海洛因对仔鼠肝相关活性物质的影响
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摘要
为探讨海洛因对肝功能的影响,选60只昆明小鼠(仔鼠)用递增剂量在第1～5 d,6～10 d和11～15 d分别腹腔连续注射2,3和4 g·L~(-1)的海洛因溶液0.2 mL,称量仔鼠体重和肝重的变化,用比色法检测仔鼠血浆γ-谷氨酰转肽酶(γ-GT)、碱性磷酸酶(AKP)活性及肝组织髓过氧化物酶(MPO)活性的变化,用免疫化学法检测肝组织Survivin蛋白表达的变化.结果显示,与对照组比较,海洛因组仔鼠的体重、肝重明显降低,血浆γ-GT,AKP活性显著升高,肝组织MPO活性升高,Survivin蛋白表达量明显升高(P<0.05或P<0.01).表明海洛因影响仔鼠的肝功能,对肝组织有损伤效应,而肝组织可通过表达Survivin蛋白调控细胞的凋亡.
To investigate the effect of heroin on liver function,60 filial mice are intraperitoneal injected escalation doses(2,3 and 4 g·L~(-1))of herion(0.2 mL) at(1～5 d,6～10 d,11～15 d).Changes in body weight and liver weight of the mice are measured.The changes of plasma gamma-glutamyltransferase(γ-GT),alkaline phosphatase(AKP) activity and liver myeloperoxidase(MPO) activity in filial mice are determined by colorimetry.The expression of Survivin protein in liver tissue are detected by immunochemistry.The results show that compared with the control group,the body weight and liver weight of the heroin group are significantly reduced,the activity of serum γ-GT and AKP are increased significantly,and the activity of MPO in liver tissue are increased,the expression level of Survivin protein are increased significantly(P<0.05 or P<0.01).These suggest that heroin can affect the liver function of filial mice and has a damaging effect on liver tissue which can regulate cell apoptosis by expressing Survivin protein.
To investigate the effect of heroin on liver function,60 filial mice are intraperitoneal injected escalation doses(2,3 and 4 g·L~(-1))of herion(0.2 mL) at(1～5 d,6～10 d,11～15 d).Changes in body weight and liver weight of the mice are measured.The changes of plasma gamma-glutamyltransferase(γ-GT),alkaline phosphatase(AKP) activity and liver myeloperoxidase(MPO) activity in filial mice are determined by colorimetry.The expression of Survivin protein in liver tissue are detected by immunochemistry.The results show that compared with the control group,the body weight and liver weight of the heroin group are significantly reduced,the activity of serum γ-GT and AKP are increased significantly,and the activity of MPO in liver tissue are increased,the expression level of Survivin protein are increased significantly(P<0.05 or P<0.01).These suggest that heroin can affect the liver function of filial mice and has a damaging effect on liver tissue which can regulate cell apoptosis by expressing Survivin protein.
引文
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[2] 何军,田洪伦,张姝,等.海洛因依赖者9项生化指标检测分析[J].贵州医药,2011,35(7):645.
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[15] 孟茹,李重阳,俞诗源,等.当归(粗)多糖对麻黄素肝组织损伤的保护作用[J].解剖学报,2015,46(3):379.
[16] 吕娟涛,汤浩.女贞子多糖对肝损伤保护作用的实验研究[J].中国医院药学杂志,2010,30(12):1024.
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[19] DENG X,WU K,WAN J,et a1.Aminotriazole attenuated carbon tetrachloride-induced oxidative liver injury in mice[J].Food Chem Toxicol,2012,50(9):3073.
[20] 陈新瑜,李小清,况舸,等.退黄合剂对ANIT致胆汁淤积性肝损伤的保护作用及机制研究[J].中国中医急症,2014,23(9):1614.
[21] GUO F,NIMMANAPALLI R,PARANAWITHANA S,et al.Ectopic overexpression of second mitochondria-derived activator of caspases(Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothilone B derivative-(BMS247550) and Apo-2L/TRAIL-induced apoptosis[J].Blood,2002,99(9):3419.
[22] MESRI M,WALL N R,LI J,et al.Cancer gene therapy using a survivin mutant adenovirus[J].J Clin Invest,2001,108(7):981.
[23] SHIN S,SUNG B J,CHO Y S,et a1.An anti-apoptotic protein human Survivin is a direct inhibitor of Caspase-3 and-7[J].Biochemistry,2001,40(4):1117.
[24] ZHANG C,CAO X,GEI Y,et al.Silencing of survivin by YM155 induces apoptosis and growth arrest in hepatocellular carcinoma cells[J].Oncol Lett,2015,10(3):1627.
[25] COUMAR M S,TSAI F Y,KANWAR J R,et al.Treat cancers by targeting Suevivin:just adream or future reality[J].Cancer Treat Rev,2013,39(7):802.
[26] VERHAGEN A M,EKERT P G,PAKUSCH M,et a1.Identification of DIABLO,a mammalian protein that promotes apoptosis by binding to and antagonizing lAP proteins[J].Cell,2000,102(1):43.
[27] 高峰.Survivin在微囊化肝细胞移植治疗暴发性肝衰竭大鼠肝组织中的动态变化[D].温州:温州医科大学,2007.
[28] 李丰.Survivin和Livin在肝细胞癌中的表达及分析研究[D].广州:广州医科大学,2013.
[2] 何军,田洪伦,张姝,等.海洛因依赖者9项生化指标检测分析[J].贵州医药,2011,35(7):645.
[3] WILLIAN M,LEE M D.Drug-induced hepatotoxicity[J].N Engl J Med,2003,349(5):474.
[4] 黄仕美,臧贵勇,王杰,等.吸食海洛因死亡60例法医学分析[J].贵阳医学院学报,2013,38(2):203.
[5] SUK K T,KIM D J.Drug-induced liver injury:presennt and future[J].Clin Mol Hepatol,2012,18(3):249.
[6] 俞诗源,何玲慧,朱嘉宁,等.孕鼠注射海洛因对仔鼠小脑组织和抗氧化物酶活性的影响[J].西北师范大学学报(自然科学版),2018,54(5):63.
[7] 肖世南,俞诗源.麻黄素对仔鼠睾丸组织结构和Bax、EGF蛋白的影响[J].动物学杂志,2013,48(4):634.
[8] SEHGAL N,SMITH H S,MANCHIKANTI L.Peripherally acting opioids and clinical implications for pain control[J].Pain Physician,2011,14(3):249.
[9] 万苹.海洛因成瘾者体表胃电研究[A]// 中华医学会.中华医学会2001年全国胃电图和胃肠动力研讨会论文摘要集.中华医学会:中华医学会,2001:1.
[10] 俞诗源,王悦,郭婷婷,等.海洛因对母鼠体重、行为及肺中相关活性物质表达的影响[J].西北师范大学学报(自然科学版),2010,46(2):94.
[11] 孙志强,毛远丽.肝病酶学指标及临床应用进展[J].中华检验医学杂志,2005,28(6):659.
[12] BULUSU S,SHARMA M.What does serum γ-glutamyltransferase tell us as a cardiometabolic risk marker?[J].Ann Clin Biochem,2016,53(3):312.
[13] WHITFIELD J B.Gamma glutamyl transferase[J].Crit Rev Clin Lab Sci,2001,38(4):263.
[14] 刘建国,高辉,于俊玲,等.双环醇对抗精神病药物所致肝损伤患者血清碱性磷酸酶(ALP)及白蛋白(ALB)水平的影响[J].中国实验诊断学,2015,19(1):59.
[15] 孟茹,李重阳,俞诗源,等.当归(粗)多糖对麻黄素肝组织损伤的保护作用[J].解剖学报,2015,46(3):379.
[16] 吕娟涛,汤浩.女贞子多糖对肝损伤保护作用的实验研究[J].中国医院药学杂志,2010,30(12):1024.
[17] BAINTON D F,FARQUHAR M G.Differences in enzyme content of azurophil and specific granules of polymorphonuclear leukocytes.II.Cytochemistry and electron microscopy of bone marrow cells[J].J Cell Biol,1968,39(2):299.
[18] 韩莉莉,沈晓丽.髓过氧化物酶及其基因多态性的研究进展[J].医学综述,2007,13(17):1288.
[19] DENG X,WU K,WAN J,et a1.Aminotriazole attenuated carbon tetrachloride-induced oxidative liver injury in mice[J].Food Chem Toxicol,2012,50(9):3073.
[20] 陈新瑜,李小清,况舸,等.退黄合剂对ANIT致胆汁淤积性肝损伤的保护作用及机制研究[J].中国中医急症,2014,23(9):1614.
[21] GUO F,NIMMANAPALLI R,PARANAWITHANA S,et al.Ectopic overexpression of second mitochondria-derived activator of caspases(Smac/DIABLO) or cotreatment with N-terminus of Smac/DIABLO peptide potentiates epothilone B derivative-(BMS247550) and Apo-2L/TRAIL-induced apoptosis[J].Blood,2002,99(9):3419.
[22] MESRI M,WALL N R,LI J,et al.Cancer gene therapy using a survivin mutant adenovirus[J].J Clin Invest,2001,108(7):981.
[23] SHIN S,SUNG B J,CHO Y S,et a1.An anti-apoptotic protein human Survivin is a direct inhibitor of Caspase-3 and-7[J].Biochemistry,2001,40(4):1117.
[24] ZHANG C,CAO X,GEI Y,et al.Silencing of survivin by YM155 induces apoptosis and growth arrest in hepatocellular carcinoma cells[J].Oncol Lett,2015,10(3):1627.
[25] COUMAR M S,TSAI F Y,KANWAR J R,et al.Treat cancers by targeting Suevivin:just adream or future reality[J].Cancer Treat Rev,2013,39(7):802.
[26] VERHAGEN A M,EKERT P G,PAKUSCH M,et a1.Identification of DIABLO,a mammalian protein that promotes apoptosis by binding to and antagonizing lAP proteins[J].Cell,2000,102(1):43.
[27] 高峰.Survivin在微囊化肝细胞移植治疗暴发性肝衰竭大鼠肝组织中的动态变化[D].温州:温州医科大学,2007.
[28] 李丰.Survivin和Livin在肝细胞癌中的表达及分析研究[D].广州:广州医科大学,2013.
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