支链氨基酸输液的临床应用

1976年Fischer 根据重症肝病时存在氨基酸失调和支链氨基酸代谢特点和生理功能,首先设计了含支链氨基酸较高的输液FO—80治疗肝昏迷获得显著效果。目前,我国也相继研制成功多种支链氨基酸输液用于临床,均取得与文献报道类似的效果,现将有关支链氨基酸输液的临床应用介绍如下:     

支链氨基酸代谢在糖肽类和环脂肽类抗生素产量提高与组分优化中的应用

摘要：糖肽类和环脂肽类抗生素具有很好的抗菌活性,临床上广泛用于治疗多重耐药菌导致的严重感染。大部分糖肽类和 环脂肽类抗生素均含有带支链结构的脂肪酸侧链,侧链结构差异是导致这两类抗生素发酵组分多样性的主要原因。支链脂肪酸 侧链的合成起始于支链氨基酸分解代谢,调控支链氨基酸代谢对于定向合成含有特定脂肪酸侧链的糖肽类和环脂肽类抗生素具 有重要作用。本文从糖肽类和环脂肽类抗生素中脂肪酸侧链的生源途径、外源添加支链氨基酸对糖肽类和环脂肽类抗生素产量 和组分的影响,内部改造支链氨基酸代谢途径对糖肽类和环脂肪肽类抗生素产量和组分的影响3方面进行了综述。     

支链氨基酸对动物实验性肝损伤作用的研究

目的:研究支链氨基酸(Branched Chain Amino Acid,BCAA)对动物实验性肝损伤的保护作用.方法:采用化学毒物D-氨基半乳糖胺盐酸盐(D-Galn)急性肝损伤模型,四氯化碳(CCl4)急性肝损伤模型,观察支链氨基酸对肝损伤动物生化指标和病理组织学改变的影响.结果:1.支链氨基酸高、低剂量组均对小鼠D-Galn肝损伤ALT及AST增高有明显的降低作用(P<0.01、P<0.05),支链氨基酸+乙肝宁联合用药组比单纯用乙肝宁组降酶作用更强(P<0.01).病理组织学检查结果:支链氨基酸对D-Galn引起的肝细胞变性、坏死等病变有明显改善作用,与模型组相比,高剂量组改善56.4%,低剂量组改善52%,乙肝宁+氨基酸混合用药组改善更明显为71.6%.2.支链氨基酸高剂量组对大鼠CCl4肝损伤ALT、AST活性增加及胆红素含量增高有明显的降低作用(P<0.01).病理组织学检查结果:支链氨基酸对CCl4肝损伤引起的肝细胞变性、坏死等病变有明显改善作用,与模型组相比,高剂量组改善27%,乙肝宁+氨基酸混合用药组改善28.2%.结论:支链氨基酸对小鼠D-Galn肝损伤及大鼠CCl4肝损伤具有保护作用.     

支链氨基酸对动物实验性肝损伤作用的研究

目的 :研究支链氨基酸 (BranchedChainAminoAcid ,BCAA)对动物实验性肝损伤的保护作用。方法 :采用化学毒物D 氨基半乳糖胺盐酸盐 (D Galn)急性肝损伤模型 ,四氯化碳 (CCl4 )急性肝损伤模型 ,观察支链氨基酸对肝损伤动物生化指标和病理组织学改变的影响。结果 :1 .支链氨基酸高、低剂量组均对小鼠D Galn肝损伤ALT及AST增高有明显的降低作用 (P <0 . 0 1、P <0 . 0 5) ,支链氨基酸 乙肝宁联合用药组比单纯用乙肝宁组降酶作用更强 (P <0 . 0 1 )。病理组织学检查结果 :支链氨基酸对D Galn引起的肝细胞变性、坏死等病变有明显改善作用 ,与模型组相比 ,高剂量组改善 56. 4 % ,低剂量组改善 52 % ,乙肝宁 氨基酸混合用药组改善更明显为 71 . 6%。 2 .支链氨基酸高剂量组对大鼠CCl4 肝损伤ALT、AST活性增加及胆红素含量增高有明显的降低作用 (P <0 . 0 1 )。病理组织学检查结果 :支链氨基酸对CCl4 肝损伤引起的肝细胞变性、坏死等病变有明显改善作用 ,与模型组相比 ,高剂量组改善 2 7% ,乙肝宁 氨基酸混合用药组改善 2 8. 2 %。结论 :支链氨基酸对小鼠D Galn肝损伤及大鼠CCl4 肝损伤具有保护作用。     

长期吃增肌蛋白粉,或不利于健康

<正>不少健身爱好者喜欢服用蛋白粉帮助增加肌肉量。澳大利亚悉尼大学一项小鼠实验显示,长期服用蛋白粉补剂可能不利于健康。增肌蛋白粉富含支链氨基酸。支链氨基酸是蛋白质中亮氨酸、缬氨酸和异亮氨酸这三种常见氨基酸的统称,有助增加肌肉量。研究人员给实     

治疗肝昏迷药14氨基酸注射液-800

肝昏迷是严重肝衰竭的主要表现,预后很差,病死率极高,其发病机制十分复杂。随着对肝昏迷起因的深入研究:1971年Fischer提出“假性神经传递介质学说”,认为肝昏迷的发生可能是由于血液和大脑中氨基酸浓度的变化与平衡失调所致,其中尤其是支链氨基酸与芳香氨基酸的比例失调,从而引起中枢神经传递介质的代谢紊乱。如果采用输注普通的复方氨基酸输液,不仅不能纠正氨基酸谱的紊乱,相反会诱发和加重肝昏迷症状。为了探索含高支链氨基酸输液对肝性脑症治疗效果和临床反应,上海医药工业研究院、上海长征制药厂与上海第二医学     

支链氨基酸对动物实验性肝损伤作用的研究

目的：研究支链氨基酸（Ｂｒａｎｃｈｅｄ Ｃｈａｉｎ Ａｍｉｎｏ Ａｃｉｄ,ＢＣＢＡＡ）对动物实验性肝损伤的保护作用。方法：采用化学毒物Ｄ－氨基半乳糖胺盐酸盐（Ｄ－Ｇａｌｎ）急性肝损伤模型,四氯化碳（ＣＣｌ４）急性肝损伤模型,观察支链氨基酸对肝损伤动物生化指标和病理组织学改变的影响。结果：１．支链氨基酸高、低剂量组均对小鼠Ｄ－Ｇａｌｎ肝损伤ＡＬＴ及ＡＳＴ增高有明显的降低作用（Ｐ〈０．０１,Ｐ〈０．０５）,支链氨基酸＋乙肝宁联合用药组比单纯用乙肝宁组降酶作用更强（Ｐ〈０．０１）。病理组织学检查结果：支链氨基酸对Ｄ－Ｇａｌｎ引起的肝细胞变性、坏死等病变有明显改善作用,与组相比,高剂量组改善５６．４％,低剂量组改善５２％,乙肝宁＋氨基酸混合用药组改善更明显的降低作用（Ｐ〈０．０１）。病理组织学检查结果：支链氨基酸对ＣＣ     

支链氨基酸在外科危重患者中的应用

<正>在手术、创伤、感染等应激状态下,危重患者主要表现为蛋白质代谢亢进,分解代谢增强而出现负氮平衡。支链氨基酸(BCAA)具有促进蛋白质的合成和抑制蛋白质分解的作用,它的应用有助于纠正危重患者的负氮平衡。本文研究富含BCAA的肠外营养液对外科危重患者在营养状况和临床转归方面的影响。     

支链氨基酸制剂治疗重症肝炎的得失

一般认为,重症肝炎给予支链氨基酸制剂可有助于供给能量、节约蛋白及对维持和改善肝脏氨基酸清除率有意义。但在与其它疗法合并使用时,需要避免水分过剩、高氨血症以及高渗透压等医原性因素。本文作者对重症肝炎患者使用支链氨基酸的得失进行了研究。研究对象是16例给予支链氨基酸制剂的重症肝炎患者(其中急性型11例,亚急性型5例),作者调查了给予该制剂前后患者的血糖、血中氨、Fischer比值、中心静脉压、尿素氮等变化以及脑水肿、肺瘀血和肾功能不全等合并症,并研究了该制剂的给予量与给予时     

支链氨基酸静脉滴注速度过快致DIC 2例报告

支链氨基酸是治疗肝病尤其是严重肝病伴有肝性脑病的常用药,临床正确使用效果显著且安全。笔者治疗2例因静脉滴注支链氨基酸速度过快,引起过敏反应且导致DIC的病例,报告如下:     

New therapeutic strategy for amino acid medicine: notable functions of branched chain amino acids as biological regulators

The branched chain amino acids (BCAAs) leucine, isoleucine, and valine are the most abundant of the essential amino acids. BCAAs have recently been recognized as having functions other than simple nutrition. The importance of BCAAs as nutrient regulators in protein synthesis was recognized over 20 years ago. Leucine is the most potent of the BCAAs in stimulating muscle protein synthesis, while isoleucine and valine are much less effective. The signaling action of leucine in protein synthesis has been well studied, and the mechanisms are currently under investigation. However, the pharmacological effects of isoleucine and valine have not been clarified. It has recently been reported that, among the BCAAs, leucine and isoleucine act as signals in glucose metabolism. We revealed that isoleucine stimulates both glucose uptake in the muscle and whole body glucose oxidation, in addition to depressing gluconeogenesis in the liver, thereby leading to a hypoglycemic effect in rats. Based on these results, we speculate that isoleucine signaling accelerates catabolism of incorporated glucose for energy production and consumption.     

The relationship between the contents of 13 amino acids in brain tissues and the progression of NAFLD via C57BL/6 model mice

Non-alcoholic fatty liver disease (NAFLD) is the steatosis of liver parenchyma unrelated to alcoholism, autoimmunity, and viral infection. It is also a metabolism-related syndrome, which has an unseparated relationship with adipose tissue dysfunction and obesity. Hepatic encephalopathy (HE) is one of the severe complications of chronic liver disease and one of the end-stage syndromes of liver disease. Some researchers have suggested that NAFLD, like other forms of liver injury, may be related to the metabolic disorder of branched-chain amino acids (BCAAs), which have been approved to be associated with HE influencing ammonia and energy metabolism. However, several studies have revealed the relationship among amino acids in serum, HE, and chronic liver disease; there are few studies on the contents of amino acids in brain tissues of an animal model with NAFLD. In the present research, we established a NAFLD mouse model with C57BL/6 mice and determined the contents of 13 amino acids in brain tissues of model mice by HPLC-FLD derivatization method using ortho-phthalaldehyde (OPA) to explore the relationship between the contents of amino acids in brain tissues and the progression of NAFLD. Moreover, the study showed that the changes of amino acid contents in the brain of the C57BL/6 mice were associated with the advancement of NAFLD, and this change might be related to the mechanism of HE.     

Branched-chain amino acids increase the seizure threshold to picrotoxin in rats.

During infusion of branched-chain amino acids (BCAAs) in humans, changes in ventilatory drive, appetite, and sleep have been reported. The mechanism by which BCAAs exert their effects on CNS remains unclear. Picrotoxin is a proconvulsant drug, acting as an antagonist on the GABA-benzodiazepine receptor complex. Twenty rats were randomized to receive either an IP injection with 4% BCAAs (300 mg/kg; 8 ml/kg) (n = 10) or placebo (saline 8 ml/kg) (n = 10). The mean latency time from injection to onset of seizures was recorded as an indication of the seizure threshold. Latency time was significantly longer for BCAAs than for placebo, 11.2 (+/- 1.9) vs. 8.3 (+/- 1.8) min. Thus, a BCAA injection increased the seizure threshold to picrotoxin (p < 0.03). This suggests that BCAA infusion may exert effects on the GABA-benzodiazepine receptor complex.     

Functional microbiomics reveals branched-chain amino acids depletion for alleviation of insulin resistance by berberine

Increased circulating branched-chain amino acids(BCAAs) have been involved in the pathogenesis of obesity and insulin resistance. However, evidence relating berberine(BBR), gut microbiota, BCAAs, and insulin resistance is limited. Here, we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet(HFD)-fed mice. BBR reorganized gut microbiota populations under both the normal chow diet(NCD) and HFD. Particularly, BBR noticeably decreased the relative abundance of BCAA-producing bacteria, including order Clostridiales; families Streptococcaceae, Clostridiaceae, and Prevotellaceae; and genera Streptococcus and Prevotella. Compared with the HFD group, predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment. Accordingly, the elevated serum BCAAs of HFD group were significantly decreased by BBR. Furthermore, the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by activation of the multienzyme branched-chain α-ketoacid dehydrogenase complex, whereas by inhibition of the phosphorylation state of BCKDHA(E1α subunit) and branched-chain α-ketoacid dehydrogenase kinase. The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3 T3-L1 adipocytes. Finally, data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs. Besides, functional microbiomics integrated high-throughput microbial genomics, metabolomics and molecular biotechnology has also been successfully applied to reveal the anti-obesity mechanism of hydroxysafflor yellow A.     

Effect of decreased BCAA synthesis through disruption of <Emphasis Type="Italic">ilvC</Emphasis> gene on the virulence of <Emphasis Type="Italic">Streptococcus pneumoniae</Emphasis>

Streptococcus pneumoniae (pneumococcus) is responsible for significant morbidity and mortality worldwide. It causes a variety of life-threatening infections such as pneumonia, bacteremia, and meningitis. In bacterial physiology, the metabolic pathway of branched-chain amino acids (BCAAs) plays an important role in virulence. Nonetheless, the function of IlvC, one of the enzymes involved in the biosynthesis of BCAAs, in S. pneumoniae remains unclear. Here, we demonstrated that downregulation of BCAA biosynthesis by ilvC ablation can diminish BCAA concentration and expression of pneumolysin (Ply) and LytA, and subsequently attenuate virulence. Infection with an ilvC mutant showed significantly reduced mortality and colonization in comparison with strain D39 (serotype 2, wild type), suggesting that ilvC can potentiate S. pneumoniae virulence due to adequate BCAA synthesis. Taken together, these results suggest that the function of ilvC in BCAA synthesis is essential for virulence factor and could play an important role in the pathogenesis of respiratory infections.     

Clinical significance and potential role of trimethylamine N-oxide in neurological and neuropsychiatric disorders

In the past three decades, research on the gut microbiome and its metabolites, such as trimethylamines (TMA), trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), branched-chain amino acids (BCAAs), bile acids, tryptophan and indole derivatives, has attracted the attention of many scientists and industrialists. Among these metabolites, TMAO is produced from dietary choline, phosphatidylcholine, carnitine, and betaine. TMAO and other gut metabolites, such as TMA and SCFAs, reach the brain by crossing the blood–brain barrier (BBB) and are involved in brain development, neurogenesis, and behavior. Gut-microbiota composition is influenced by diet, lifestyle, antibiotics, and age. Several studies have confirmed that altered TMAO levels contribute to metabolic, vascular, psychiatric, and neurodegenerative disorders. This review focuses on how altered TMAO levels impact oxidative stress, microglial activation, and the apoptosis of neurons, and may lead to neuroinflammation, which can subsequently result in the development of psychiatric, cognitive, and behavioral disorders.     

Reabsorption of neutral amino acids mediated by amino acid transporter LAT2 and TAT1 in the basolateral membrane of proximal tubule

In order to understand the renal reabsorption mechanism of neutral amino acids via amino acid transporters, we have isolated human L-type amino acid transporter 2 (hLAT2) and human T-type amino acid transporter 1 (hTAT1) in human, then, we have examined and compared the gene structures, the functional characterizations and the localization in human kidney. Northern blot analysis showed that hLAT2 mRNA was expressed at high levels in the heart, brain, placenta, kidney, spleen, prostate, testis, ovary, lymph node and the fetal liver. The hTAT1 mRNA was detected at high levels in the heart, placenta, liver, skeletal muscle, kidney, pancreas, spleen, thymus and prostate. Immunohistochemical analysis on the human kidney revealed that the hLAT2 and hTAT1 proteins coexist in the basolateral membrane of the renal proximal tubules. The hLAT2 transports all neutral amino acids and hTAT1 transports aromatic amino acids. The basolateral location of the hLAT2 and hTAT1 proteins in the renal proximal tubule as well as the amino acid transport activity of hLAT2 and hTAT1 suggests that these transporters contribute to the renal reabsorption of neutral and aromatic amino acids in the basolateral domain of epithelial proximal tubule cells, respectively. Therefore, LAT2 and TAT1 play essential roles in the reabsorption of neutral amino acids from the epithelial cells to the blood stream in the kidney. Because LAT2 and TAT1 are essential to the efficient absorption of neutral amino acids from the kidney, their defects might be involved in the pathogenesis of disorders caused by a disruption in amino acid absorption such as blue diaper syndrome.     

L-type Amino Acid Transporter 1 (SLC7A5)-Mediated Transport of Pregabalin at the Rat Blood-Spinal Cord Barrier and its Sensitivity to Plasma Branched-Chain Amino Acids

Pregabalin is an anti-neuropathic pain drug inhibiting the α2δ subunit of the voltage-dependent calcium channel in the spinal cord. The aim of this study is to characterize the transport mechanism of pregabalin at the blood-spinal cord barrier (BSCB) by means of in vivo experiments in rats and in vitro studies using primary-cultured rat spinal cord endothelial cells. We isolated endothelial cells by culturing rat spinal cord tissue in the presence of puromycin, and confirmed the expression of BSCB markers such as Cd31, Mdr1a, and Claudin-5. The uptake of pregabalin by primary-cultured rat spinal cord endothelial cells was sodium-independent and was significantly inhibited by L-leucine, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid, and JPH203. These results suggest the involvement of L-type amino acid transporter (LAT) 1. LAT1 mRNA and protein was expressed in primary-cultured rat spinal cord endothelial cells, which is consistent with LAT1 expression at the BSCB. In the in vivo study, the transfer of pregabalin to rat spinal cord and brain was significantly decreased by the pre-administration of branched chain amino acids (BCAAs), which are endogenous substrates of LAT1. Our results indicate that pregabalin transport across the BSCB is mediated at least in part by LAT1 and is inhibited by plasma BCAAs.     

肝癌术后患者的营养支持治疗方案探讨

目的探讨肝癌术后患者的营养支持治疗方案对术后机体营养和肝功能恢复的作用。方法通过对1例肝癌术后患者营养支持方案的分析,按其经口饮食恢复的情况将营养支持治疗分为禁食、低脂流质、低脂普食3个阶段,不同阶段根据具体的生理病理情况制定不同的肠外营养支持方案。临床药师参与整个过程,并推荐个体化的营养制剂,提供合理化的方案。结果对于肝癌术后患者,选择复方碳水化合物和脂肪乳剂组成的双能源提供热卡,以富含支链氨基酸的复方氨基酸制剂作为氮源,利于减轻肝脏负担,促进术后机体营养和肝功能的恢复。结论肝癌术后肝功能恢复期,制定良好的营养支持方案,临床药师参与选择适宜的营养药物制剂,能使支持治疗达到了较好的效果。