[1]赵夏浦,姚志军,涂婉玉,等.去甲肾上腺素转运体和多巴胺转运体在甲基苯丙胺成瘾致大鼠心肌损伤中的作用及机制[J].新乡医学院学报,2022,39(9):806-809.[doi:10.7683/xxyxyxb.2022.09.002]
　ZHAO Xiapu,YAO Zhijun,TU Wanyu,et al.Effect and mechanism of norepinephrine transporter and dopamine transporter in myocardial injury induced by methamphetamine addiction in rats[J].Journal of Xinxiang Medical University,2022,39(9):806-809.[doi:10.7683/xxyxyxb.2022.09.002]
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去甲肾上腺素转运体和多巴胺转运体在甲基苯丙胺成瘾致大鼠心肌损伤中的作用及机制
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
39
期数:
2022年9
页码:
806-809
栏目:
基础研究
出版日期:
2022-09-05

文章信息/Info

Title:
Effect and mechanism of norepinephrine transporter and dopamine transporter in myocardial injury induced by methamphetamine addiction in rats
作者:
赵夏浦1; 姚志军2; 涂婉玉2; 董　磊3; 张腾腾2; 刘　奔2; 任明芬1
(1.新乡医学院第二附属医院，河南　新乡　453002；2.新乡医学院法医学院新乡市法医毒理学重点实验室，河南　新乡　453003；3.新乡医学院基础医学院/河南省医用组织再生重点实验室，河南　新乡　453003)
Author(s):
ZHAO Xiapu1; YAO Zhijun2; TU Wanyu2; DONG Lei3; ZHANG Tengteng2; LIU Ben2; REN Mingfen1
(1.The Second Affiliated Hospital of Xinxiang Medical University,Xinxiang 453002,Henan Province,China;2.Xinxiang Key Laboratory of Forensic Toxicology，School of Forensic Medicine，Xinxiang Medical University，Xinxiang 453003，Henan Province，China;3.Henan Key Laboratory of Medical Tissue Regeneration,School of Basic Medical Sciences,Xinxiang Medical University,Xinxiang 453003,Henan Province,China)
关键词:
甲基苯丙胺; 心肌; 去甲肾上腺素转运体; 多巴胺转运体; 条件性位置偏爱
Keywords:
methamphetamine; myocardium; norepinephrine transporter; dopamine transporter; conditioned place preference
分类号:
R541
DOI:
10.7683/xxyxyxb.2022.09.002
文献标志码:
A
摘要:
目的　探讨去甲肾上腺素转运体（NET）和多巴胺转运体（DAT）在甲基苯丙胺（MA）成瘾致大鼠心肌损伤中的作用及机制。方法　将17只雄性8周龄Sprague Dawley大鼠随机分为对照组（n=7）和MA组（n=10）。MA组大鼠分别于实验第 5、7、9、11、13、15、17天腹腔注射5 g·L-1 MA溶液（1 mL·kg-1），第6、8、10、12、14、16、18天腹腔注射生理盐水（1 mL·kg-1）；对照组大鼠每日腹腔注射生理盐水（1 mL·kg-1）。实验第19天，对2组大鼠进行条件性位置偏爱测试，记录大鼠在白箱中停留时间和活动轨迹，分析活动轨迹曲线密度。2组大鼠用体积分数2 %的戊巴比妥钠进行麻醉，依次用200 mL生理盐水和200 mL多聚甲醛溶液（4 g·L-1）行心脏灌流，然后取左心室制作组织切片，采用苏木精-伊红染色观察2组大鼠左心室心肌组织形态学变化，免疫组织化学法检测2组大鼠心肌组织中NET及DAT表达。结果　实验第19天，对照组和MA组大鼠白箱中停留时间分别为（404.478±87.512）、（165.433±27.323）s，MA组大鼠白箱中停留时间显著长于对照组（P<0.05）；MA组大鼠白箱活动轨迹曲线密度明显高于前测期，对照组大鼠白箱活动轨迹曲线密度无明显变化。对照组大鼠左心室心肌细胞排列整齐，未见心肌损伤表现；MA组大鼠左心室心肌细胞排列紊乱，可见心肌组织出血、心肌细胞波纹样改变，心肌内炎症细胞聚集。对照组和MA组大鼠心肌组织中均有NET及DAT表达，MA组大鼠心肌组织中NET及DAT相对表达量显著低于对照组（P<0.05）。结论　MA成瘾可对大鼠心肌产生毒性作用，其机制可能是通过降低心肌组织中NET和DAT表达水平来增加突触后儿茶酚胺水平，从而导致心肌损伤。
Abstract:
Objective　To investigate the effect and mechanism of norepinephrine transporter (NET) and dopamine transporter (DAT) in methamphetamine (MA) addiction-induced myocardial injury in rats.Methods　Seventeen male 8-week-old Sprague Dawley rats were randomly divided into control group (n=7) and MA group (n=10).The rats in the MA group were injected intraperitoneally with 5 g·L-1MA solution (1 mL·kg-1) on the 5th,7th,9th,11th,13th,15th,17th day,and saline (1 mL·kg-1) on the 6th,8th,10th,12th,14th,16th and 18th day;the rats in the control group were injected intraperitoneally with saline (1 mL·kg-1) daily.On the 19th day of the experiment,the conditioned place preference test were performed in the rats of the two groups,and the residence time and activity track of rats in the white box were recorded,the curve density of movement track was analyzed.The rats in the two groups were anesthetized with volume fraction of 2% sodium pentobarbital,the heart was perfused with 200 mL normal saline and 200 mL paraformaldehyde solution (4 g·L-1) successively,and then the left ventricle was taken out and made into tissue sections;the morphological changes of left ventricle of rats in the two groups were observed by hematoxylin eosin staining,and the expressions of NET and DAT in the myocardial tissue of rats in the two groups were detected by immunohistochemistry.Results　On the 19th day of the experiment,the residence time in the white box of rats in the control group and MA group was (404.478±87.512) s and (165.433±27.323) s,respectively;the residence time in the white box of rats in the MA group was significantly longer than that in the control group (P<0.05).The curve density of movement track in the white box of rats in the MA group after administration was significantly higher than that in the pre-test period,while there was no significant change in curve density of movement track in the white box of rats in the control group.In the control group,the myocardial cells in the left ventricle were neatly arranged and no myocardial injury was observed;in the MA group,the myocardial cells in the left ventricle of rats were disordered,and the myocardial tissue hemorrhage,ripple-like changes in myocardial cells and inflammatory cell aggregation were observed.NET and DAT were expressed in the myocardial tissues of rats in the control group and MA group,while the relative expression levels of NET and DAT in the myocardial tissues of rats in the MA group were significantly lower than those in the control group (P<0.05).Conclusion　MA addiction can produce toxic effects on myocardium of rat,and its mechanism may be to increase the level of postsynaptic catecholamine by reducing the expression levels of NET and DAT in myocardial tissue.

参考文献/References:

［1］　ABBRUSCATO T J,TRIPPIER P C.DARK classics in chemical neuroscience:methamphetamine［J］.ACS Chem Neurosci,2018,9(10):2373-2378.
［2］　MIZOGUCHI H,YAMADA K.Methamphetamine use causes cognitive impairment and altered decision-making［J］.Neurochem Int,2019,124:106-113.
［3］　PAPAGEORGIOU M,RAZA A,FRASER S,et al.Methamphetamine and its immune-modulating effects［J］.Maturitas,2019,121:13-21.
［4］　朱婷娜,刘鹏亮,董文娟,等.不同剂量天麻素对甲基苯丙胺依赖大鼠条件位置偏爱及海马小胶质细胞激活的影响［J］.昆明医科大学学报,2021,42(5):6-11.
ZHU T N,LIU P L,DONG W J,et al.Effects of different doses of gastrodin on conditioned place preference and microglia activation in hippocampus of methamphetamine dependent rats［J］.J Kunming Med Univ,2021,42(5):6-11.
［5］　WANG Z Y,GUO L K,HAN X,et al.Naltrexone attenuates methamphetamine-induced behavioral sensitization and conditioned place preference in mice［J］.Behav Brain Res,2021,399:112971.
［6］　ZHAO Z,KIM Y W,YANG Y,et al.Glycyrrhizae radix methanol extract attenuates methamphetamine-induced locomotor sensitization and conditioned place preference［J］.Evid Based Complement Alternat Med,2014,2014:152063.
［7］　OGEIL R P,ARUNOGIRI S,GRIGG J.Methamphetamine addiction:do biological rhythms matter,and could they play a role in treatment［J］.Sleep,2021,44(7):zsab052.
［8］　余家凤,赵鑫,刘映峰,等.甲基苯丙胺相关心血管疾病的研究进展［J］.临床心血管病杂志,2021,37(3):200-203.
YU J F,ZHAO X,LIU Y F,et al.Research progress in methamphetamine-related cardiovascular disease［J］.J Clin Cardiol,2021,37(3):200-203.
［9］　BEN-YEHUDA O,SIECKE N，CRYSTA L.Methamphetamine:adrug and cardiovascular epidemic［J］.JACC Heart Fail,2018,6(3):219-221.
［10］　AKHGARI M,MOBARAKI H,ETEMADI-ALEAGHA A.Histopathological study of cardiac lesions in methamphetamine poisoning-related deaths［J］.Daru,2017,25(1):5.
［11］　翟真,金华.甲基苯丙胺相关性心肌病［J］.中国循证心血管医学杂志,2017,9(9):1145-1146.
ZHAI Z,JIN H.Methamphetamine-related cardiomyopathy［J］.Chin J Evid-Based Cardiovasc Med,2017,9(9):1145-1146.
［12］　NEWMAN A H,KU T,JORDAN C J,et al.New drugs,old targets:tweaking the dopamine system to treat psychostimulant use disorders［J］.Annu Rev Pharmacol Toxicol,2021,61:609-628.
［13］　FREELING J L,MCFADDEN L M.The emergence of cardiac changes following the self-administration of methamphetamine［J］.Drug Alcohol Depend,2020,212:108029.
［14］　GRAL I,ATKA K,BAJDA M.Structure modeling of the norepinephrine transporter［J］.Biomolecules,2020,10(1):102.
［15］　KEVIL C G,GOEDERS N E,WOOLARD M D,et al.Methamphetamine use and cardiovascular disease［J］.Arterioscler Thromb Vasc Biol,2019,39(9):1739-1746.
［16］　CHEN M,ZHANG Y,WANG H,et al.Inhibition of the norepinephrine transporter rescues vascular hyporeactivity to catecholamine in obstructive jaundice［J］.Eur J Pharmacol,2021,900:174055.
［17］　CAO L L,MARSHALL J M,FABRITZ L,et al.Resting cardiac sympathetic firing frequencies suppress terminal norepinephrine transporter uptake［J］.Auton Neurosci,2021,232:102794.
［18］　CHALLASIVAKANAKA S,ZHEN J,SMITH M E,et al.Dopamine transporter phosphorylation site threonine 53 is stimulated by amphetamines and regulates dopamine transport,efflux,and cocaine analog binding［J］.J Biol Chem,2017,292(46):19066-19075.
［19］　JAYARAMAYYA K,IYER M,VENKATESAN D,et al.Unraveling correlative roles of dopamine transporter (DAT) and parkin in Parkinson′s disease (PD):a road to discovery［J］.Brain Res Bull,2020,157:169-179.
［20］　MARSHALL C A,BRODNIK Z D,MORTENSE O V,et al.Selective activation of dopamine D3 receptors and norepinephrine transporter blockade enhances sustained attention［J］.Neuropharmacology,2019,148:178-188.
［21］　LATIF A,AHSAN M J,LATEEF N,et al.Is Methamphetamine-linked cardiomyopathy an emerging epidemic for new generation?［J］.Curr Probl Cardiol,2021,Epub ahead of print.DOI:10.1016/j.cpcardiol.2021.101042.
［22］　MARAUES F Z,EIKELIS N,BAYLES R G,et al.A polymorphism in the norepinephrine transporter gene is associated with affective and cardiovascular disease through a microRNA mechanism［J］.Mol Psychiatry,2017,22(1):134-141.
［23］　SCHWARZBACH V,LENK K,LAUFS U.Methamphetamine-related cardiovascular diseases［J］.ESC Heart Fail,2020,7(2):407-414.

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更新日期/Last Update: 2022-09-05