CCl1肝硬变模型大鼠血清氨基酸变化及其意义

作者应用CCl1高脂低蛋白复合因素制造大鼠肝硬变模型，测定大鼠血氨基酸水平。结果表明：支链氨基酸（BCAA）水平明显降低，而芳香族氨基酸（AAA）明显增高，BCAA／AAA比值显著增高。这些变化与临床肝硬变患者的变化相一致，因此该模型对研究肝硬变时氨基酸失衡的机制，以及筛选临床上行之有效的治疗肝硬变的药物，均有良好的价值。     

慢性肝病患者血浆氨基酸模式改变及其临床意义的再探讨

本研究分析91例慢性肝病患者血浆氨基酸水平与肝功能损害的关系。慢性肝炎和按child-pugh计分标准进行肝功能分级的肝硬变患者．其血浆支链氨基酸(BCAA)与芳香氨基酸(AAA)克分子浓度比值(BCAA／AAA)有显著统计学差异。病情稳定的慢性肝炎患者，其BCAA／AAA均大于2．5(n=14)；肝功能A级的肝硬变患者，其比值多数>2．5．有25．6%病例小于2.5(n=39);肝功能B级的肝硬变患者全部病例小于2．5(n=32)．有9．4％病例小于1.0;肝功能C级的肝硬变患者全部病例小于2．5(n=6)，有50％病例小于1．0。上述情况提示BCAA／AAA可怍为慢性肝病患者肝功能改变的一项较敏感和可靠的量化监测指标。     

胎肝细胞输注治疗后血浆氨基酸的变化及其与肝功能的关系

本文观察了肝硬化患者输注胎肝细胞后血浆氨基酸和肝功能的变化。治疗组血浆BCAA浓度显著增高,AAA和BCAA/AAA变化不明显;对照组BCAA和AAA均无明显变化。输注后,AAA仍与白蛋白呈负相关,与球蛋白呈正相关;BCAA虽与总胆红素呈负相关,但与白、球蛋白失去相关关系。     

肝硬化时蛋白质与氨基酸代谢的改变及其临床意义

肝硬化时,机体多处于分解代谢状态,蛋白质合成虽有增加,但仍相对不足。肝硬化患者多有较好的节氮效应。肝硬化时血浆芳香族氨基酸谱(AAA)上升,支链氨基酸(BCAA)和BCAA/AAA 比值减低。肝硬化时可能有BCAA 转运系统的调节异常及分布异常。AAA 水平取决于肝脏损害的程度。AAA 水平高常伴有负氮平衡,BCAA/AAA 比值是判断肝脏损害程度的一个敏感指标。血浆氨基酸谱改变与肝性脑病的程度不相关。     

肝病患者氨基酸代谢紊乱的意义及其治疗

许多临床观察和动物实验提示,肝性脑病和多种肝病时氨基酸代谢有明显改变,主要表现为血液中芳香族氨基酸(AAA)如苯丙氨酸和酪氨酸的增多以及支链氨基酸(BCAA)如缬氨酸、亮氨酸和异亮氨酸的减少。BCAA 减少及/或 AAA 增多导致 BCAA/AAA 克分子比值降低。与此同时,蛋氨酸和半胱氨酸等     

肝硬化时血浆支链氨基酸水平降低的机制

肝硬化时血浆氨基酸改变的特点是芳香族氨基酸(AAA)升高,支链氨基酸(BCAA)降低;这种改变的重要性在于它和肝性脑病有密切的关系.用富含BCAA的氨基酸液治疗肝性脑病的效益已为许多作者证实.因此,阐明血浆BCAA降低的机制和设计更合理的治疗有重要的意义.芳香族氨基酸主要在肝脏内代谢.肝硬化时血浆AAA水平的升高是由于肝清除能力减低之故.但支链氨基酸主要在外周组织内代谢,其降低与肝脏的代谢无关,而由下列多种因素引起.营养不良和饥饿肝病患者常因食欲不振、饮食习惯不良或有其它合并疾病而经常处于"饥饿"状态.长期饥饿使BCAA氧化供能增加,血浆BCAA降     

肝移植后血浆氨基酸变化与临床结果的关系

严重肝病时常表现为高氨基酸血症,芳香族氨基酸(AAA)(主要为苯丙氨酸,酪氨酸)升高;支链氨基酸(BCAA)(主要为亮氨酸、异亮氨酸和缬氨酸)略降低.BCAA/AAA的正常比值为3.0～3.5,肝衰时这一比值可降至2.0以下.作者观察9例原位肝移植患者移植前后的血浆氨基酸变化,研究其与移植肝功能状况及患者临床过程的关系.所有接受肝移植者均为晚期肝病患者.9例中3例因移植失败而再次作肝移植,其中1例存活.总计移植12次,共4例存活.术前测定血浆氨基酸浓度、胆红     

中国成人代谢综合征患者血清氨基酸水平改变的初步分析

目的分析中国成人MS患者血清氨基酸(AAs)水平变化,探讨AAs与MS的关系。方法选取2018年3月至2019年3月于北京医院体检人群616名,根据MS诊断标准分为MS组(MS,n=321)及无MS组(Con,n=295)。应用同位素稀释液相色谱串联质谱法检测MS患者血清支链氨基酸(BCAA)、芳香族氨基酸(AAA)、谷氨酸(Glu)、谷氨酰胺(Gln)、甘氨酸(Gly)和丙氨酸(Ala)水平,分析血清AAs水平变化。结果与Con组比较,MS组血清BCAA、AAA、Ala升高[62.15(55.01,69.83)vs 71.81(66.09,78.68)、39.56(36.44,43.86)vs 43.74(40.26,48.28)、40.33(34.98,46.09)vs 48.64(42.83,53.41),P<0.01],Gln/Glu、Gly降低[4.00(3.28,4.86)vs 3.11(2.36,3.99),23.85(20.68,27.84)vs 22.69(20.16,26.24),P<0.01]。Logistic回归分析显示,BCAA、Ala及Gln/Glu是MS的影响因素。结论中国成人MS患者血清BCAA、Ala升高,Gln/Glu降低。BCAA、Ala和Gln/Glu是MS的影响因素。     

丹参等对实验性肝纤维化鼠血浆氨基酸和白蛋白代谢的作用探讨

应用人血浆白蛋白(HSA)制备大鼠免疫性肝纤维化模型,并观察丹参注射液和重组白细胞介素2(IL-2)对血浆氨基酸、前白蛋白和白蛋白代谢的作用。结果显示丹参治疗组酪氨酸、苯丙氨酸减少,BCAA/AAA比值和前白蛋白、白蛋白高于肝纤维化对照动物和秋水仙硷治疗对照组。提示丹参注射液可促进免疫性肝纤维化大鼠前白蛋白和白蛋白的合成,并纠正其氨基酸代谢紊乱,改善肝功能。     

乙型肝炎血清氨基酸谱变化与肝功能相关性研究

肝脏受损伤时,普遍存在着氨基酸代谢的紊乱.肝脏受损的程度不同,血清氨基酸谱发生的改变也不相同,其特征性的改变表现为芳香族氨基酸(AAA,包括苯丙氨酸、酪氨酸)升高,支链氨基酸(BCAA,包括亮氨酸、异亮氨酸、缬氨酸)降低,BCAA/AA比值降低[1].     

Role of meal carbohydrate content for the imbalance of plasma amino acids in patients with liver cirrhosis

BACKGROUND AND AIM: Imbalance of circulating branched chain amino acids (BCAA) versus aromatic amino acids (AAA) and hyperinsulinemia are common metabolic alterations in patients with liver cirrhosis. The aim of this study was to characterize the effect of the carbohydrate component of a protein-rich mixed meal on postprandial plasma concentrations of 21 amino acids, insulin and C-peptide in patients with compensated liver cirrhosis. Furthermore, the effect of a dietary intervention on the metabolic alterations in cirrhotic patients was examined. METHODS: Eighteen patients with cirrhosis and 12 healthy volunteers received a protein-rich meal (pork filet 200 g) with or without carbohydrates (bread 50 g, glucose 20 g). A subgroup of four cirrhotic patients received an isoenergetic (117 kJ/kg bw) carbohydrate-enriched (60%) and -restricted (20%) diet for 7 days each. RESULTS: In the cirrhotic patients, basal plasma insulin and C-peptide concentrations were significantly elevated. The ingestion of a protein-rich meal without additional carbohydrates led to a significantly greater increase of insulin and C-peptide in the cirrhotic patients compared to controls. Postprandial increases of leucine and isoleucine were reduced, whereas those of phenylalanine were higher in cirrhotic patients. The addition of carbohydrates led to higher insulin and C-peptide plasma concentrations in cirrhotic patients. Postprandial BCAA increases were more impaired in the cirrhotic group after additional carbohydrate ingestion (46%vs 82%). After the carbohydrate-restricted diet for 7 days BCAA plasma levels increased but the BCAA/AAA ratio remained unaltered. CONCLUSIONS: The carbohydrate content of a meal enhances reduction of BCAA plasma concentrations in clinically stable cirrhotic patients. An imbalanced BCAA/AAA ratio cannot be avoided by a carbohydrate-reduced diet alone, supporting mandatory BCAA supplementation.     

Protein tolerance to standard and high protein meals in patients with liver cirrhosis

AIM To investigate the plasma amino acid response and tolerance to normal or high protein meals in patients with cirrhosis.METHODS The plasma amino acid response to a 20 g mixed protein meal was compared in 8 biopsy-proven compensated cirrhotic patients and 6 healthy subjects.In addition the response to a high protein meal(1 g/kg body weight) was studied in 6 decompensated biopsy-proven cirrhotics in order to evaluate their protein tolerance and the likelihood of developing hepatic encephalopathy(HE) following a porto-caval shunt procedure.To test for covert HE,the "number connection test"(NCT) was done on all patients,and an electroencephalogram was recorded in patients considered to be at Child-Pugh C stage.RESULTS The changes in plasma amino acids after a 20 g protein meal were similar in healthy subjects and in cirrhotics except for a significantly greater increase(P 0.05) in isoleucine,leucine and tyrosine concentrations in the cirrhotics.The baseline branched chain amino acids/aromatic amino acids(BCAA/AAA) ratio was higher in the healthy persons and remained stable-but it decreased significantly after the meal in the cirrhotic group.After the high protein meal there was a marked increase in the levels of most amino acids,but only small changes occurred in the levels of taurine,citrulline,cysteine andhistidine.The BCAA/AAA ratio was significantly higher 180 and 240 min after the meal.Slightly elevated basal plasma ammonia levels showed no particular pattern.Overt HE was not observed in any patients.CONCLUSION Patients with stable liver disease tolerate natural mixed meals with a standard protein content.The response to a high protein meal in decompensated cirrhotics suggests accumulation of some amino acids but it did not precipitate HE.These results support current nutritional guidelines that recommend a protein intake of 1.2-1.5 g/kg body weight/day for patients with cirrhosis.     

Characteristic pattern of free amino acids in plasma and skeletal muscle in stable hepatic cirrhosis

Free amino acid (AA) concentrations in plasma and quadriceps femoris muscle were determined in 19 healthy volunteers and in 16 patients with hepatic cirrhosis and portal hypertension. Nutritional state was impaired as judged by overt muscle wasting (9/16), triceps skinfold thickness less than 70% of normal in 8/14 (57%), and creatinine-height index below 70% in 5/12 (42%). In the plasma of patients the typical amino acid pattern of cirrhosis was to be observed: Elevation of tyrosine and methionine (p less than 0.01), uniform reduction of branched chain amino acids (p less than 0.001) resulting in a decreased molar ratio of BCAA/AAA from 2.85 +/- 0.05 in normal individuals to 1.35 +/- 0.12 in cirrhotics (p less than 0.001). Levels of the gluconeogenic AA glutamine, glutamate, aspartate, alanine, glycine, threonine, serine and lysine were lowered (p less than 0.05). In muscle of cirrhotics, intracellular AA concentrations exhibited a similar pattern with two major exceptions: Tyrosine and phenylalanine were augmented (p less than 0.001). Surprisingly, BCAA levels were altered heterogeneously; those of gluconeogenic BCAA decreased: Valine from 0.34 +/- 0.03 to 0.20 +/- 0.03 mmol/l (p less than 0.001), isoleucine 0.09 +/- 0.01 to 0.05 +/- 0.02 mmol/l. However, the concentration of ketogenic leucine remained unaltered in muscle. Nevertheless, the molar ratio of BCAA/AAA was considerably reduced from 3.70 +/- 0.04 to 0.81 +/- 0.08 (p less than 0.001). Most of the gluconeogenic AA exhibited reduced intramuscular concentrations, but glutamine levels were normal. The pattern of plasma and muscle free AA in hepatic cirrhosis is thus characterized by accumulation of aromatic AA and by depletion of gluconeogenic AA, especially BCAA.(ABSTRACT TRUNCATED AT 250 WORDS)     

粉防己碱对肝纤维化大鼠氨基酸代谢的影响

目的 观察粉防己碱对肝纤维化大鼠氨基酸代谢的影响。方法 应用四氯化碳制备大鼠肝纤维化模型。24只雄性SD大鼠随机分为正常对照组、病理对照组和粉防己碱治疗组,每组各8只,实验结束时心脏穿刺取血进行血浆氨基酸分析。结果 粉防己碱治疗组的支╱芳比值明显高于病理对照组。结论 粉防己碱具有改善肝纤维化大鼠氨基酸代谢的作用     

类风湿性关节炎患者血清游离氨基酸变化及其临床意义

目的了解类风湿性关节炎（ＲＡ）患者血清游离氨基酸的变化及其临床意义。方法应用高效液相色谱分析法分析了２５例ＲＡ患者血清中２７种游离氨基酸的变化,并与正常人血清游离氨基酸做比较。结果（１）ＲＡ患者血清中存在着多种氨基酸代谢紊乱,包括支链氨基酸与芳香族氨基酸比值（ＢＣＡＡ／ＡＡＡ）的降低（Ｐ＜００１）和必需氨基酸与非必需氨基酸（ＥＡＡ／ＮＥＡＡ）比值的降低（Ｐ＜００５）;（２）单剂量氨甲喋呤（７５ｍｇ）静脉注射后血清中谷氨酸、天冬氨酸、苏氨酸、酪氨酸升高,ＢＣＡＡ／ＡＡＡ比值进一步降低（Ｐ＜００５）。结论（１）ＲＡ患者在氨甲喋呤治疗前已有肝功能的异常,治疗后此种异常加重;（２）对长期应用氨甲喋呤治疗的ＲＡ患者进行选择性补充氨基酸治疗可能对保护肝功能及缓解病情有利。     

Measurement of serum branched-chain amino acids to tyrosine ratio level is useful in a prediction of a change of serum albumin level in chronic liver disease.

Aim: In patients with hepatitis C virus (HCV)-associated chronic liver diseases, especially in those with liver cirrhosis, accurate evaluation of their protein nutrition status is very important to improve their quality of life. Whereas the serum albumin level is commonly used to evaluate patients' protein nutrition status, in the present study, the serum amino acid levels were measured, as they also provide valuable information. Methods: Serum albumin levels and branched-chain amino acids (BCAA) to tyrosine ratio (BTR) were determined in 447 patients with HCV-associated chronic liver diseases (313 with chronic hepatitis and 134 with liver cirrhosis). Results: Chronic hepatitis progressed to liver cirrhosis, serum albumin and serum BTR levels decreased significantlyas chronic hepatitis progressed to liver cirrhosis. Hypoalbuminemia was significantly more common in patients with liver cirrhosis than in those with chronic hepatitis; however, the incidence of an amino acid imbalance was significantly higher than that of hypoalbuminemia in patients with liver cirrhosis. The presence of an amino acid imbalance was associated with a reduction in the serum albumin level 1 year later. Conclusions: It is important to evaluate serum albumin levels and the BTR in patients with HCV-associated chronic liver diseases.     

Effects of late evening snack including branched‐chain amino acid on the function of hepatic parenchymal cells in patients with liver cirrhosis

Aim: A late evening snack (LES) improves protein‐energy malnutrition due to overnight starvation and the catabolic state in patients with liver cirrhosis. Our aim was to examine whether LES including a branched‐chain amino acid (BCAA) could maintain hepatic reserve and the function of hepatic parenchymal cells in patients with liver cirrhosis, including those in the early stage of disease. Methods: Seventeen patients with liver cirrhosis received LES with a BCAA‐enriched nutrient mixture. During the study period, each patient was instructed on energy and protein intake. Indicators of liver function measured at 6 months included maximum asialoscintigraphic removal (Rmax: indicator of total liver receptors), asialoscintigraphic imaging grade, serum albumin, ammonia, tyrosine and BTR (molar ratio of branched‐chain amino acids to tyrosine). Results: Serum albumin levels, BTR and tyrosine levels of the 17 patients were significantly improved after nutrient treatment. In patients with Rmax of 0.2 or higher, serum albumin level and tyrosine level were significantly improved. Conclusion: LES with BCAA‐enriched nutrient therapy can improve protein malnutrition in patients with liver cirrhosis, and is more useful in the early stages of liver cirrhosis in improving hepatic parenchymal cell mass.     

Branched-chain amino acid metabolism in isolated perfused liver of cirrhotic rats.

We examined the possible contribution of the liver to the alterations in branched-chain amino acid (BCAA) metabolism in cirrhosis. The livers of male Sprague-Dawley rats with CCl4-induced cirrhosis were removed and placed in a recirculating perfusion system. Net amino acid uptake and release were determined over 55 min. Results were compared with those obtained with control animals, which were either pair-fed or fed ad libitum. Intrahepatic amino acid concentrations were determined at the end of the perfusion. The release of isoleucine and leucine was significantly lower in the cirrhotic livers than in the controls fed ad libitum. There was no difference between the cirrhotic and pair-fed groups with regard to the fluxes of the three BCAA. Intrahepatic concentrations of BCAA were reduced only in pair-fed controls. These results suggest that both cirrhosis and a low protein/calorie diet alter hepatic BCAA flux, but via different mechanisms. In cirrhosis, alterations could be due both to low food intake and to BCAA metabolism in non-parenchymal cells.     

Preservation of portal pressure improves growth and metabolic profile in the male portacaval-shunted rat

The portacaval anastomosis (PCA) rat model and human cirrhosis have many metabolic and nutritional abnormalities in common, such as growth retardation, hepatic and gonadal atrophy, and hyperammonemia. The severity of these abnormalities is variable and may be related to a number of factors, including portal pressure, portosystemic shunting, dietary intake, and how efficiently food is used. Therefore, this rat model was used to study these variables with the intent of gaining insights for improving the management of portal hypertension and malnutrition in human cirrhosis. A nonsuture end-to-side PCA (N = 100) or sham surgery (N = 71) was performed in 100 male rats. Four weeks after surgery, body and organ weights, food intake, serum ammonia, and serum amino acids were measured at death. In a subgroup of rats, (sham 7; PCA 34) portal venous pressure, degree of portosystemic shunting, and organ and body weights were obtained at death. Growth, liver weight, and testes weight were decreased, ammonia levels were higher, and the ratios of branched chain to aromatic amino acid (BCAA/AAA) were lower in the PCA group compared to the sham animals (P < 0.05). Since spleen weights correlated with portal pressure (P = 0.01), the PCA animals were then divided into those with preserved and those with low portal pressures based on spleen weight. The PCA group with preserved portal pressure had better growth, larger livers and testes, lower serum ammonia, and higher BCAA/AAA levels than the PCA group with low portal pressure; improvements associated with normal amounts of food intake and better food efficiency than the low pressure animals (P < 0.05 or better). Sham animals had no portosystemic shunting, while 100% shunting occurred in both PCA groups regardless of the portal pressure. In conclusion, preservation of portal pressure after portacaval anastomosis provides metabolic and nutritional benefits, which are independent of portosystemic shunting and associated with normal dietary intake and better preserved food efficiency.