual property rights in kidney damage and mercury ion expelling on chronic mercury poisoning mice. SPF KM mice by mercuric chloride solutions and the chronic mercury poisoning mice were continuously lavaged metallothioneins from yeast(MT-1, MT-2) and DMPS for 28 days. The level of body mass, mercury ion level of blood and kidney, BUN and CREA level of serum were measured after 28 days, histopathological examinations were carried out to supplement the kidney biochemical results. The result showed that the body mass level of model group mice was decreased significantly(P<0.05), and the kidney index, mercury ion level of blood, BUN and CREA level of serum were increased significantly to compared with normal group mice(P<0.05), kidney histopathological examinations showed that the glomerular and mesangial appeared proliferation and associated with inflammatory cell infiltration. After lavaged 28 days, the body mass level of each intragastric administration group mice were increased significantly to compared with model group mice(P<0.05), the kidney index, mercury ion level of blood and kidney, BUN and CREA level of serum were decreased significantly(P<0.05),the histopathological examinations showed that the high-dose metallothioneins from yeast could repair impaired cells of kidney, edematous and necrotic phenomenon alleviate obviously. Two kinds of metallothioneins from yeast had the obvious effects on mercury expelling and kidney damage repairing.
To investigate the prosthetic effect of metallothioneins from yeast with self-owned intellectual property rights in kidney damage and mercury ion expelling on chronic mercury poisoning mice. SPF KM mice by mercuric chloride solutions and the chronic mercury poisoning mice were continuously lavaged metallothioneins from yeast(MT-1, MT-2) and DMPS for 28 days. The level of body mass, mercury ion level of blood and kidney, BUN and CREA level of serum were measured after 28 days, histopathological examinations were carried out to supplement the kidney biochemical results. The result showed that the body mass level of model group mice was decreased significantly(P<0.05), and the kidney index, mercury ion level of blood, BUN and CREA level of serum were increased significantly to compared with normal group mice(P<0.05), kidney histopathological examinations showed that the glomerular and mesangial appeared proliferation and associated with inflammatory cell infiltration. After lavaged 28 days, the body mass level of each intragastric administration group mice were increased significantly to compared with model group mice(P<0.05), the kidney index, mercury ion level of blood and kidney, BUN and CREA level of serum were decreased significantly(P<0.05),the histopathological examinations showed that the high-dose metallothioneins from yeast could repair impaired cells of kidney, edematous and necrotic phenomenon alleviate obviously. Two kinds of metallothioneins from yeast had the obvious effects on mercury expelling and kidney damage repairing.
引文
[1] LI P, FENG X B, QIU G L, et al. Mercury pollution in Asia:A review of the contaminated sites[J].Journal of Hazardous Materials, 2009, 168(2/3):591-601.
[2] PINHEIRO M C, CRESPO-L M E, VIEIRA J L,et al. Mercury pollution and childhood in Amazon riverside villages[J]. Environment International, 2007,33(1):56-61.
[3] MALGORZATA R, KINGA D, GABRIELA B, et al. Organomercury compounds in environmental samples:Emission sources, toxicity, environmental fate,and determination[J]. Critical Reviews in Environmental Sciences&Stechnology, 2014, 44(6):638-704.
[4] LOHREN H, BORNHORST J, GALLA H J, et al.The blood-cerebrospinal fluid barrier-first evidence for an active transport of organic mercury compounds out of the brain[J]. Metallomics, 2015, 7(10):1420-1430.
[5]陈子安,聂志勇,李万华,等.汞的肾毒性及治疗研究进展[J].中国药理学与毒理学杂志, 2016, 30(3):286-290.
[6]钟丽,朱士新,白莹,等.汞作业工人肾损伤早期指标变化及其影响因素[J].中华劳动卫生职业病杂志, 2014, 32(12):4-10.
[7] 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.
[8]尹磊淼,王宇,徐玉东,等.金属硫蛋白-2(MT-2)表达调控和蛋白相互作用研究进展[J].复旦学报(医学版), 2014, 41(1):121-125.
[9]汤晓燕,陈丽杰,袁文杰.金属硫蛋白应用于重金属吸附的研究进展[J].现代化工, 2014, 34(6):32-36.
[10]陈春亮,马胜伟,王学锋.汞、镉离子急性污染对紫红笛鲷肝脏金属硫蛋白的胁迫效应[J].农业环境科学学报, 2014, 33(8):1493-1499.
[11]彭新君,徐丽霞,刘平安,等.家兔肝脏中锌-金属硫蛋白提取工艺的优化[J].药物生物技术, 2004, 11(2):99-103.
[12]党蕊叶,齐凡,赵淑琳,等.兔肝金属硫蛋白提取工艺研究[J].西北农业学报, 2012, 21(6):22-25.
[13]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.
[14]苗兰兰,张东杰,王颖.复合诱变高产金属硫蛋白酵母菌株的筛选[J].食品科学, 2013, 34(19):261-264.
[15]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.
[16]王月,张东杰,王颖,等.响应面优化双水相萃取分离酵母源MT工艺[J].食品科学, 2015, 36(10):54-58.
[17]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.
[18]徐炳政,张东杰,王颖,等.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.
[19]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.
[20]董书清.血清肌酐、尿素氮的检测值及其比值与肾脏损害的探讨[J].中国医药指南, 2011, 9(36):136-137.
[21]胡玉海.血肌酐、血尿素氮评价慢性肾脏病患者肾功能时与年龄的相关性研究[J].国际检验医学杂志,2013, 34(10):1313-1314.
[22]郑植元,李岑,张明,等.含HgS传统药物朱砂和佐太中汞的胃肠道溶出及吸收蓄积研究[J].中国中药杂志, 2015, 40(12):2455-2460.
[23] XU S Z, ZENG B, DASKOULIDOU N, et al. Activation of TRPC cationic channels by mercurial compounds confers the cytotoxicity of mercury exposure[J]. Toxicological Sciences an Official Journal of the Society of Toxicology, 2012, 125(1):56-68.
[24] ZALUPS R K. Molecular interactions with mercury in the kidney[J]. Pharmacological Reviews, 2000, 52(52):113-43.
[25]陈敏,高晓钦,荆俊杰,等.氯化汞染毒小鼠各脏器中汞和微量元素的测定及分析[J].光谱实验室,2000, 17(5):525-527.
[26] BRADBERRY S M. Metals(cobalt, copper, lead,mercury)[J]. Medicine, 2016, 44(3):182-184.
[2] PINHEIRO M C, CRESPO-L M E, VIEIRA J L,et al. Mercury pollution and childhood in Amazon riverside villages[J]. Environment International, 2007,33(1):56-61.
[3] MALGORZATA R, KINGA D, GABRIELA B, et al. Organomercury compounds in environmental samples:Emission sources, toxicity, environmental fate,and determination[J]. Critical Reviews in Environmental Sciences&Stechnology, 2014, 44(6):638-704.
[4] LOHREN H, BORNHORST J, GALLA H J, et al.The blood-cerebrospinal fluid barrier-first evidence for an active transport of organic mercury compounds out of the brain[J]. Metallomics, 2015, 7(10):1420-1430.
[5]陈子安,聂志勇,李万华,等.汞的肾毒性及治疗研究进展[J].中国药理学与毒理学杂志, 2016, 30(3):286-290.
[6]钟丽,朱士新,白莹,等.汞作业工人肾损伤早期指标变化及其影响因素[J].中华劳动卫生职业病杂志, 2014, 32(12):4-10.
[7] 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.
[8]尹磊淼,王宇,徐玉东,等.金属硫蛋白-2(MT-2)表达调控和蛋白相互作用研究进展[J].复旦学报(医学版), 2014, 41(1):121-125.
[9]汤晓燕,陈丽杰,袁文杰.金属硫蛋白应用于重金属吸附的研究进展[J].现代化工, 2014, 34(6):32-36.
[10]陈春亮,马胜伟,王学锋.汞、镉离子急性污染对紫红笛鲷肝脏金属硫蛋白的胁迫效应[J].农业环境科学学报, 2014, 33(8):1493-1499.
[11]彭新君,徐丽霞,刘平安,等.家兔肝脏中锌-金属硫蛋白提取工艺的优化[J].药物生物技术, 2004, 11(2):99-103.
[12]党蕊叶,齐凡,赵淑琳,等.兔肝金属硫蛋白提取工艺研究[J].西北农业学报, 2012, 21(6):22-25.
[13]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.
[14]苗兰兰,张东杰,王颖.复合诱变高产金属硫蛋白酵母菌株的筛选[J].食品科学, 2013, 34(19):261-264.
[15]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.
[16]王月,张东杰,王颖,等.响应面优化双水相萃取分离酵母源MT工艺[J].食品科学, 2015, 36(10):54-58.
[17]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.
[18]徐炳政,张东杰,王颖,等.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.
[19]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.
[20]董书清.血清肌酐、尿素氮的检测值及其比值与肾脏损害的探讨[J].中国医药指南, 2011, 9(36):136-137.
[21]胡玉海.血肌酐、血尿素氮评价慢性肾脏病患者肾功能时与年龄的相关性研究[J].国际检验医学杂志,2013, 34(10):1313-1314.
[22]郑植元,李岑,张明,等.含HgS传统药物朱砂和佐太中汞的胃肠道溶出及吸收蓄积研究[J].中国中药杂志, 2015, 40(12):2455-2460.
[23] XU S Z, ZENG B, DASKOULIDOU N, et al. Activation of TRPC cationic channels by mercurial compounds confers the cytotoxicity of mercury exposure[J]. Toxicological Sciences an Official Journal of the Society of Toxicology, 2012, 125(1):56-68.
[24] ZALUPS R K. Molecular interactions with mercury in the kidney[J]. Pharmacological Reviews, 2000, 52(52):113-43.
[25]陈敏,高晓钦,荆俊杰,等.氯化汞染毒小鼠各脏器中汞和微量元素的测定及分析[J].光谱实验室,2000, 17(5):525-527.
[26] BRADBERRY S M. Metals(cobalt, copper, lead,mercury)[J]. Medicine, 2016, 44(3):182-184.