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激光拉曼光谱对血糖含量的分析
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摘要
血糖就是血液中的糖,它在血液中是以葡萄糖的形式存在的。生命体内各组织细胞活动随时都需要能量,葡萄糖就是这些能量的供应者,有了能量的正常供应,生物体的各个组织系统才能健康的运作。所以为了保证生物体内各个器官和组织的能量需要,生物体内血糖必须保持在一定的正常水平。那么当血糖达到什么水平算是正常呢?健康的人早晨的空腹血糖浓度应该在80-120mg%,当空腹血糖浓度低于70mg%我们称之为低血糖,如果空腹时血糖浓度高130mg%,那么这就是高血糖,当空腹血糖浓度超过160-180mg%时,就会有一部分葡萄糖伴随着尿液排出体外,这就是我们常称的糖尿。如果饥饿时间过长或者是持续剧烈体力活动后,低血糖患者的脑组织首先会对低血糖出现头晕、心悸、出冷汗以及饥饿感等反应,如果血糖持续下降到血糖浓度低于45mg%时,就会发生低血糖昏迷的危险现象;一次性或短时间的高血糖对人体没有什么严重的损害,情绪激动、高度紧张或在生物应激状态下可能会出现短暂的高血糖情况,而某一次进食大量的糖类也会引起短暂的高血糖,随后,血糖就慢慢恢复了正常水平,但是长期的高血糖对人体的危害还是很严重的,它会使生物体全身的各个组织和器官发生病变,例如胰腺功能衰竭、抵抗力下降、肾功能受损等等急慢性并发症;糖尿病的患病率特别高,对人生命的危害也是非常严重的,轻者会导致人体某个机能出现问题,重者则有可能致命。糖尿病是一种常见的内分泌代谢性疾病,它是由于生物体内胰岛素分泌的缺陷或者由于胰岛素作用的缺陷引起的持续高血糖为特征的慢性全身代谢疾病。它会带来一些急性慢性并发症,如乳酸性酸中毒,糖尿病酮症酸中毒、糖尿病高渗综合症、微血管并发症以及大血管并发症等等。尽管这些病对我们来说非常恐怖,目前也没有彻底医治的办法,但是我们也不能束手待毙,如果我们能够早期发现或者采取有效的治疗措施,则完全可以达到控制病情、增寿延年的目标,因此血糖的监测对于那些糖尿病和低血糖的患者来说非常重要,通过血糖监测,他们可以掌握自己体内的血糖含量变化,并且通过血糖监测所得数据对他们的饮食、生活规律以及合理用药都有指导意义。当血糖含量不正常时,患者也能够及时发现到医院就医治疗,以避免进一步严重的状况发生。血糖监测还可以用来反映治疗的效果,为治疗方案的调整,改善治疗状况提供数据依据。
     但是,目前血糖的测量方法都是有创或微创的,对于正在接受胰岛素治疗的糖尿病患者来说,每天需要4-7次的血糖检测,而对于低血糖患者和其它有关血糖的并发症者也同样需要频繁的检测血糖来了解体内血糖的含量,如此频繁的血糖监测,对患者造成了身体的疼痛和心灵上的伤害。本文我们探索一种无创的测量血糖含量的方法,为进一步探索临床无创血糖监测方法奠定基础。
     拉曼光谱源于分子的振动和转动能级跃迁,属于分子振动-转动光谱,因此可以获得物质分子结构的直接信息,对物质进行定性分析;试样可通过光纤探头或通过玻璃、石英、蓝宝石窗和光纤直接进行无损测量;拉曼光谱法分辨率高,重现性好,简单快速,并且由于水的拉曼散射极弱,所以拉曼散射法特别适合水体系的研究,尤其是对生物试样和无机物的研究;拉曼光谱谱峰清晰尖锐,峰强度与所测物质活性成分的浓度成正比,据此,可以利用拉曼光谱对生物体的某些成分进行定量分析。
     本文探索一种利用拉曼系统无创的测量血糖的含量的方法,我们首先做了一个体外验证性试验,即拉曼光谱对体外血糖含量的分析。以小白鼠为实验模型,获取小白鼠在注射葡萄糖后不同时间阶段体外血液的拉曼光谱并且探索一种新的数据分析方法,对体外血液光谱的血糖拉曼峰1125cm-1进行分析,结果表明,1125cm-1/1549cm-1的变化对应于血糖的变化,它们之间的线性度达到0.94,这个结果表明了拉曼光谱技术可以对体外血液的血糖含量进行分析。之后,我们利用拉曼系统测量活体小鼠体内的血糖含量,系统的获取了活体小白鼠在注射葡萄糖后不同时间阶段的血液拉曼光谱,对血液光谱1125cm-’的血糖拉曼峰进行分析,发现1125cm-1/1549cm-1的变化同样可以很好的与血糖变化相对应,并且它们之间的线性关系达到了0.98,比体外实验的线性度高,这个原因可能是由于体内实验没有改变血液周围的生理环境,进而得到的生命信息也是最接近自然状态最准确的。文章中的实验表明,拉曼技术可以在无创的条件下分析血糖的含量,这为我们下一步探究临床无创测量血糖方法奠定了理论基础。
Blood glucose is the sugar of blood, which exists as glucose in blood. Every tissue and cellular activities are always in need of energy by glucose. With the supply of energy, all tissue system is possible in normal operation. In order to ensure energy needs of every tissue and cell, blood glucose must be maintained at a certain level. So, what level blood glucose reaches is normal? Blood glucose concentration of healthy man in the morning should be in80-120mg percent before breakfast. When the level blow70mg percent, we call that hypoglycemia and if when the blood glucose concentration is over130mg percent, this phenomenon is known as hyperglycemia. When the blood glucose level exceeds160-180mg percent, there will be a part of glucose with excreted urine, which we call diabetes mellitus. If hungry time is long or sustained vigorous physical activity, hypoglycemia patients appear dizziness, palpitations, sweating and hunger and other reaction. If blood glucose concentration drops continuously to less than45mg percent, there will be hypoglycemia coma risk phenomenon. Disposable or short period of high blood glucose is no serious damage for human body. Excited mood, tense, stress and all can incur transient hyperglycemia situation. Subsequently, it slowly returns to normal level of blood glucose. Long-term hyperglycemia is harm for human. it will incur the organism of the body lesions. For example, pancreatic failure, resistance renal function impairition and other chronic complications. Diabetes mellitus is particularly high and very serious for human life. The light will lead to function problem of the body, serious person may be fatal. Diabetes is a common endocrine and metabolic diseases, it is due to defects of insulin action or the organism endogenous insulin secretion defects, which induce chronic systemic metabolic disease with sustained hyperglycemia. It will bring some of the acute and chronic complications, Such as lactic acidosis, diabetic ketoacidosis, diabetic hyperosmolar syndrome, microvascular complications and so on. Although the disease is very terror to us, we can't fold our hands. If we found the disease early and took effective treatment measures, we could control the disease. Blood glucose monitoring for those patients with diabetes and hypoglycemia is very important. Through the detection of glucose, they can master the change of their blood sugar levels. The data of blood glucose has guiding significance on their diet, patterns of life and the reasonable use of drugs. When the blood glucose level is not normal, patients also find in time to medical treatment in order to avoid the serious situation. Blood glucose monitoring can also be used to reflect the therapeutic effect, and provides data basis for the adjustment of treatment scheme and the condition of treatment.
     However, current blood glucose measurement is a invasive or minimally invasive, for the diabetic patients of receiving insulin treatment, they need4-7times blood glucose detection. As for hypoglycemia and other relevant glucose complications also require frequent monitoring of blood glucose to know the blood glucose level. The blood glucose monitoring is so frequent that patients had bear physical pain and mental damage. In this paper, we explore a noninvasive measurement of blood glucose concentration method, in order to further study the clinical noninvasive glucose monitoring method.
     Raman spectra belong to the molecular vibration spectrum and rotation spectrum derived from molecular vibration and rotation energy level transition. So Raman spectrum could obtain the molecular structure information of the material. The sample can be directly detected nondestructively through the optical fiber probes or glass, quartz, and optical fiber. Raman spectroscopy is high resolution, good reproducibility, simple and rapid and very weak for the Raman scattering of water. So Raman scattering method is particularly suitable for water system, especially for biological specimens and inorganic substance. Raman spectral has clear and sharp peak. The peak intensity and the concentration of active components of measured material are proportional. Accordingly, you can use the Raman spectrum to detect some components of the organism quantitatively.
     This paper explores a noninvasive measurement of blood glucose method with Raman system. Before the vivo test, we first make a confirmatory test in vitro, which is the analysis of Raman spectroscopy of blood glucose. Blood spectrum of rat is measured systematically in vitro after increase of blood glucose caused by injection of glucose to explore an new analysis method. The peak of blood spectrum is analyzed, we also find the intensity change of1125cm-1/1549cm-1also correspond with the change of blood glucose and the linear relationship reaches094. which shows Raman technique can analyze the content of blood sugar quantitatively and provides theoretical basis for measuring blood glucose non-destructively in vivo. Using mice as a mode, blood spectrum of rat is measured systematically in vivo after increase of blood glucose caused by injection of glucose. The peak of blood spectrum is analyzed, we find the intensity change of1125cm-1/1549cm-1also correspond with the change of blood glucose and they have a good linear relationship which reaches098. Our experiment shows the potentiality in measuring blood glucose non-destructively using Raman technique.
引文
[1]伍林,欧阳兆辉,曹淑超,易德莲,秦晓蓉,孙少学,刘峡,拉曼光谱技术的应用及研究进展[J].光散射学报,2005,17(2);180-186
    [2]姚辉璐,朱淼,王桂文,彭立新,何必娟,何敏,黎永青,单个鼻咽癌细胞的拉曼光谱分析的研究[J].光谱学与光谱分析,2007,27(9);1761-1764
    [3]陈五高,激光形成原理[J].高等函授学报(自然科学版),1997第1期;26-29
    [4]陈胜,黄楚云,李默然,生物超微弱发光及其应用[J].黄石理工学院学报,2006,22(4);82-84
    [5]周禾,杨起简,生物发光与生物超微弱发光[J].北京农学院学报,1995,10(2);82-84
    [6]李淑丽,郑新亮,任兆玉,生物超微弱发光研究进展[J].激光杂志,2004,25(4);4-6
    [7]周曼,陈历排,ATP生物发光检测卵巢癌细胞对化疗药物的敏感性[J].广东医学,2000,21(4):293-295
    [8]陈历排,周旻,李志阳,用微量板ATP生物发光法检测肿瘤细胞对化疗药物的敏感性[J].《肿瘤》,2000,20(3);103-105
    [9]马世荣,惠延平,郭双平,程虹,人肝癌HepG2细胞超微弱发光的观察[J].医学研究生学报,2006,19(2);100-103
    [10]吴淑杭,凌云,赵渝,徐亚同,朱文杰,周德平,生物发光在农产品安全性检测中的应用前景[J].农业环境科学学报,2006,25(增刊),421-424
    [11]张菊平,张兴志,巩振辉,超微弱发光在蔬菜研究中的应用[J]Chinese Agricultural Science Bulletin,2006,22(1);220-222
    [12]孙长贵,陈秀枢,生物发光在微生物检验中的应用及研究进展[J].国外医学临床生物化学于检测学分册,1995,16(1);29-32
    [13]谭石慈,邢达,唐永红,李德红,植物叶片超微弱发光光谱研究[J].光子学报,2000,29(11);961-965
    [14]张新华,杨洪强,植物叶绿体和线粒体的超微弱发光[J].植物生理通讯,2004,40(1);111-114
    [15]程海鹏,王君晖,池浩超,朱睦元,豌豆种子萌发过程中超微弱发光的研究[J].浙江大学学报(理学版)2001,28(6);682-685
    [16]高岳,韩鹰,脱水香菇细菌污染的生物发光快速检测试验[J].《现代农业科技》,2007,22:10-12
    [17]张新萍,岳霞丽,胡先文,陈建军,董元彦,水华鱼腥藻超弱发光初探[J].湖北农业科学,2005,2;13-14
    [18]张菊萍,吴清平,李程思,吴慧清,生物发光法微生物快速检测试剂的性质及其影响因素的研究[J].微生物学通报,2006,33(3);36-41
    [19]刘红梅,廖祥儒,吴立峰,蒋继志,热休克对小白未成熟种子萌发、生物发光和抗氧化酶活性的影响[J].食品与生物技术学报,2006,25(3);75-78
    [20]李韶山,王艳,郭周义,朱延彬,包正慷,鲍超,刘颂豪,萌发花生种子超微弱发光的研究[J].光子学报,2000,29(11);966-969
    [21]李德红,邢达,谭石慈,王维江,绿豆和花生的超弱发光[J].植物生理学报,1998,24(2):177-182
    [22]岳伟伟,周爱玉,何保山,罗金平,蔡新霞,基于生物发光技术的细菌总数快速检测仪[J].微纳电子技术,2007,387-390
    [23]于凌春,刘贵忠,张乃琴,X射线和荧光照射对三叶草叶片超微弱发光的影响比较研究[J].安徽农业科学,2008,36(17);7074-7076
    [24]刘铜,高嘉安,陈淑杰,大豆种子超弱发光的研究[J].吉林农业大学学报,1992,14(4);38-41
    [25]鲁文红,何敏,余红平,徐顺清,端粒重复扩增生物发光分析法定量检测端粒酶活性[J].实用医学杂志,2007,23(4);448-451
    [26]高岳,冯敏,王泽港,吕海燕,马飞,史宙亮,葛才林,罗时石,辐照对农产品中细菌ATP生物发光检测的干扰[J].核农学报,2006,21(1)48-51
    [27]叶树明,楼凯凯,杨俊毅,张东声,陈杭,利用ATP生物发光法测定西湖水体微生物量[J].浙江大学学报(农业与生命科学版);500-504
    [28]孟令晶,林漫漫,牛丽媛,刘军贤,王何健,姚辉璐,活体小鼠中单个红细胞的拉曼光谱分析[J].分析化学;39(9),1394-1399
    [29]王桂文,姚辉璐,何必娟,彭立新,黎永青,单个血小板的拉曼光谱分析[J].光谱学与光谱分析,2007,27(7);1347-1350
    [30]王桂文,彭立新,姚辉璐,黎永青,基于光镊与拉曼光谱的红菇担孢子分析[J].激光生物学报,2008,17(2);186-190
    [31]陈秀丽,王桂文,刘军贤,陈萍,黎永青,基于拉曼光谱的地贫红细胞种类识别方法的研究[J].2009,28(4);403-408
    [32]王桂文,姚辉璐,彭立新,何必娟,黎永青,拉曼镊子分析单个苏云金芽孢杆菌伴孢晶体蛋白,分析化学研究简报[J].2007,35(9);1351-1354
    [33]王雁军,姚辉璐,王桂文,汪蕴,丰美福,人肝癌组织细胞的激光光镊拉曼光谱研究,光谱学与光谱分析[J].29(7);1881-1883
    [34]Huilu Yao, Zhanhua Tao, Min Ai, etal. Raman spectroscopic analysis of apoptosis of single human gastric cancer cells[J]. Vibrational Spectroscopy,2009,50(2); 169-324
    [35]梁二军,梁会琴,激光淬火及覆层性能与物相变化的拉曼光谱研究[J].中国激光,2006,33(1);120-123.
    [36]李自达,陶站华,孟令晶等.分选特殊产物微生物的拉曼光谱法[J].光子学报, 2011,40(5);722-727
    [37]姚辉璐,王桂文,何必娟等.单个红细胞的拉曼光谱研究[J].济南大学学报(自然科学版),2005,19(4);328-330.
    [38]李艳,孟令晶,刘军贤等.拉曼光谱法测定单个大米淀粉微粒糊化过程的实时研究[J].光子学报,2010,39(7);1323-1329.
    [39]Annika M. K. Enejder, Thomas G. Scecina, Jeankun Oh, et al. Raman spectroscopy for noninvasive glucose measurements[J]. Journal of Biomedical Optics,2005,10 (3)
    [40]吴小琼,郑建珍,刘文涵等.激光拉曼光谱内标法测定葡萄糖液浓度[J].光谱学与光谱分析,2007,27(7);1344-1346.
    [41]李自达,孟令晶,刘军贤等.拉曼光谱同时测定乙醇和葡萄糖的方法研究[J].分析测试学报,2010,29(11);1145-1148.
    [42]SatishRao, StefanBalint, BenjaminCossins, et al. Raman study of mechanically induced oxygenation state transition of red blood cells using optical tweezers[J]. Biophysical Journal, 2009,96; 209-216.
    [43]Paul I. Okagbare, Francis W. L. Esmonde-White, Steven A. Goldstein, et al. Development of non-invasive Raman spectroscopy for in-vivo evaluation of bone graft osseointegration in a rat model[J].Analyst,2010,135(12); 3142-3146.
    [44]Zhiwei Huang, Seng Khoon Teh, Wei Zheng, et al. Integrated Raman spectroscopy and trimodal wide-field imaging techniques for real-time in vivo tissue Raman measurements at endoscopy[J]. Optics Letters,2009,34(6);758-760.
    [45]Marie Kolling, Kirsty Winkley and Mette von Deden, "For someone who's rich, it's not a problem". Insights from Tanzania on diabetes health-seeking and medical pluralism among Dar es Salaam's urban poor, Globalization and Health 2010,6:8
    [46]Simon C.H. Lam, Joanne W.Y. Chung, K.L. Fan, Thomas K.S. Wong, "Non-invasive blood glucose measurement by near infrared spectroscopy:Machine drift, time drift and physiological effect", IOS Press, Volume 24,Number 6/2010,629-639
    [47]Dong Min Wang, Qi Peng Lu,Li Jun Yao, "Correction of Baseline Drifts due to the Pressure Changes between Attenuated Total Reflection Prism and Human Skin for Noninvasive Blood Glucose Sensing with Fourier Transform Infrared Spectroscopy",Advanced Materials Research,2011(9) 119-123
    [48]Zheng-Ming Chush, Raveendran Paramesran, Kavintheran Thambiratnam, Sin-Chew Poh,' A two-level partial least squares system for non-invasive blood glucose concentration prediction", Chemometrics and Intelligent Laboratory Systems, Volume 104,Issue2,15 December 2010,Pages 347-351
    [49]Yaping Li,Qingbo Li,Guangiun Zhang, "Near-Infrared Spectrophotometric Analysis of Human Blood Glucose:Influence of Repeating Errors on Prediction Accuracy", Spectroscopy,Jun 1.2010
    [50]Narahara Chari Dingari, Ishan Baman, Jeon Woong Kang,Chae-Ryon Kong,Ramachandra R.Dasari and Michael S.Feld, "Wavelength selection-based nonlinear calibration for transcutaneous blood glucose sensing using Raman spectroscopy", J.Biomed.Opt. 16,087009(Aug05,2011);doi:10.1117/1.3611006
    [51]Bongchu Shim, Hyunho Oh, Jeankun Oh, Yongju Yang, Yunhee Ku, Moosub Kim, Hyejjn Eum,Seongmoon Cho, and David R.Miller, "An investigation of the effect of in vivo interferences on Raman glucose measurements", SPIE Digital Library. (2011); doi:10.1117/12.873676
    [52]Yevgeny Beiderman, Raz Blumenberg, Nir Rabani, Mina Teicher, Javier Garcia, Vicente Mico and Zeev Zalevsky, "Demonstration of remote optical measurement configuration that correlates to glucose concentration in blood", Biomedical Optics Express, Vol.2, Issue 4, pp. 858-870(2011)
    [53]V.Ashok, A.Nirmalkumar, and N.Jeyashanthi, "A Novel Method for Blood Glucose Measurement by Noninvasive Technique Using Laser", International Journal of Biological and Medical Sciences.5:12010

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