Anxiety in mice with acute hepatic encephalopathy induced by thioacetamide
-
摘要:
目的探讨硫代乙酰胺(TAA)诱导的A型肝性脑病小鼠的精神障碍。方法 30只雄性昆明种小鼠随机分为实验组15只,对照组15只。实验组采用TAA 200 mg·kg-1·d-1,连续腹腔注射3 d至累积计量到600 mg/kg,正常对照组腹腔注射生理盐水,造模24 h后进行脑功能评分、明暗箱、旷场及高架十字实验。行为学检测结束后24 h行血氨及肝脏生化指标检测。两组间比较采用独立样本t检验。结果实验组小鼠在明暗箱实验中的明箱滞留时间(t=-4.006,P<0.01)与穿梭次数(t=-2.656,P<0.05);旷场实验的中央活动路程(t=-3.639,P<0.05)、中央活动时间(t=-2.294,P<0.05)、垂直运动次数(t=-2.282,P<0.05)、理毛时间(t=5.992,P<0.01);高架十字实验的开臂进入次数(t=-3.584,P<0.05)、开臂滞留时间(t=-3.992,P<0.05)与对照组小鼠相比,差异均具有统计学意义。但旷场实验中两组小鼠活动总路程差异无统计学意义(t=-0.96,p>0.05)。且实验组小...
Abstract:Objective To evaluate the mental disorders in mice with thioacetamide ( TAA) -induced acute hepatic encephalopathy ( AHE) .Methods Thirty male Kunming mice were equally and randomly divided into two groups ( treatment group and control group) . Mice in the treatment group received an intraperitoneal injection of TAA ( 200 mg·kg-1·d-1for 3 days, up to 600 mg·kg-1) , as compared with the same volume of physiological saline in the control group. Neurological function score, light /dark box, open field, and elevated plus-maze test were used to determine behavioral parameters at 24 h after the model was established. Serum ammonia, aspartate amino transferase ( AST) , alanine aminotransferase ( ALT) , and total bilirubin ( TBil) were measured at 24 h post determination of behavioral parameters. Comparison between two groups was made by independent-samples t test. Results In the light /dark box test, the treatment group had significantly reduced residence time in the light box and number of shuttles between two boxes ( t =-4. 006, P < 0. 01; t =-2. 656, P < 0. 05) ; in the open field test, the treatment group had significantly reduced central distance, central time, and number of vertical movements ( t =-3. 639, P < 0. 05;t =-2. 294, P < 0. 05; t =-2. 282, P < 0. 05) , as well as increased grooming time ( t = 5. 992, P < 0. 01) ; meanwhile, the number of open-arm entries and residence time in the open arm for the treatment group were also reduced in the elevated plus-maze test, as compared with the control group ( t =-3. 584, P < 0. 05; t =-3. 992, P < 0. 05) . However, the total distance in the open field test showed no significant difference between the two groups ( t =-0. 96, P > 0. 05) . Moreover, compared with the control group, the treatment group had significantly higher levels of serum ammonia ( t =-3. 168, P < 0. 05) , ALT ( t = 4. 316, P < 0. 05) , AST ( t =-2. 581, P < 0. 05) , and TBil ( t =-9. 127, P < 0. 01) . Conclusion Mice with AHE induced by an intraperitoneal injection of low-dose TAA have anxiety-related behaviors; the anxiety-related behaviors are not associated with reduced locomotor activities.
-
Key words:
- hepatic encephalopathy /
- anxiety /
- thioacetamide
-
[1]LES I, DOVAL E, FLAVIM, et al.Quality of life in cirrhosis is related to potentially treatable factors[J].Eur J Gastroenterol Hepatol, 2010, 22 (2) :221-227. [2]NARDELLI S, PENTASSUGLIO I, PASQUALE C, et al.Depression, anxiety and alexithymia symptoms are major determinants of health related quality of life (HRQoL) in cirrhotic patients[J].Metab Brain Dis, 2013, 28 (2) :239-243. [3]ROEST AM, THOMBS BD, GRACE SL, et al.Somatic/affective symptoms, but not cognitive/affective symptoms, of depression after acute coronary syndrome are associated with 12-month all-cause mortality[J].J Affect Disord, 2011, 131 (1-3) :158-163. [4]KAUHANEN J, KAPLAN G, COHEN R, et al.Alexithymia and risk of death in middle-aged men[J].J Psychosom Res, 1996, 41 (6) :541-549. [5]JIANG H, XIE Q.Advances in the diagnosis and treatment of hepatic encephalopathy[J].J Clin Hepatol, 2011, 27 (10) :1027-1031. (in Chinese) 姜浩, 谢青.肝性脑病临床诊治的进展[J].临床肝胆病杂志, 2011, 27 (10) :1027-1031. [6]FERENCI P, LOCKWOOD A, MULLEN K, et al.Hepatic encephalopathy-definition, nomenclature, diagnosis, and quantification:final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998[J].Hepatology, 2002, 35 (3) :716-721. [7]BUTTERWORTH RF, NORENBERG MD, FELIPO V, et al.Experimental models of hepatic encephalopathy:ISHEN guidelines[J].Liver Int, 2009, 29 (6) :783-788. [8]MIRANDA AS, RODRIGUES DH, VIEIRA LB, et al.A thioacetamide-induced hepatic encephalopathy model in C57BL/6 mice:a behavioral and neurochemical study[J].Arq Neuropsiquiatr, 2010, 68 (4) :597-602. [9]AVRAHAM Y, GRIGORIADIS N, POUTAHIDIS T, et al.Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice[J].Br J Pharmacol, 2011, 162 (7) :1650-1658. [10]LI X, RISBROUGH VB, CATES-GATTO C, et al.Comparison of the effects of the GABAB receptor positive modulator BHF177 and the GABAB receptor agonist baclofen on anxiety-like behavior, learning, and memory in mice[J].Neuropharmacology, 2013, 70 (2) :156-167. [11]CAROLA V, D'OLIMPIO F, BRUNAMONTI E, et al.Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice[J].Behav Brain Res, 2002, 134 (1-2) :49-57. [12]LAU AA, CRAWLEY AC, HOPWOOD JJ, et al.Open field locomotor activity and anxiety-related behaviors in mucopolysaccharidosis type IIIA mice[J].Behav Brain Res, 2008, 191 (1) :130-136. [13]NEWMAN MG, LLERA SJ, ERICKSON TM, et al.Worry and generalized anxiety disorder:a review and theoretical synthesis of evidence on nature, etiology, mechanisms, and treatment[J].Annu Revi Clin Psychol, 2013, 9:275-297. [14]RUSCIO A, CHIU W, ROY-BYRNE P, et al.Broadening the definition of generalized anxiety disorder:effects on prevalence and associations with other disorders in the National Comorbidity Survey Replication[J].J Anxiety Disord, 2007, 21 (5) :662-676. [15]GRANT B, HASIN D, STINSON F, et al.Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder in the USA:results from the National Epidemiologic Survey on Alcohol and Related Conditions[J].Psychol Med, 2005, 35 (12) :1747-1759. [16]SCHIENLE A, HETTEMA JM, CCEDA R, et al.Neurobiology and genetics of generalized anxiety disorder[J].Psychiatr Ann, 2011, 41 (2) :113-123. [17]YASSA M, HAZLETT R, STARK C, et al.Functional MRI of the amygdala and bed nucleus of the stria terminalis during conditions of uncertainty in generalized anxiety disorder[J].J Psychiatr Res, 2012, 46 (8) :1045-1052. [18]HERDEN C, BEINEKE A, HETZEL U, et al.Unusual manifestation of hepatic encephalopathy in two Irish wolfhound siblings[J].Vet Rec, 2003, 153 (22) :682-686. [19]CAULI O, LLANSOLA M, ERCEG S, et al.Hypolocomotion in rats with chronic liver failure is due to increased glutamate and activation of metabotropic glutamate receptors in substantia nigra[J].J Hepatol, 2006, 45 (5) :654-661. [20]SERGEEVA OA, SCHULZ D, DOREULEE N, et al.Deficits in cortico-striatal synaptic plasticity and behavioral habituation in rats with portacaval anastomosis[J].Neuroscience, 2005, 134 (4) :1091-1098. [21]LEKE R, BAK L, IVERSEN P, et al.Synthesis of neurotransmitter GABA via the neuronal tricarboxylic acid cycle is elevated in rats with liver cirrhosis consistent with a high GABAergic tone in chronic hepatic encephalopathy[J].J Neurochem, 2011, 117 (5) :824-832. [22]WESIERSKA M, KLINOWSKA HD, ADAMSKA I, et al.Cognitive flexibility but not cognitive coordination is affected in rats with toxic liver failure[J].Behav Brain Res, 2006, 171 (1) :70-77.
计量
- 文章访问数: 2916
- HTML全文浏览量: 34
- PDF下载量: 545
- 被引次数: 0