乳酸菌对铜暴露大鼠肝功能及氧化应激的影响
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摘要
目的观察相对低剂量的铜暴露对大鼠肝脏功能和氧化应激水平的影响,并探讨乳酸菌干预对铜暴露引起的大鼠肝功能损伤和氧化应激水平变化的影响。方法取雄性Wistar大鼠共64只,随机分为高铜组(14.000mg/kg)、中铜组(3.500mg/kg)、低铜组(0.875 mg/kg)、高铜+乳酸菌组(14.000 mg/kg铜+乳酸菌)、中铜+乳酸菌组(3.500mg/kg铜+乳酸菌)、低铜+乳酸菌组(0.875mg/kg铜+乳酸菌)、乳酸菌组和空白对照组,每组8只,分别给予相应溶液灌胃干预30d。干预结束后,观察大鼠肝脏病理变化,肝、脾和胸腺指数,检测大鼠肝功能指标谷丙转氨酶(ALT)、谷草转氨酶(AST)和清蛋白(ALB),肝组织氧化应激相关指标超氧化物歧化酶(SOD)、丙二醛(MDA)水平。结果病理观察显示,高铜+乳酸菌组大鼠的肝损伤较高铜组明显改善。生化分析结果显示,高铜组、中铜组和低铜组的AST、ALT较空白对照组升高,ALB较空白对照组降低,差异均有统计学意义(F=8.712~19.134,P<0.05);高铜+乳酸菌组与高铜组比较、中铜+乳酸菌组与中铜组比较,AST、ALT均明显降低,ALB明显升高,差异有显著性(t=2.257~10.199,P<0.05);低铜+乳酸菌组与低铜组比较,ALT明显降低,ALB明显升高,差异有显著性(t=3.161、4.032,P<0.05)。氧化应激指标分析显示,与空白对照组比较,高铜组和中铜组SOD活性显著降低,MDA含量升高,差异有统计学意义(F=28.900、119.900,P<0.05);高铜+乳酸菌组与高铜组比较、中铜+乳酸菌组与中铜组比较,SOD活性显著升高,MDA含量显著降低,差异有显著性(t=2.069~5.214,P<0.05)。结论相对低剂量的铜能影响大鼠肝脏功能和氧化应激反应;在乳酸菌的干预下,高、中、低3个硫酸铜剂量组大鼠的肝脏功能和氧化应激均得到不同程度改善。
Objective To investigate the influence of low-dose Copper exposure on liver function and oxidative stress in rats,as well as the effect of Lactobacillus(LAB)intervention on liver impairment and changes in oxidative stress level caused by Copper exposure. Methods A total of 64 Wistar rats were randomly divided into high-Copper group(14.000mg/kg),mediumCopper group(3.500mg/kg),low-Copper group(0.875mg/kg),high-Copper+LAB group(14.000mg/kg Copper+LAB),medium-Copper+LAB group(3.500mg/kg Copper+LAB),low-Copper+LAB group(0.875mg/kg Copper+LAB),LAB group,and blank control group,with 8rats in each group.The rats were treated by gavage for 30 d.After the treatment ended,pathological changes of the liver were observed,liver,spleen,and thymus indices were calculated,and the levels of liver function parameters,alanine aminotransferase(ALT),aspartate aminotransferase(AST),and albumin(ALB),and oxidative stress indices,superoxide dismutase(SOD)and malondialdehyde(MDA),were measured. Results Pathological examination showed that compared with the high-Copper group,the high-Copper+LAB group had significant improvements in liver injury.The results of biochemical analysis showed that compared with the blank control group,the high-,medium-,and low-Copper groups had significant increases in AST and ALT and a significant reduction in ALB(F=8.712-19.134,P<0.05).Compared with the high-Copper group or the medium-Copper group,the high-Copper+LAB group or the medium-Copper+LAB group had significant reductions in AST and ALT and a significant increase in ALB(t=2.257-10.199,P<0.05).Compared with the low-Copper group,the lowCopper+LAB group had a significant reduction in ALT and a significant increase in ALB(t=3.161,4.032;P<0.05).The analysis of oxidative stress indices showed that compared with the blank control group,the high-and medium-Copper groups had a significant reduction in SOD activity and a significant increase in the content of MDA(F=28.900,119.900;P<0.05).Compared with the high-Copper group or the medium-Copper group,the high-Copper+LAB group or the medium-Copper+LAB group had a significant increase in SOD level and a significant reduction in the content of MDA(t=2.069-5.214,P<0.05). Conclusion A relatively low dose of Copper can affect liver function and oxidative stress response in rats,and LAB intervention helps to improve liver function and oxidative stress in high-,medium-,and low-dose Copper sulfate groups.
Objective To investigate the influence of low-dose Copper exposure on liver function and oxidative stress in rats,as well as the effect of Lactobacillus(LAB)intervention on liver impairment and changes in oxidative stress level caused by Copper exposure. Methods A total of 64 Wistar rats were randomly divided into high-Copper group(14.000mg/kg),mediumCopper group(3.500mg/kg),low-Copper group(0.875mg/kg),high-Copper+LAB group(14.000mg/kg Copper+LAB),medium-Copper+LAB group(3.500mg/kg Copper+LAB),low-Copper+LAB group(0.875mg/kg Copper+LAB),LAB group,and blank control group,with 8rats in each group.The rats were treated by gavage for 30 d.After the treatment ended,pathological changes of the liver were observed,liver,spleen,and thymus indices were calculated,and the levels of liver function parameters,alanine aminotransferase(ALT),aspartate aminotransferase(AST),and albumin(ALB),and oxidative stress indices,superoxide dismutase(SOD)and malondialdehyde(MDA),were measured. Results Pathological examination showed that compared with the high-Copper group,the high-Copper+LAB group had significant improvements in liver injury.The results of biochemical analysis showed that compared with the blank control group,the high-,medium-,and low-Copper groups had significant increases in AST and ALT and a significant reduction in ALB(F=8.712-19.134,P<0.05).Compared with the high-Copper group or the medium-Copper group,the high-Copper+LAB group or the medium-Copper+LAB group had significant reductions in AST and ALT and a significant increase in ALB(t=2.257-10.199,P<0.05).Compared with the low-Copper group,the lowCopper+LAB group had a significant reduction in ALT and a significant increase in ALB(t=3.161,4.032;P<0.05).The analysis of oxidative stress indices showed that compared with the blank control group,the high-and medium-Copper groups had a significant reduction in SOD activity and a significant increase in the content of MDA(F=28.900,119.900;P<0.05).Compared with the high-Copper group or the medium-Copper group,the high-Copper+LAB group or the medium-Copper+LAB group had a significant increase in SOD level and a significant reduction in the content of MDA(t=2.069-5.214,P<0.05). Conclusion A relatively low dose of Copper can affect liver function and oxidative stress response in rats,and LAB intervention helps to improve liver function and oxidative stress in high-,medium-,and low-dose Copper sulfate groups.
引文
[1]李万立,罗海吉.微量元素铜与人类疾病关系的研究进展[J].微量元素与健康研究,2008,25(1):62-65.
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[3]田驰,黄夏梦,王霆.临床常用铜离子螯合剂药代动力学和不良反应研究进展[J].实用肝脏病杂志,2015(2):221-224.
[4]CHANG Y C,CHOI D,KIKUCHI S.Enhanced extraction of heavy metals in the two-step process with the mixed culture of Lactobacillus bulgaricus and Streptococcus thermophilus[J].Bioresource Technology,2012,103(1):477-480.
[5]MOSIER A P,BEHNKE J,JIN E T,et al.Microbial biofilms for the removal of Cu2+from CMP wastewater[J].Journal of Environmental Management,2015,160(67/72):67-72.
[6]SCHUT S,ZAUNER S,HAMPEL G,et al.Biosorption of Copper by wine-relevant lactobacilli[J].International Journal of Food Microbiology,2011,145(1):126-131.
[7]张晓黎,吴兴壮,张华.乳酸菌功能作用及其在生产中的应用[J].农业工程技术·农产品加工业,2015(5):36-39.
[8]靳克林.2011年濮阳市食品安全风险调查分析[J].河南预防医学杂志,2012,23(4):313-315.
[9]陈志,张婷,蒋芳,等.绵阳市食品中金属污染物监测结果分析[J].现代预防医学,2013,40(5):822-824.
[10]MILNE D B,NIELSEN F H.Effects of a diet low in Copper on copper-status indicators in postmenopausal women[J].The American Journal of Clinical Nutrition,1996,63(3):358-364.
[11]MILNE D B,DAVIS C D,NIELSEN F H.Low dietary Zinc alters indices of Copper function and status in postmenopausal women[J].Nutrition(Burbank,Los Angeles County,Calif.),2001,17(9):701-708.
[12]ZATTA P,DRAGO D,ZAMBENEDETTI P,et al.Accumulation of Copper and other metal ions and metallothioneinⅠ/Ⅱexpression in the bovine brain as a function of aging[J].Journal of Chemical Neuroanatomy,2008,36(1):1-5.
[13]SINGH M M,SINGH R,KHARE A,et al.Serum Copper in myocardial infarction--diagnostic and prognostic significance[J].Angiology,1985,36(8):504-510.
[14]KOK F J,VAN DUIJN C M,HOFMAN A,et al.Serum Copper and Zinc and the risk of death from cancer and cardiovascular disease[J].American Journal of Epidemiology,1988,128(2):352-359.
[15]SALONEN J T,SALONEN R,KORPELA H,et al.Serum Copper and the risk of acute myocardial infarction:aprospective population study in men in eastern Finland[J].American Journal of Epidemiology,1991,134(3):268-276.
[16]ZOWCZAK M,ISKRA M,PASZKOWSKI J,et al.Oxidase activity of ceruloplasmin and concentrations of Copper and Zinc in serum of cancer patients[J].Journal of Trace Elements in Medicine and Biology:Organ of the Society for Minerals and Trace Elements(GMS),2001,15(2/3):193-196.
[17]ODONOHUE J W,REID M A,VARGHESE A,et al.Micronodular cirrhosis and acute liver-failure due to chronic copper self-intoxication[J].European Journal of Gastroenterology&Hepatology,1993,5(7):561-562.
[18]ARAYA M,OLIVARES M,PIZARRO F,et al.Copper exposure and potential biomarkers of Copper metabolism[J].Biometals:an International Journal on the Role of Metal Ions in Biology,Biochemistry,and Medicine,2003,16(1):199-204.
[19]陈通克,管敏强,李翔,等.铜中毒对SD大鼠肝的影响研究[J].广东微量元素科学,2010,17(10):17-21.
[20]李万立,罗海吉,查龙应.铜过量小鼠肝损伤模型的建立及各项指标的观察研究[J].热带医学杂志,2008,8(12):1210-1212.
[21]万小华,罗小平.铜负荷大鼠肝脏FAS、FASL的表达及其意义[J].实用临床医学,2007,8(9):1-3.
[22]文彩虹.宜昌市土家族地区子宫颈癌筛查及其与微量元素的关系[D].广州:南方医科大学,2013.
[23]迟菲菲,田丰伟,王刚,等.植物乳杆菌LP1001缓解小鼠酒精性肝损伤的研究[J].中国乳品工业,2012,40(9):4-7.
[24]曾东,唐雨蕊,倪学勤,等.植物乳杆菌F22对肝脏和肠道微生物菌群的影响研究[J].营养学报,2010,32(4):370-374.
[2]ARAYA M,NUNEZ H,PAVEZ L,et al.Administration of high doses of Copper to capuchin monkeys does not cause liver damage but induces transcriptional activation of hepatic proliferative responses[J].The Journal of Nutrition,2012,142(2):233-237.
[3]田驰,黄夏梦,王霆.临床常用铜离子螯合剂药代动力学和不良反应研究进展[J].实用肝脏病杂志,2015(2):221-224.
[4]CHANG Y C,CHOI D,KIKUCHI S.Enhanced extraction of heavy metals in the two-step process with the mixed culture of Lactobacillus bulgaricus and Streptococcus thermophilus[J].Bioresource Technology,2012,103(1):477-480.
[5]MOSIER A P,BEHNKE J,JIN E T,et al.Microbial biofilms for the removal of Cu2+from CMP wastewater[J].Journal of Environmental Management,2015,160(67/72):67-72.
[6]SCHUT S,ZAUNER S,HAMPEL G,et al.Biosorption of Copper by wine-relevant lactobacilli[J].International Journal of Food Microbiology,2011,145(1):126-131.
[7]张晓黎,吴兴壮,张华.乳酸菌功能作用及其在生产中的应用[J].农业工程技术·农产品加工业,2015(5):36-39.
[8]靳克林.2011年濮阳市食品安全风险调查分析[J].河南预防医学杂志,2012,23(4):313-315.
[9]陈志,张婷,蒋芳,等.绵阳市食品中金属污染物监测结果分析[J].现代预防医学,2013,40(5):822-824.
[10]MILNE D B,NIELSEN F H.Effects of a diet low in Copper on copper-status indicators in postmenopausal women[J].The American Journal of Clinical Nutrition,1996,63(3):358-364.
[11]MILNE D B,DAVIS C D,NIELSEN F H.Low dietary Zinc alters indices of Copper function and status in postmenopausal women[J].Nutrition(Burbank,Los Angeles County,Calif.),2001,17(9):701-708.
[12]ZATTA P,DRAGO D,ZAMBENEDETTI P,et al.Accumulation of Copper and other metal ions and metallothioneinⅠ/Ⅱexpression in the bovine brain as a function of aging[J].Journal of Chemical Neuroanatomy,2008,36(1):1-5.
[13]SINGH M M,SINGH R,KHARE A,et al.Serum Copper in myocardial infarction--diagnostic and prognostic significance[J].Angiology,1985,36(8):504-510.
[14]KOK F J,VAN DUIJN C M,HOFMAN A,et al.Serum Copper and Zinc and the risk of death from cancer and cardiovascular disease[J].American Journal of Epidemiology,1988,128(2):352-359.
[15]SALONEN J T,SALONEN R,KORPELA H,et al.Serum Copper and the risk of acute myocardial infarction:aprospective population study in men in eastern Finland[J].American Journal of Epidemiology,1991,134(3):268-276.
[16]ZOWCZAK M,ISKRA M,PASZKOWSKI J,et al.Oxidase activity of ceruloplasmin and concentrations of Copper and Zinc in serum of cancer patients[J].Journal of Trace Elements in Medicine and Biology:Organ of the Society for Minerals and Trace Elements(GMS),2001,15(2/3):193-196.
[17]ODONOHUE J W,REID M A,VARGHESE A,et al.Micronodular cirrhosis and acute liver-failure due to chronic copper self-intoxication[J].European Journal of Gastroenterology&Hepatology,1993,5(7):561-562.
[18]ARAYA M,OLIVARES M,PIZARRO F,et al.Copper exposure and potential biomarkers of Copper metabolism[J].Biometals:an International Journal on the Role of Metal Ions in Biology,Biochemistry,and Medicine,2003,16(1):199-204.
[19]陈通克,管敏强,李翔,等.铜中毒对SD大鼠肝的影响研究[J].广东微量元素科学,2010,17(10):17-21.
[20]李万立,罗海吉,查龙应.铜过量小鼠肝损伤模型的建立及各项指标的观察研究[J].热带医学杂志,2008,8(12):1210-1212.
[21]万小华,罗小平.铜负荷大鼠肝脏FAS、FASL的表达及其意义[J].实用临床医学,2007,8(9):1-3.
[22]文彩虹.宜昌市土家族地区子宫颈癌筛查及其与微量元素的关系[D].广州:南方医科大学,2013.
[23]迟菲菲,田丰伟,王刚,等.植物乳杆菌LP1001缓解小鼠酒精性肝损伤的研究[J].中国乳品工业,2012,40(9):4-7.
[24]曾东,唐雨蕊,倪学勤,等.植物乳杆菌F22对肝脏和肠道微生物菌群的影响研究[J].营养学报,2010,32(4):370-374.