CN113866399A - 肝脏酮体在急性胰腺炎病情监测和治疗上的应用 - Google Patents
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Abstract
本发明涉及一种肝脏酮体β‑羟基丁酸代谢在急性胰腺炎病情监测和治疗方面的应用，属于生物医药技术领域。本发明提供了一种肝脏酮体β‑羟基丁酸在制备用于诊断急性胰腺炎的诊断试剂中的应用，在制备用于对急性胰腺炎患者的病情进行监测的诊断试剂中的应用，在制备用于治疗急性胰腺炎的药物中的应用，通过本发明可以快速的对急性胰腺炎的严重程度进行预判，方便用于病情监测。为急性胰腺炎的治疗及预防提供了新的靶点和新的路径。
Description
技术领域
本发明涉及一种肝脏酮体β-羟基丁酸代谢在急性胰腺炎病情监测和治疗方面的应用，属于生物医药技术领域。
背景技术
急性胰腺炎是由多种病因引起胰酶在胰腺内被异常激活后引起组织自身消化、水肿、甚至坏死的炎症反应，是最常见的消化系统和胰腺外分泌疾病之一，其全球发病率逐年上升。急性胰腺炎的危险和致病因素复杂，包括肥胖、糖尿病、胆结石、过量饮酒、吸烟、基因突变等。大量的研究显示，持续性器官功能衰竭、胰腺坏死、脓毒症等系统和局部并发症与急性胰腺炎的病情转归密切相关。因此，2012年修订版亚特兰大分类标准，将急性胰腺炎按其严重程度分为轻度(mild acute pancreatitis，MAP)、中度重症(moderately severeacute pancreatitis，MSAP)、重症(severe acute pancreatitis，SAP)三个等级。大多数轻度急性胰腺炎患者病程轻，病程呈自限性，无系统和局部并发症，可于对症治疗后一周左右康复，预后好；约25％病人发展为中度重症急性胰腺炎，不伴有持续性器官功能衰竭，但通常伴有如急性坏死性积聚和急性胰周液体积聚等，部分病人因有局部并发症有症状或需要手术治疗，住院时间延长，病死率较低；约5％-20％病人发展为重症急性胰腺炎，由持续性全身炎性反应综合征进展为持续性器官功能衰竭或多器官功能衰竭，往往伴有显著胰腺坏死，胰腺、肺和血液等感染，较多病人需要重症监护治疗和胰腺手术，病死率＞30％。
急性胰腺炎病情严重程度分型：
轻度：
1.无器官衰竭；
2.无局部或系统性的并发症；
中度重症：
1.器官衰竭在48小时内缓解(一过性的器官衰竭)；
2.无局部或系统性的并发症不伴有持续的器官衰竭。
重症：
1.持续性器官衰竭(>48小时)
单器官衰竭；
多器官衰竭；
急性胰腺炎的临床诊断主要通过典型的病史，血尿淀粉酶、血清脂肪酶和炎性指标检测，以及影像学检查等。早期判定急性胰腺炎的病情对综合救治重症急性胰腺炎和转诊病人有极为重要的作用，但现在常规的临床评分预测重症急性胰腺炎和病死率的准确率仅能达到0.75左右。因此，临床上需要更为准确、简易的指标预测病情，监测治疗反应。另一方面，临床急性胰腺炎的治疗方案以保守治疗为主，手术治疗为辅，保守治疗主要包括禁食、抑制消化液分泌、液体复苏和镇痛等。但因缺乏特效、靶向于影响急性胰腺炎病理生理的特异性治疗方法，重症急性胰腺炎的治疗一直是临床的痛点和难点。肝损伤在急性胰腺炎中经常容易被忽视，酮体β-羟基丁酸(β-hydroxybutyrate，βOHB)是肝脏中生成的重要代谢产物，酮体由β-羟基丁酸、乙酰乙酸和丙酮组成，其中β-羟基丁酸是酮体中含量最多的一种成分。在肝脏中脂肪酸通过β-氧化产生酮体，合成的酮体被运送出肝组织，进入血液循环，最终被运送至肝外组织作为大脑、心脏和骨骼肌等器官的替代能源。近些年的研究发现，酮体β-羟基丁酸还可作为信号传导介质在炎症和免疫反应等多种病理情况下起着关键作用。β-羟基丁酸可以通过影响免疫细胞包括巨噬细胞和T细胞的活化及功能影响炎症反应炎，进而影响炎性疾病。经本发明的前期研究发现，血清β-羟基丁酸在轻度急性胰腺炎/中度重症急性胰腺炎中有明显的升高，在重症急性胰腺炎中并没有发生明显的变化，且其水平与血清肌酸激酶(rs＝-0.411)、乳酸脱氢酶(rs＝-0.416)、C-反应蛋白(rs＝-0.286)、白细胞介素-6(rs＝-0.365)、降钙素原(rs＝-0.339)、全身炎症反应综合征评分(rs＝-0.264)、格拉斯哥评分(rs＝-0.350)、急性生理学和慢性健康评估评分(rs＝-0.345)、序贯器官衰竭估计(rs＝-0.257)、修订的马歇尔评分(rs＝-0.342)和血清Ca2+水平(rs＝0.464)显著相关(所有P≤0.001)。经本发明的前期研究发现给急性胰腺炎小鼠喂食生酮食物或腹腔注射β-羟基丁酸可以缓解急性胰腺炎，因此给予急性胰腺炎病人生酮食物或是通过肠营养的方式给予β-羟基丁酸可能成为一种治疗急性胰腺的方式。对于反复发作的急性胰腺炎病人也可以通过适量给予生酮食物预防急性胰腺炎。
发明内容
本发明的目的是为解决一种肝脏酮体β-羟基丁酸代谢在急性胰腺炎病情监测和治疗方面的应用的技术问题。
为达到解决上述问题的目的，本发明所采取的技术方案是提供一种肝脏酮体β-羟基丁酸在制备用于诊断急性胰腺炎的诊断试剂中的应用，所述应用在于检测待诊者β-羟基丁酸的血清浓度。
本发明提供一种肝脏酮体β-羟基丁酸在制备用于对急性胰腺炎患者的病情进行监测的诊断试剂中的应用，所述应用在于检测患者β-羟基丁酸的血清浓度。
本发明提供一种基于肝脏酮体β-羟基丁酸在制备用于治疗急性胰腺炎的药物中的应用。
优选地，所述应用包括生酮饮食。
优选地，所述应用包括肠内营养或/和液体复苏时给予β-羟基丁酸或其衍生物/类似物。
本发明提供一种基于肝脏酮体β-羟基丁酸在制备用于预防急性胰腺炎的药物中的应用。
相比现有技术，本发明具有如下有益效果：
血清β-羟基丁酸与急性胰腺炎的严重程度密切相关，将其作为急性胰腺炎的诊断和病情监测指标，可以在病人入院后，快速的对急性胰腺炎的严重程度有个预判，并且血清检测的方式较为方便和快速，方便用于病情监测。
将代谢物质β-羟基丁酸或其衍生物/类似物用于治疗急性胰腺炎，为急性胰腺炎的治疗及预防提供了新的靶点和新的路径。
附图说明
图1为轻度、中度重症和重症急性胰腺炎的病人血清β-羟基丁酸水平变化分析图。
其中A图为轻度、中度重症和重症急性胰腺炎的病人血清β-羟基丁酸水平变化图。
B图为轻度和重症急性胰腺炎的小鼠血清β-羟基丁酸水平变化图。
C图为已被诊断为轻中症(非重症)，重症急性胰腺炎的病人，在入院后的第一天、第三天和第七天检测血清β-羟基丁酸水平变化图。
图2为β-羟基丁酸用于急性胰腺炎的治疗效果图。
其中A图为给予生酮食物1,3丁二醇喂食一周后，轻症急性胰腺炎小鼠胰腺组织损伤结果图；
B图显示给予生酮食物后胰腺部位炎性巨噬细胞变化图；
C图显示给予生酮食物后重症急性胰腺炎胰腺组织损伤结果图；
D图显示给予生酮食物后重症急性胰腺炎肺组织损伤结果图；
E图显示给予生酮食物后重症急性胰腺炎胰腺部位炎性巨噬细胞变化图。
具体实施方式
为使本发明更明显易懂，兹以优选实施例，并配合附图作详细说明如下：
本发明提供了一种肝脏酮体β-羟基丁酸在制备用于诊断急性胰腺炎的诊断试剂中的应用，所述应用在于检测待诊者β-羟基丁酸的血清浓度。
本发明提供了一种肝脏酮体β-羟基丁酸在制备用于对急性胰腺炎患者的病情进行监测的诊断试剂中的应用，所述应用在于检测患者β-羟基丁酸的血清浓度。
本发明提供了一种肝脏酮体β-羟基丁酸在制备用于治疗急性胰腺炎的药物中的应用。所述应用包括生酮饮食；包括肠内营养时给予β-羟基丁酸。
本发明提供了一种肝脏酮体β-羟基丁酸在制备用于预防急性胰腺炎的药物中的应用。
实施例
血清β-羟基丁酸用于急性胰腺炎的诊断和病情监测：
1.腹痛病人入院时取病人血清，通过生化自动分析仪检测血清β-羟基丁酸浓度。
2.若血清β-羟基丁酸浓度高于正常值，可初步判断可能为轻中症急性胰腺炎。进一步结合胰腺CT(computed tomography，计算机断层扫描)或MRI(magnetic resonanceimaging，核磁共振成像)的结果，若影像学结果提示为急性胰腺炎，可判定其为轻中症急性胰腺炎。
3.若血清β-羟基丁酸浓度在正常值范围内，则结合血清ALT(alanineaminotransferase,丙氨酸转移酶)以及CT(computed tomography，计算机断层扫描)或MRImagnetic resonance imaging，核磁共振成像)的结果，若影像学结果提示为急性胰腺炎，可判定其为重症急性胰腺炎。
4.对于已判定为轻中症急性胰腺炎的病人，可每日检测血清β-羟基丁酸浓度，若浓度较之前升高则说明急性胰腺炎加重，若浓度不变或是降低，则结合血清ALT(alanineaminotransferase,丙氨酸转移酶)以及CT(computed tomography，计算机断层扫描)或MRI(magnetic resonance imaging，核磁共振成像)的结果，判定急性胰腺炎缓解或是向重症急性胰腺炎加重。
注：所有的急性胰腺炎病人诊断需要排除本身就患有糖尿病和肝脏疾病的病人。
β-羟基丁酸用于急性胰腺炎的治疗：
1.对于急性胰腺炎病人，可以在肠内营养治疗时加入β-羟基丁酸，用于治疗急性胰腺炎。
对于反复发作的急性胰腺炎病人，可以通过摄取生酮食物，预防急性胰腺炎的发生。
如图1所示：血清β-羟基丁酸用于急性胰腺炎的诊断和病情监测：
在图1的A图中，已经被诊断为轻度、中度重症和重症急性胰腺炎的病人，轻度和中度重症急性胰腺炎病人血清β-羟基丁酸水平都有明显的升高，而重症急性胰腺炎病人血清β-羟基丁酸并没有明显的变化；与之相似的，在图1的B图中小鼠的轻度急性胰腺炎和重症急性胰腺炎中血清β-羟基丁酸也出现了同样的趋势。说明血清β-羟基丁酸的水平确实是与急性胰腺炎的严重程度密切相关。
在图1的C图中，已被诊断为轻中症(非重症)急性胰腺炎的病人，在入院后的第一天、第三天和第七天检测血清β-羟基丁酸是呈先升高后降低的趋势，说明急性胰腺炎在加重之后有所缓解，并且其血清β-羟基丁酸水平相对高于重症急性胰腺炎病人。说明血清β-羟基丁酸水平可以监测急性胰腺炎的病情。
图1中图注：n:number病人数量；p：是指两样本间的统计学差异，p值越小说明两样本差异越明显。
如图2所示：β-羟基丁酸用于急性胰腺炎的治疗：
在图2的A图中，在给予生酮食物1,3丁二醇喂食一周后，轻症急性胰腺炎(雨蛙素*7)小鼠胰腺组织损伤有明显的缓解，并且图2的B图显示胰腺部位炎性巨噬细胞也明显减少。说明生酮饮食可以治疗轻症急性胰腺炎。
在图2的C、D和E图中，在给予生酮食物1,3丁二醇喂食一周后，重症急性胰腺炎(雨蛙素*12)小鼠胰腺和肺组织损伤有明显的缓解，并且胰腺部位炎性巨噬细胞也明显减少。说明生酮饮食可以治疗重症急性胰腺炎。
图2中的图注：p：是指两样本间的统计学差异，p值越小说明两样本差异越明显；TNF-α:tumor necrosis factor-α，肿瘤坏死因子α，表达于炎性巨噬细胞表面。
以上所述，仅为本发明的较佳实施例，并非对本发明任何形式上和实质上的限制，应当指出，对于本技术领域的普通技术人员，在不脱离本发明的前提下，还将可以做出若干改进和补充，这些改进和补充也应视为本发明的保护范围。凡熟悉本专业的技术人员，在不脱离本发明的精神和范围的情况下，当可利用以上所揭示的技术内容而做出的些许更动、修饰与演变的等同变化，均为本发明的等效实施例；同时，凡依据本发明的实质技术对上述实施例所作的任何等同变化的更动、修饰与演变，均仍属于本发明的技术方案的范围内。
Claims (6)
1.一种肝脏酮体β-羟基丁酸在制备用于诊断急性胰腺炎的诊断试剂中的应用，其特征在于，所述应用在于检测待诊者β-羟基丁酸的血清浓度。
2.一种肝脏酮体β-羟基丁酸在制备用于对急性胰腺炎患者的病情进行监测的诊断试剂中的应用，其特征在于，所述应用在于检测患者β-羟基丁酸的血清浓度。
3.一种基于肝脏酮体β-羟基丁酸在制备用于治疗急性胰腺炎的药物中的应用。
4.如权利要求3所述的一种基于肝脏酮体β-羟基丁酸在制备用于治疗急性胰腺炎的药物中的应用，其特征在于，所述应用包括生酮饮食。
5.如权利要求3所述的一种基于肝脏酮体β-羟基丁酸在制备用于治疗急性胰腺炎的药物中的应用，其特征在于，所述应用包括肠内营养或/和液体复苏时给予β-羟基丁酸或其衍生物/类似物。
6.一种基于肝脏酮体β-羟基丁酸在制备用于预防急性胰腺炎的药物中的应用。
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|---|---|---|---|---|
| CN115068457A (zh) * | 2022-07-04 | 2022-09-20 | 南昌大学第一附属医院 | 短链脂肪酸在制备治疗急性胰腺炎药物中的应用 |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1552315A (zh) * | 1997-03-17 | 2004-12-08 | 英国技术集团国际有限公司 | 治疗组合物 |
| AU2004245567A1 (en) * | 2003-06-03 | 2004-12-16 | Oxford University Innovation Limited | Nutritional supplements and therapeutic compositions comprising (R)-3-hydroxybutyrate derivatives |
| JP2008127369A (ja) * | 2006-11-24 | 2008-06-05 | Nobel Igaku Kenkyusho:Kk | 外分泌障害を処置するための医薬 |
| CN101678090A (zh) * | 2007-03-07 | 2010-03-24 | 乌第有限合伙公司 | 用于预防和治疗自身免疫病的组合物和方法 |
| GB201804548D0 (en) * | 2018-03-21 | 2018-05-02 | Chain Biotechnology Ltd | Pharmaceutical compositions |
| US20180133194A1 (en) * | 2015-06-26 | 2018-05-17 | University Of Florida Research Foundation, Incorporated | Method of treating inflammation using natural compounds and/or diet |
| CN110151774A (zh) * | 2018-02-11 | 2019-08-23 | 四川大学华西医院 | 一种雪菊中黄酮化合物及其药物组合物在制备治疗急性胰腺炎药物中的应用 |
-
2021
- 2021-11-03 CN CN202111296978.3A patent/CN113866399A/zh active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1552315A (zh) * | 1997-03-17 | 2004-12-08 | 英国技术集团国际有限公司 | 治疗组合物 |
| AU2004245567A1 (en) * | 2003-06-03 | 2004-12-16 | Oxford University Innovation Limited | Nutritional supplements and therapeutic compositions comprising (R)-3-hydroxybutyrate derivatives |
| JP2008127369A (ja) * | 2006-11-24 | 2008-06-05 | Nobel Igaku Kenkyusho:Kk | 外分泌障害を処置するための医薬 |
| CN101678090A (zh) * | 2007-03-07 | 2010-03-24 | 乌第有限合伙公司 | 用于预防和治疗自身免疫病的组合物和方法 |
| US20180133194A1 (en) * | 2015-06-26 | 2018-05-17 | University Of Florida Research Foundation, Incorporated | Method of treating inflammation using natural compounds and/or diet |
| CN110151774A (zh) * | 2018-02-11 | 2019-08-23 | 四川大学华西医院 | 一种雪菊中黄酮化合物及其药物组合物在制备治疗急性胰腺炎药物中的应用 |
| GB201804548D0 (en) * | 2018-03-21 | 2018-05-02 | Chain Biotechnology Ltd | Pharmaceutical compositions |
Non-Patent Citations (3)
| Title |
|---|
| HONG XIAO 等: "Identification of potential diagnostic biomarkers of acute pancreatitis by serum metabolomic profiles", PANCREATOLOGY, vol. 17, no. 4, pages 547 - 548 * |
| ŞAHIN E 等: "β-Hydroxybutyrate, One of the Three Main Ketone Bodies, Ameliorates Acute Pancreatitis in Rats by Suppressing the NLRP3 Inflammasome Pathway", TURK J GASTROENTEROL, vol. 32, no. 8 * |
| 江来;万小健;卞金俊;尤新民;: "重症胰腺炎大鼠血液的核磁共振谱代谢组学研究", 上海医学, no. 11, pages 73 - 76 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115068457A (zh) * | 2022-07-04 | 2022-09-20 | 南昌大学第一附属医院 | 短链脂肪酸在制备治疗急性胰腺炎药物中的应用 |
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