硫代乙酰胺诱导的A型肝性脑病小鼠焦虑样反应观察

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,P0.01)与穿梭次数(t=-2.656,P0.05);旷场实验的中央活动路程(t=-3.639,P0.05)、中央活动时间(t=-2.294,P0.05)、垂直运动次数(t=-2.282,P0.05)、理毛时间(t=5.992,P0.01);高架十字实验的开臂进入次数(t=-3.584,P0.05)、开臂滞留时间(t=-3.992,P0.05)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,P0.05)。且实验组小鼠血氨(t=-3.168,P0.05)、ALT(t=4.316,P0.05)、AST(t=-2.581,P0.05)、TBil(t=-9.127,P0.01)水平明显大于对照组,差异均有统计学意义。结论用TAA腹腔注射建立的A型肝性脑病小鼠模型有焦虑样反应;小剂量TAA诱导A型肝性脑病小鼠的焦虑样反应不伴有自发活动能力下降。     

大鼠肝性脑病模型的研究进展

肝性脑病是急慢性肝病较严重的并发症,死亡率很高,其发病机制尚未明确,防治也无特效疗法,因此对肝性脑病的基础和临床研究十分迫切.肝性脑病动物模型的建立对于发病机制、诊断和治疗的研究发挥着非常重要的作用,目前制备肝性脑病动物模型的动物种类较多,其中大鼠模型具有与人类相似性,良好的可重复性、可靠性、适用性、可控性、易行性和经济性等优势,应用最为广泛.本文就常用不同病因大鼠肝性脑病模型的制备方法和研究进展作简要综述.     

丁酸钠对肝性脑病大鼠血氨浓度的影响初探

目的：观察不同浓度丁酸钠对肝性脑病（HE）大鼠血氨浓度的影响以及对HE的防治效果。方法采用腹腔注射硫代乙酰胺（TAA）诱导急性肝性脑病模型。饲喂两周后造模两天,观察大鼠一般情况,并进行神经反射评级,血浆TBil、DBil、AST、ALT、血氨和肠道pH值等指标的测定。结果丁酸钠各组HE大鼠TBil、DBil、ALT、AST均有所下降,其中丁酸钠A组的肠道pH值较模型组差异有统计学意义（P ＜0.05）,丁酸钠A、B两组的血氨浓度较模型组明显降低（P均＜0.001）。丁酸钠处理可改善大鼠的神经反射,降低大鼠肝性脑病的分期。结论丁酸钠通过酸化肠道,降低HE大鼠的血氨浓度,进而改善HE大鼠所表现出来的精神症状。     

抗肝昏肠液对实验性肝性脑病大鼠模型IL—6的影响

目的：探讨抗肝昏肠液对肝性脑病大鼠白细胞介素6（IL－6）的影响。方法：采用药物诱导加结扎、切除2／3肝脏的方法建立大鼠肝性脑病模型,用抗肝昏肠液大、小剂量治疗的患者为治疗组,以乳果糖治疗的患者为对照组,观察药物对肝性脑病大鼠IL－6、脑电图、血氨、肝功能及肝组织病理学等的影响。结果：抗肝昏肠液大、小剂量对IL－6及其他指标都有不同程度的改善,大剂量组疗效优于乳果糖组。结论：抗肝昏肠液能显著降低IL－6含量。其影响可能与以下作用有关：（1）阻断肠道对氨、内毒素等有毒物质的吸收、促进其排除;（2）抑制单核巨噬细胞系统介导的细胞毒作用;（3）促进肝功能恢复,行使对内毒素等的清除功能。从而抑制IL－6对肝脏进一步的免疫损伤,促进肝性脑病的复苏。     

肝性脑病

症状性脑病源于多种病因,涉及各系统疾病,所以鉴别诊断就显得格外重要。只有确定诊断后“对症下药”,才能取得理想的疗效。本笔谈注重实用,望能对大家有所启迪。     

酒制大黄、乳酸菌素及复方乳黄制剂对急性肝性脑病大鼠防治的研究

目的探讨酒制大黄、乳酸菌素及其复方乳黄制剂对硫代乙酰胺(TAA)引起的大鼠急性肝性脑病的不同防治作用。方法用TAA灌胃建立大鼠急性肝性脑病模型,观察酒制大黄、乳酸菌素及其复方乳黄制剂对肝性脑病大鼠行为神经学、脑电图、肝功能、血氨浓度、血浆γ氨基丁酸(GABA)浓度和肝脏病理损伤的不同影响。结果乳黄制剂、酒制大黄、乳酸菌素均能不同程度地改善肝性脑病大鼠行为活动、神经反射和脑电图情况,恢复肝脏功能,降低肝性脑病级别、血氨和血浆GABA浓度,减轻肝脏病理损伤。其疗效大小依次为乳黄制剂>酒制大黄>乳酸菌素。结论酒制大黄与乳酸菌素有协同作用,两者组成的复方乳黄制剂对TAA引起的大鼠急性肝性脑病有显著防治作用。     

肝性脑病的治疗

肝性脑病 (hepaticencephalopathy ,HE)系严重肝病所致 ,是以代谢紊乱为主要特征的中枢神经系统功能失调的综合征 ;主要临床表现为意识障碍、行为异常及昏迷。以此将HE分为门体分流性脑病、急性脑病和慢性脑病三型。由于此概念在临床上存在一些问题 :(1)门体分流性脑病可见于伴     

肝性脑病的治疗近况

肝性脑病可由严重肝病或门一体分流(Portalsystemic encephalopath y,PSE)引起。其发病机理为:血脑屏障的结构与功能发生改变,以氨为主的多种毒性物质在血内沉积,氨基酸失平衡、假性神经递质及γ-氨基丁酸受体兴奋等。它常是由多个因素联合作用所致,治疗上应采用针对性的综合性措施,方能提高治疗成功率,降低病死率. 一、治疗原则氨对大脑有潜在毒性,它在肝内通过尿素合成而被解毒。严重肝病时尿素合成率明显减低,氨稳定性的维持由肝脏转向其它器官、组织,如肾及骨骼肌.在那里,氨被转化为谷氨酰胺及丙氨酸。晚期肝硬化患者有肌肉消瘦,肌肉对氨的摄取减少,同时蛋白质分解代谢旺盛,特别在伴有感染时.氨基酸     

肝性脑病的防治

肝性脑病的防治山东医科大学附属医院（２５００１２）赵宪，郭建强肝性脑病为肝脏疾病的主要死因之一，临床上主要采取综合治疗。１消除诱因急性病毒性、药物性或中毒性重症肝炎引起的急性或亚急性肝性脑病多无明显锈因，而因肝硬化和门脉高压症行门体分流术的患者，术后...     

Minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is the mildest form of spectrum of hepatic encephalopathy (HE). Patients with MHE have no recognizable clinical symptoms of HE but have mild cognitive and psychomotor deficits. The prevalence of MHE is high in patients with cirrhosis of liver and varies between 30% and 84%; it is higher in patients with poor liver function. The diagnostic criteria for MHE have not been standardized but rest on careful patient history and physical examination, normal mental status examination, demonstration of abnormalities in cognition and/or neurophysiological function, and exclusion of concomitant neurological disorders. MHE is associated with impaired health-related quality of life, predicts the development of overt HE and is associated with poor survival. Hence, screening all patients with cirrhosis for MHE using psychometric tests, and treatment of those patients diagnosed to have MHE has been recommended. Ammonia plays a key role in the pathogenesis of MHE, which is thought to be similar to that of overt HE. Thus, ammonia-lowering agents such as lactulose and probiotics have been tried. These agents have been shown to improve cognitive and psychometric deficits, and have good safety profile. Future studies will better define the role of other drugs, such as rifaximin, acetyl L-carnitine and L-ornithine L-aspartate.     

乳果糖治疗肝性脑病和亚临床肝性脑病149例临床观察

目的 进一步评估乳果糖对肝硬化肝性脑病和亚临床肝性脑病的疗效。方法 观察乳果糖治疗前后患者的精神状态、扑翼状震颤、脑电图、静脉血氨浓度和数字连接试验的改善情况。结果 乳果糖对肝性脑病组的脑病表现总有效率达96.5％,治疗前后静脉血氨浓度和数字连接试验的改善均有非常显著性差异(P<0.01);亚临床肝性脑病组治疗前后血氨有非常显著性差异(P<0.01),数字连接试验有显著性差异(P<0.05)。在乳果糖治疗观察期间,无一例亚临床肝性脑病患者发展为肝性脑病。结论 乳果糖适合于肝硬化肝性脑病和亚临床肝性脑病患者长期服用,可作为预防和治疗肝性脑病的常规用药。     

Minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy and can affect up to 80% of cirrhotic patients. By definition, it has no obvious clinical manifestation and is characterized by neurocognitive impairment in attention, vigilance and integrative function. Although often not considered to be clinically relevant and, therefore, not diagnosed or treated, MHE has been shown to affect daily functioning, quality of life, driving and overall mortality. The diagnosis of MHE has traditionally been achieved through neuropsychological examination, psychometric tests or the newer critical flicker frequency test. A new smartphone application (EncephalApp Stroop Test) may serve to function as a screening tool for patients requiring further testing. In addition to physician reporting and driving restrictions, medical treatment for MHE includes non-absorbable disaccharides (eg, lactulose), probiotics or rifaximin. Liver transplantation may not result in reversal of the cognitive deficits associated with MHE.     

Murine model to study brain,behavior and immunity during hepatic encephalopathy

AIM:To propose an alternative model of hepatic encephalopathy(HE) in mice,resembling the human features of the disease.METHODS:Mice received two consecutive intraperitoneal injections of thioacetamide(TAA) at low dosage(300 mg/kg).Liver injury was assessed by serum transaminase levels(ALT) and liver histology(hematoxylin and eosin).Neutrophil infiltration was estimated by confocal liver intravital microscopy.Coagulopathy was evaluated using prolonged prothrombin and partial thromboplastin time.Hemodynamic parameters were measured through tail cuff.Ammonia levels were quantified in serum and brain samples.Electroencephalography(EEG) and psychomotor activity score were performed to show brain function.Brain edema was evaluated using magnetic resonance imaging.RESULTS:Mice submitted to the TAA regime developed massive liver injury,as shown by elevation of serum ALT levels and a high degree of liver necrosis.An intense hepatic neutrophil accumulation occurred in response to TAA-induced liver injury.This led to mice mortality and weight loss,which was associated with severe coagulopathy.Furthermore,TAA-treated mice presented with increased serum and cerebral levels of ammonia,in parallel with alterations in EEG spectrum and discrete brain edema,as shown by magnetic resonance imaging.In agreement with this,neuropsychomotor abnormalities ensued 36 h after TAA,fulfilling several HE features observed in humans.In this context of liver injury and neurological dysfunction,we observed lung inflammation and alterations in blood pressure and heart rate that were indicative of multiple organ dysfunction syndrome.CONCLUSION:In summary,we describe a new murine model of hepatic encephalopathy comprising multiple features of the disease in humans,which may provide new insights for treatment.     

门冬氨酸鸟氨酸联合纳洛酮治疗急性肝性脑病的临床疗效观察

目的观察门冬氨酸鸟氨酸联合纳洛酮治疗急性肝性脑病的临床疗效。方法选取北京市第六医院2010年-2012年诊治的60例急性肝性脑病患者,随机分为门冬氨酸鸟氨酸治疗组(对照A组)15例、纳洛酮治疗组(对照B组)15例和门冬氨酸鸟氨酸联合纳洛酮治疗组(实验组)30例。各组均治疗7 d,对其治疗前后血氨浓度、肝功能(AST、TBIL)水平进行评价和比较,同时比较各组患者的临床疗效。结果治疗后对照A组和对照B组患者与实验组患者相比,其血氨及AST、TBIL水平差异均有统计学意义(P0.05),且实验组显效率及总有效率(63.33%,90.00%)明显高于对照组(33.33%,63.33%),差异具有统计学意义(P0.05)。结论门冬氨酸鸟氨酸联合纳洛酮治疗急性肝性脑病可以有效改善患者临床症状,提高临床疗效。     

Advances in cirrhosis: Optimizing the management of hepatic encephalopathy

Hepatic encephalopathy(HE) is a major complication of cirrhosis resulting in significant socioeconomic burden, morbidity, and mortality. HE can be further subdivided into covert HE(CHE) and overt HE(OHE). CHE is a subclinical, less severe manifestation of HE and requires psychometric testing for diagnosis. Due to the time consuming screening process and lack of standardized diagnostic criteria, CHE is frequently underdiagnosed despite its recognized role as a precursor to OHE. Screening for CHE with the availability of the Stroop test has provided a pragmatic method to promptly diagnose CHE. Management of acute OHE involves institution of lactulose, the preferred first-line therapy. In addition, prompt recognition and treatment of precipitating factors is critical as it may result in complete resolution of acute episodes of OHE. Treatment goals include improvement of daily functioning, evaluation for liver transplantation, and prevention of OHE recurrence. For secondary prophylaxis, intolerance to indefinite lactulose therapy may lead to non-adherence and has been identified as a precipitating factor for recurrent OHE. Rifaximin is an effective add-on therapy to lactulose for treatment and prevention of recurrent OHE. Recent studies have demonstrated comparable efficacy of probiotic therapy to lactulose use in both primary prophylaxis and secondary prophylaxis.     

Flumazenil does not affect the increase in rat hippocampal extracellular glutamate concentration produced during thioacetamide-induced hepatic encephalopathy

Hepatic encephalopathy (HE) is a neuropsychiatric disorder that often occurs as a consequence of acute or chronic liver failure. Previous reports have suggested that alterations in amino acid neurotransmission, particularly glutamate, may play an important role in the pathogenesis of HE. The objectives of the present study were to test the hypothesis that extracellular glutamate concentration is increased during HE, and to determine if flumazenil, a benzodiazepine antagonist, alters the extracellular concentration of glutamate during HE. The experimental approach involved using microdialysis probes to measure rat hippocampal extracellular glutamate concentration. HE was brought about as a result of thioacetamide-induced liver failure. Thioacetamide produced behavioral and metabolic effects, such as somnolence, hyperventilation and hyperammonemia, consistent with stage three HE. Comparison with saline-treated rats demonstrated that HE was associated with a significant increase (p=0.010) in extracellular hippocampal glutamate concentration. Administration of flumazenil caused a transient increase in arousal level, but did not affect the increase in glutamate concentration (p=0.93). These results corroborate the theory that glutamate neurotransmission is altered during HE and suggest that the flumazenil arousal of HE rats is not mediated by a change in extracellular glutamate concentration.     

Evidence against a role for endotoxin in the hepatic encephalopathy of rats with thioacetamide-induced fulminant hepatic failure

BACKGROUND AND AIMS: Endotoxin has been proposed to participate in the development of hepatic encephalopathy. However, there is no published data concerning the effects of endotoxin neutralization on the degree of hepatic encephalopathy. The present study investigated the effect of chronic intraperitoneal injection of polymyxin B, a neutralizing antagonist of endotoxin, on hepatic encephalopathy in rats with thioacetamide (TAA)-induced fulminant hepatic failure. METHODS: Male Sprague-Dawley rats weighing 300-350 g were used. Fulminant hepatic failure was induced by intraperitoneal injection of TAA (350 mg/kg/day) for 3 days. Two series of rats were designed to compare the effects of low dose (0.1 mg) or high dose (0.2 mg) intraperitoneal polymyxin B administration versus normal saline (NS) on hepatic encephalopathy. The injection was twice daily started from 2 days prior to TAA administration and lasted for 5 days. Severity of encephalopathy was assessed by the counts of motor activity in an Opto-Varimex animal activity meter. Plasma levels of endotoxin and tumor necrosis factor-alpha (an index of liver injury) were measured by Limulus assay and the ELISA method, respectively. RESULTS: Neutralization of endotoxin by either low dose or high dose polymyxin B administration did not significantly alleviate the degree of hepatic encephalopathy, as represented by the counts of motor activities (P > 0.05). Plasma levels of endotoxin and tumor necrosis factor-alpha were comparable between rats treated with polymyxin B or NS (P > 0.05). CONCLUSION: Our findings do not support the notion that endotoxin plays a major role in the pathogenesis of hepatic encephalopathy in rats with TAA-induced fulminant hepatic failure.