CN113797188A - 支链氨基酸在制备缓解术后胰岛素抵抗制剂中的应用 - Google Patents
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Abstract
本发明涉及支链氨基酸在制备缓解术后胰岛素抵抗制剂中的应用，所述支链氨基酸包括：亮氨酸、缬氨酸以及异亮氨酸。本发明的制剂能够有效缓解患者术后胰岛素抵抗，降低术后空腹高血糖，减少伤口感染和围手术期其他并发症，适用于外科手术患者的加速康复；本发明为术后胰岛素抵抗及术后高血糖的预防和治疗提供了新的方法和思路，对于寻求新的术前干预措施和积极有效的分子靶点，有较大的理论价值和现实意义。
Description
技术领域
本发明涉及外科临床营养技术领域，尤其涉及支链氨基酸在制备缓解术后胰岛素抵抗制剂中的应用。
背景技术
术后胰岛素抵抗指继发于手术后，胰岛素作用机体摄取葡萄糖能力降低或胰岛素对肝脏葡萄糖输出的抑制作用减弱导致术后空腹血糖应激性升高的现象。
手术创伤引起一系列的应激反应，对病人术后代谢、器官功能及康复进程都有影响，特别是术后的胰岛素抵抗引起的高血糖现象，是术后并发症及康复速度相关的重要因素。术后应激性高血糖，特别是血糖水平超过180mg/dL，与围手术期的不良临床结果(包括免疫功能受损、手术部位感染、伤口愈合延迟和住院时间延长)之间存在明确的关联。术前禁食禁饮、手术过程、术后疼痛和活动减少等都会引起机体术后胰岛素抵抗。
加速康复举措如微创技术、良好的止痛、术前口服碳水化合物都可以在一定程度上降低患者对手术的应激反应，减轻术后胰岛素抵抗引起的糖代谢异常，加速患者术后康复，但不能完全阻止术后应激性高血糖的发生。因此，继续探究并完善围术期加速康复干预措施，进一步降低术后应激性胰岛素抵抗，也是亟待解决的临床问题。
近年来，有关支链氨基酸与代谢性疾病的研究成为了热点。支链氨基酸是指α碳上含有分支侧链的氨基酸，包括亮氨酸、异亮氨酸和缬氨酸，它们都属于人体内不能合成而必须从外源摄入的氨基酸，是维持动物机体生长需要的营养物质，也是重要的营养代谢信号分子。最近几年临床研究发现支链氨基酸代谢紊乱与糖尿病的发生发展紧密相关，血清支链氨基酸水平甚至可以预测糖尿病的发生及治疗手段的预后。基础研究则报道了高支链氨基酸具有促进或抑制糖代谢的两种截然不同的效果，原因尚不清楚。
支链氨基酸与慢性胰岛素抵抗有关联，但支链氨基酸与术后胰岛素抵抗(急性胰岛素抵抗)的研究还罕有报道。目前尚无文献报道通过术前支链氨基酸摄入来干预术后胰岛素抵抗的措施。
发明内容
围手术期应激引起的术后胰岛素抵抗，主要表现为术后空腹血糖升高，是患者预后的独立危险因素，它可增加术后并发症的发生率和患者死亡率。本发明的目的是针对现有技术中的不足，提供支链氨基酸在制备缓解术后胰岛素抵抗制剂中的应用。
为实现上述目的，本发明采取的技术方案是：
提供支链氨基酸在制备缓解术后胰岛素抵抗制剂中的应用，所述支链氨基酸包括：亮氨酸、缬氨酸以及异亮氨酸。
优选地，所述支链氨基酸在所述制剂中的总浓度为20mg/mL～30mg/mL。
更优选地，所述支链氨基酸在所述制剂中的总浓度为25mg/mL。
优选地，三种所述支链氨基酸的质量比选自亮氨酸：缬氨酸：异亮氨酸＝1:1:1、亮氨酸：缬氨酸：异亮氨酸＝2:1:1或亮氨酸：缬氨酸：异亮氨酸＝4:1:1。
更优选地，三种所述支链氨基酸的质量比为亮氨酸：缬氨酸：异亮氨酸＝1:1:1。
更优选地，三种所述支链氨基酸在所述制剂中的浓度均为8mg/mL～9mg/mL。
优选地，术前服用所述制剂能够降低术后的肝脏糖异生水平，从而缓解术后胰岛素抵抗。
本发明采用以上技术方案，与现有技术相比，具有如下技术效果：
本发明的制剂能够有效缓解患者术后胰岛素抵抗，降低术后空腹高血糖，减少伤口感染和围手术期其他并发症，适用于外科手术患者的加速康复；本发明为术后胰岛素抵抗及术后高血糖的预防和治疗提供了新的方法和思路，对于寻求新的术前干预措施和积极有效的分子靶点，有较大的理论价值和现实意义。
附图说明
图1为大鼠手术前后的血糖水平结果图(处死大鼠的时间为小肠部分切除术开始后4h)；
图2为大鼠手术前后的胰岛素水平结果图(处死大鼠的时间为小肠部分切除术开始后4h)；
图3是大鼠手术后胰岛素信号通路(PI3K-AKT-mTOR-p70S6K)WB结果图，图(a)是肝脏组织WB结果，图(b)是肌肉组织WB结果；
图4为大鼠手术后相对mRNA表达水平结果图；
图5为大鼠手术前后的血糖水平结果图(处死大鼠的时间为小肠部分切除术开始后0.5h)；
图6为大鼠手术前后的胰岛素水平结果图(处死大鼠的时间为小肠部分切除术开始后0.5h)；
其中，DDH2O表示纯水；BCAA表示支链氨基酸；ns表示无显著性差异；*p<0.05；**p<0.01。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有作出创造性劳动的前提下所获得的所有其他实施例，都属于本发明保护的范围。
需要说明的是，在不冲突的情况下，本发明中的实施例及实施例中的特征可以相互组合。
下面结合附图和具体实施例对本发明作进一步说明，但不作为本发明的限定。
实施例1
本实施例提供一种用于缓解术后胰岛素抵抗的支链氨基酸制剂，制备方法包括：取亮氨酸、缬氨酸以及异亮氨酸三种支链氨基酸粉末各100mg，于12mL水中溶解，即得所述支链氨基酸制剂。
实施例2
1)大鼠小肠部分切除术后胰岛素抵抗模型的建立
参照瑞典卡罗林斯卡医学院STROMMER教授的方法：选取200g左右雄性SD大鼠，手术前禁食17小时，先用异氟烷气体诱导麻醉，再腹腔注射使用10％水合氯醛350μL/100g进行麻醉。麻醉后心脏采血300μL并测即刻血糖。大鼠右侧颈动脉置管(预留采血)，麻醉后将大鼠仰卧位固定，颈部去毛、消毒，自颈正中剪开皮肤，分离出右侧颈动脉，远心端结扎并用动脉夹夹住近心端，在动脉壁上剪一个小口，往近心端方向插入直径0.9mm硅胶管(管内预先注入25U/mL肝素生理盐水溶液抗凝)，结扎固定插管，松开动脉夹，然后封住插管出口防止血液流出。每次取血后都用含肝素生理盐水溶液抗凝，防止插管堵塞。在腹部中线切开5厘米，在距屈氏韧带5厘米处断开2-3条肠系膜血管，取出5厘米长的小肠。用6/0缝线进行小肠吻合，然后用4/0缝线缝合腹部。整个手术持续约40分钟左右。术后大鼠置于37℃保温毯上。在麻醉后手术前和手术后30、60、90和120分钟各采集血样300微升。血样在4℃以3000转/分的速度离心20分钟，收集血浆并储存在-80℃。手术开始后4h处死大鼠，提取骨骼肌、肝组织、脂肪组织于液氮中，并储存在-80℃下。
2)支链氨基酸灌胃干预对大鼠术后胰岛素抵抗的影响
取6周龄200g雄性SD大鼠20只，按照灌胃成分分为2组，每组10只(术前2小时灌胃3mL)。分为纯水灌胃组、支链氨基酸灌胃组(即实施例1所述制剂)，记录大鼠术前体重。实行大鼠小肠部分切除术。葡萄糖氧化酶法测量血糖值，ELISA法测量血浆胰岛素值。
3)实验结果
大鼠手术前后的血糖水平如图1所示，大鼠手术前后的胰岛素水平如图2所示；根据图3所示，纯水灌胃组与支链氨基酸灌胃组间术后肝组织和肌肉组织的胰岛素通路没有明显差异；根据图4所示，支链氨基酸灌胃组术后肝脏糖异生关键酶G6PC1的转录显著降低；
将处死大鼠的时间改为小肠部分切除术开始后0.5h，大鼠手术前后的血糖水平如图5所示，大鼠手术前后的胰岛素水平如图6所示；
上述结果表明：术前2小时对大鼠实行支链氨基酸灌胃，可以抑制肝脏糖异生，降低术后高血糖，从而缓解术后胰岛素抵抗。
综上所述，本发明通过对大鼠实施小肠部分切除术，建立了腹部中等程度创伤的急性胰岛素抵抗动物模型，通过灌胃增加支链氨基酸摄入，探索通过改变支链氨基酸摄入影响术后胰岛素抵抗的可行性以及建立支链氨基酸与术后胰岛素抵抗的确切关联，从而为减轻患者术后胰岛素抵抗开发新的营养素提供实验依据。
以上所述仅为本发明较佳的实施例，并非因此限制本发明的实施方式及保护范围，对于本领域技术人员而言，应当能够意识到凡运用本发明说明书及图示内容所作出的等同替换和显而易见的变化所得到的方案，均应当包含在本发明的保护范围内。
Claims (7)
1.支链氨基酸在制备缓解术后胰岛素抵抗制剂中的应用，其特征在于，所述支链氨基酸包括：亮氨酸、缬氨酸以及异亮氨酸。
2.根据权利要求1所述的应用，其特征在于，所述支链氨基酸在所述制剂中的总浓度为20mg/mL～30mg/mL。
3.根据权利要求2所述的应用，其特征在于，所述支链氨基酸在所述制剂中的总浓度为25mg/mL。
4.根据权利要求3所述的应用，其特征在于，三种所述支链氨基酸的质量比选自亮氨酸：缬氨酸：异亮氨酸＝1:1:1、亮氨酸：缬氨酸：异亮氨酸＝2:1:1或亮氨酸：缬氨酸：异亮氨酸＝4:1:1。
5.根据权利要求4所述的应用，其特征在于，三种所述支链氨基酸的质量比为亮氨酸：缬氨酸：异亮氨酸＝1:1:1。
6.根据权利要求5所述的应用，其特征在于，三种所述支链氨基酸在所述制剂中的浓度均为8mg/mL～9mg/mL。
7.根据权利要求1所述的应用，其特征在于，术前服用所述制剂能够降低术后的肝脏糖异生水平，从而缓解术后胰岛素抵抗。
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002507188A (ja) * | 1996-08-30 | 2002-03-05 | イーライ・リリー・アンド・カンパニー | グルカゴン様ペプチド―１（ｇｌｐ―１）またはその同族体における外科処置後の異化変調を防止するための使用 |
| JP2003171271A (ja) * | 2001-09-26 | 2003-06-17 | Ajinomoto Co Inc | 耐糖能異常用薬剤 |
| JP2006028194A (ja) * | 2001-09-26 | 2006-02-02 | Ajinomoto Co Inc | 耐糖能異常用医薬組成物及び飲食品 |
| WO2007069744A1 (ja) * | 2005-12-16 | 2007-06-21 | Ajinomoto Co., Inc. | メタボリックシンドローム予防・改善用組成物 |
| US20150238441A1 (en) * | 2012-10-05 | 2015-08-27 | University Of Rochester | Modulation of Branched Amino Acid Concentrations to Treat Metabolic Diseases |
| US20200155589A1 (en) * | 2018-06-15 | 2020-05-21 | Gerald Haase | Composition For Enchanced Recovery After Surgery (ERAS) |
-
2021
- 2021-08-31 CN CN202111017017.4A patent/CN113797188A/zh active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002507188A (ja) * | 1996-08-30 | 2002-03-05 | イーライ・リリー・アンド・カンパニー | グルカゴン様ペプチド―１（ｇｌｐ―１）またはその同族体における外科処置後の異化変調を防止するための使用 |
| JP2003171271A (ja) * | 2001-09-26 | 2003-06-17 | Ajinomoto Co Inc | 耐糖能異常用薬剤 |
| JP2006028194A (ja) * | 2001-09-26 | 2006-02-02 | Ajinomoto Co Inc | 耐糖能異常用医薬組成物及び飲食品 |
| WO2007069744A1 (ja) * | 2005-12-16 | 2007-06-21 | Ajinomoto Co., Inc. | メタボリックシンドローム予防・改善用組成物 |
| US20150238441A1 (en) * | 2012-10-05 | 2015-08-27 | University Of Rochester | Modulation of Branched Amino Acid Concentrations to Treat Metabolic Diseases |
| US20200155589A1 (en) * | 2018-06-15 | 2020-05-21 | Gerald Haase | Composition For Enchanced Recovery After Surgery (ERAS) |
Non-Patent Citations (6)
| Title |
|---|
| GOJDA, J, ·STRAKOVÁ, ET AL: "Increased Incretin But Not Insulin Response after Oral versus Intravenous Branched Chain Amino Acids", NN NUTR METAB, vol. 05, no. 16, pages 355 - 361 * |
| ZHANG J，ET AL: "Preoperative administration of branched-chain amino acids reduces postoperative insulin resistance in rats by reducing liver gluconeogenesis", NUTR METAB (LOND), vol. 19, no. 01, pages 1 - 15 * |
| 杨文慧，等: "支链氨基酸代谢与胰岛素抵抗及2型糖尿病研究进展", 中华老年心脑血管病杂志, vol. 21, no. 04, pages 1009 - 1012 * |
| 杨海清，等: "肝癌患者围术期胰岛素抵抗的研究及护理启示", 护理学报, vol. 22, no. 02, pages 23 * |
| 王晓晓，等: "驴乳抑制胰岛素抵抗形成与氨基酸代谢的相关性", 食品安全质量检测学报, vol. 11, no. 15, pages 8 - 15 * |
| 金秋，等: "膳食补充亮氨酸对高脂饲喂大鼠胰岛素抵抗及肝脏糖原合成的影响", 营养学报, vol. 06, no. 02, pages 17 - 23 * |
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