HbA及热变性HbA的穆斯堡尔谱

<正> 已有某些Hb及其衍生物穆斯堡尔谱的研究。本实验通过对HbA、HbO_2A、及加热后部分热变性的HbO_2A作穆斯堡尔谱测定,以探测Hb辅基上Fe~(2+)的微环境的变化。 材料和方法 一、样品制备     

红细胞外HbA_2与HbA间的相互作用

 1.为了阐明血红蛋白A_2现象的发生机制,研究了红细胞外Hb A_2与HbA有无相互作用。结果表明,这些血红蛋白在离开红细胞后仍能发生相互作用。 2.我们是用交叉电泳来验证这个问题,主要实验结果如下: (1)单向交叉电泳结果表明,溶血液HbA穿过另一溶血液的Hb A_2时,出现明显的交叉电泳图象。 (2)双向交叉电泳实验使上述结果更加明确。 (3)用提纯的Hb A做实验,证实了Hb A与Hb A_2间的相互作用。 (4)血浆白蛋白穿过Hb A_2、Hb A及CA时,没有看到交叉电泳图象。说明Hb A与Hb A_2之间的作用是特异的。 4.初步结论,不仅在缸细胞中Hb A_2是与Hb A结合存在,就是在离开红细胞的条件下,这两种血红蛋白之间仍能发生相互作用。我们认为,这就是血红蛋白A_2现象的发生机制,很可能如此。     

糖化血红蛋白（HbA1c）检测技术与标准化研究进展

糖尿病是世界性疾病,更是严重的公共卫生问题。世界卫生组织（World Health Organization, WHO）将糖化血红蛋白A_1c（glycated hemoglobin A_1c,HbA_1c）确定为糖尿病诊断标准,这对于糖尿病的诊断、监测和治疗具有重要临床意义。近年来,国内外开展了大量有关HbA_1c实验室检测方法与标准化的相关技术研究工作,形成了一系列检测方法和标准体系,取得了一定成果。介绍了具有代表性的HbA_1c实验室检测技术及国内外HbA_1c标准化研究进程,并对当前存在的技术难题进行了分析和展望,以期有助于临床实验室选择合适的检测方法,并推进我国HbA_1c标准化工作的发展。     

HbA1c和FPG水平与2型糖尿病患者视网膜病变的相关性分析

目的：探讨糖化血红蛋（HbA1c）、空腹血糖（FPG）与2型糖尿病患者视网膜病变（DR）的相关性。方法：对我院2010年1月-2012年12月住院或门诊的336例2型糖尿病（T2DM）患者进行眼底检查或眼底血管荧光素造影检测,按有无视网膜病变分为视网膜病变（DR）组和无视网膜病变（NDR）组,并对HbA1c、FBG水平进行检测。结果：DR组较NDR组HbA1c水平高,差异有统计学意义（P〈0．05）,HbA1c水平和DR分期呈正相关（I=0．526,P〈0．001）,而DR组和NDR组FPG水平差异无无统计学意义（P〉0．05）。结论：可将HbA1c作为2型糖尿病患者视网膜病变发生和发展的监测指标之一。     

Differences in the number of embryonic and pseudo-β-globin genes between HbA and HbB sheep

DNA samples obtained from 8 goats, 1 moufflon, and 84 sheep with HbA, HbAB, and HbB belonging to different breeds were digested withBamHI,EcoRI,HindIII andPstI and probed with the 5 end of the goat ^IV- and ^Z-globin genes. Sheep homozygous for HbA show a different restriction pattern than sheep homozygous for HbB with each of these endonucleases. The main differences is that HbB sheep lack the ^H and ^X genes. These results, in addition to those previously obtained using a probe specific for -globin genes, suggest that HbB sheep probably lack the preadult four-gene set. The DNAs from moufflon and sheep homozygous for HbA show indistinguishable restriction patterns. Furthermore, a number of restriction fragment length polymorphisms (RFLPs) are detected in the ^IV and ^Z DNA regions, and oneHindIII RFLP in the ^VI DNA region.This work was supported by the Ministero della Pubblica Istruzione and, in part, by the Consiglio Nazionale delle Ricerche.     

妊娠糖尿病患者血清HbA1c与CRP水平的相关性分析

目的:为明确妊娠期糖尿病(gestational diabetes mellitus,GDM)患者血清糖化血红蛋白(glycosylated hemoglobin,Hb A1c)与C反应蛋白(C-reactive protein,CRP)的关系,本研究检测了GDM患者血糖、血清Hb A1c与CRP水平,并对Hb A1c与CRP的相关性进行了分析。方法:以68例2015年4月至2017年4月于我院诊治的GDM孕妇为研究对象,所有患者均符合《妇产科学》中关于GDM的诊断标准,另选取68例正常孕妇为对照组。采用葡萄糖氧化酶法检测血糖水平(空腹血糖及餐后2 h血糖水平),采用免疫凝集法检测和比较两组血清糖化血红蛋白(HbA1c)水平,采用免疫透射比浊法检测血清C反应蛋白(CRP)水平,并分析HbA1c与CRP的相关性。结果:GDM组患者空腹血糖(fasting plasma glucose,FPG)、2 h血糖(plasma glucose,PG)、血清HbA1c和CRP水平均显著高于正常组(P0.05),GDM患者血清Hb A1c和CRP水平呈显著正相关关系(r=0.654,P0.05)。结论:GDM患者血清HbAlC和CRP水平相较于正常孕妇有显著提高,且二者呈显著的正相关关系,二者联合检测可能作为GDM早期诊断的筛查的重要参考指标。     

牙周炎伴糖尿病患者HbA1c差异性分析及其与口腔龈下菌群分布的关系

目的探讨牙周炎伴糖尿病患者糖化血红蛋白(HbA1c)水平及其与口腔龈下菌群分布的关系。方法将2018年8月至2019年12月本院牙周病科收治的98例慢性牙周炎患者纳入研究,根据是否合并2型糖尿病将患者分为牙周炎组(n=32)和糖尿病组(n=66)。测定和比较2组患者空腹血糖(FBG)、餐后2小时血糖(2hBG)和HbA1c水平,根据HbA1c水平将患者分为轻度组(HbA1c≤7%)(n=26)、中度组(7%10%)(n=18)。利用牙龈指数评估牙周病变程度。取磨牙探诊深度≥4 mm且存在附着丧失位点处龈下菌斑,鉴定菌种种类并计数。结果糖尿病组患者FBG、2hBG和HbA1c水平显著高于牙周炎组(t=2.878,P=0.005;t=9.119,P<0.001;t=3.371,P=0.001)。不同HbA1c水平牙周病变等级分布差异有统计学意义(t=12.364,P=0.002),HbA1c水平与牙龈损伤程度呈正相关(r=0.769,P=0.002)。糖尿病组患者龈下伴放线放线杆菌和二氧化碳嗜纤维菌检出率显著高于牙周炎组(t=3.873,P=0.049;t=14.061,P<0.001)。患者龈下二氧化碳嗜纤维菌、牙龈卟啉单胞菌、中间普氏菌和变黑普氏菌数量随HbA1c水平升高而增加(t=13.914,P<0.001;t=6.985,P=0.002;t=5.955,P=0.004;t=6.808,P=0.002);HbA1c水平与龈下二氧化碳嗜纤维菌、牙龈卟啉单胞菌、中间普氏菌和变黑普氏菌数量呈正相关(r=0.861,P<0.001;r=0.758,P<0.001;r=0.776,P<0.001;r=0.754,P<0.001)。结论牙周炎伴糖尿病患者牙周病变程度及龈下菌群分布变化与HbA1c水平有关,良好的血糖控制有助于维持慢性牙周炎患者龈下菌群稳态,对糖尿病和牙周病预防与治疗具有积极作用。     

基于气相色谱法分析T2DM患者粪便中SCFAs水平与HbA1c的相关性

目的研究2型糖尿病患者粪便中6种短链脂肪酸水平与糖化血红蛋白的相关性。方法采用气相色谱法检测粪便中短链脂肪酸的含量,并对方法学进行考察。选取2018年在本院查体的2型糖尿病患者57例,根据糖化血红蛋白水平将其分为高糖化组(糖化血红蛋白7.0,28例)与低糖化组(糖化血红蛋白≤7.0,29例)。应用气相色谱法检测两组患者粪便中6种短链脂肪酸水平,并分析6种短链脂肪酸水平与糖化血红蛋白的相关性。结果低糖化组患者粪便中乙酸、丙酸、丁酸、戊酸水平显著高于高糖化组(均P0.05),异丁酸与异戊酸水平差异无统计学意义(均P0.05)。Pearson相关性分析结果表明:在2型糖尿病患者中,糖化血红蛋白与粪便中乙酸呈负相关(r=-0.540 1,P0.000 1),与丙酸呈负相关(r=-0.358 1,P=0.006 2),与丁酸呈负相关(r=-0.421 7,P=0.001 1),与戊酸呈负相关(r=-0.326 8,P=0.042 3),与异丁酸、异戊酸无相关性。结论 2型糖尿病患者粪便中短链脂肪酸水平与糖化血红蛋白存在一定的相关性,短链脂肪酸水平的下降可能是影响血糖控制不佳的主要原因。     

Modulating distal cavities in the α and β subunits of human HbA reveals the primary ligand migration pathway

The free volume in the active site of human HbA plays a crucial role in governing the bimolecular rates of O(2), CO, and NO binding, the fraction of geminate ligand recombination, and the rate of NO dioxygenation by the oxygenated complex. We have decreased the size of the distal pocket by mutating Leu(B10), Val(E11), and Leu(G8) to Phe and Trp and that of other more internal cavities by filling them with Xe at high gas pressures. Increasing the size of the B10 side chain reduces bimolecular rates of ligand binding nearly 5000-fold and inhibits CO geminate recombination due to both reduction of the capture volume in the distal pocket and direct steric hindrance of Fe-ligand bond formation. Phe and Trp(E11) mutations also cause a decrease in distal pocket volume but, at the same time, increase access to the Fe atom because of the loss of the γ2 CH(3) group of the native Val(E11) side chain. The net result of these E11 substitutions is a dramatic increase in the rate of geminate recombination because dissociated CO is sequestered close to the Fe atom and can rapidly rebind without steric resistance. However, the bimolecular rate constants for binding of ligand to the Phe and Trp(E11) mutants are decreased 5-30-fold, because of a smaller capture volume. Geminate and bimolecular kinetic parameters for Phe and Trp(G8) mutants are similar to those for the native HbA subunits because the aromatic rings at this position cause little change in distal pocket volume and because ligands do not move past this position into the globin interior of wild-type HbA subunits. The latter conclusion is verified by the observation that Xe binding to the α and β Hb subunits has little effect on either geminate or bimolecular ligand rebinding. All of these experimental results argue strongly against alternative ligand migration pathways that involve movements through the protein interior in HbA. Instead, ligands appear to enter through the His(E7) gate and are captured directly in the distal cavity.     

不同孕期GDM孕妇CRP水平、HbA1c和维生素B12相关性研究

摘要 目的：对不同孕期妊娠期糖尿病(gestational diabetes mellitus,GDM)孕妇的全血C反应蛋白(C-reactive protein,CRP)水平、糖化血红蛋白(glycosylated hemoglobin,Hb A1c)和血清维生素B12水平进行检测,并对其相关性进行分析。方法：以妊娠期孕妇为研究对象,根据OGTT试验结果分为对照组和研究组,对照组为健康孕妇,研究组为GDM孕妇,对两组中孕期和晚孕期孕妇的全血CRP、HbA1c和血清维生素B12进行检测。结果：研究组中孕期和晚孕期GDM的全血CRP和HbA1c水平均显著高于对照组（P＜0.05）。与中孕期相比,两组晚孕期全血CRP水平均无明显变化(P＞0.05),对照组孕妇全血HbA1c水平无明显变化(P＞0.05),而研究组晚孕期全血HbA1c水平显著升高(P＜0.05)。与对照组相比,研究组中孕期和晚孕期的血清维生素B12水平显著降低(P＜0.05);与中孕期相比,对照组孕妇血清维生素B12水平无明显变化(P＞0.05),而研究组晚孕期血清维生素B12水平显著降低(P＜0.05)。研究组中孕期和晚孕期CRP水平与HbA1c呈显著的正相关,与维生素B12呈显著的负相关(P＜0.05)。正常孕妇中孕期和晚孕期的CRP水平和HbA1c、维生素B12水平均未呈现相关性（P＞0.05）。结论：GDM孕妇中孕期和晚孕期的全血CRP、HbA1c和血清维生素B12均存在异常,且CRP水平与HbA1c显著正相关,与维生素B12水平显著负相关。     

糖尿病性视网膜病变术后CRT、SFCT、mALB、MBG、HbA1c水平的变化及相关性

本研究通过观察糖尿病性视网膜病变术后患者黄斑中心凹视网膜厚度,脉络膜厚度,尿微量白蛋白、血糖、糖化血红蛋白的水平,试图了解其差异及相关性。我们选取2016年1月至2017年12月于我院就诊的糖尿病性视网膜病变患者200例,根据其有无视网膜病变、有无肾病、术后有无黄斑水肿分为合并组和未合并组,同时选取100例正常成年人作为对照。观察糖尿病患者和对照组、未合并和合并并发症糖尿病患者的黄斑中心凹视网膜厚度(central retinal thickness, CRT),凹下脉络膜厚度(subfoveal choroidal thickness,SFCT),尿微量白蛋白(microAlbunminuria, mALB)、平均血糖(mean blood glucose, MBG)和糖化血红蛋白(glycated haemoglobin, HbA1c)水平,进一步分析了糖尿病黄斑水肿患者的尿微量白蛋白水平与黄斑中心凹视网膜厚度、脉络膜厚度、血糖、糖化血红蛋白的相关性。研究结果表明,糖尿病组患者的CRT水平较对照组低,SFCT、mALB、MBG和HbA1c水平高于对照组;合并视网膜病变、合并肾病和合并黄斑水肿组患者的CRT水平较未合并组低,SFCT、mALB、MBG和HbA1c水平均高于未合并组;黄斑水肿患者的m ALB水平与CRT水平负相关,与SFCT、MBG和HbA1c水平正相关。本研究得出结论:糖尿病性视网膜病变术后患者黄斑中心凹视网膜厚度(CRT)较薄,脉络膜厚度(SFCT)变厚,且与尿微量白蛋白密切相关。     

血红蛋白A_2现象发生机制的研究——“红细胞HbA_2”为HbA_2与HbA的结合产物

为了弄清血红蛋白A_2现象的发生机制,我们对“红细胞HbA_2”的化学组成进行了分析。“红细胞HbA_2”的双向电泳结果表明,它含有两种血红蛋白成分:一种相当于HbA,另一种很可能是溶血液HbA_2。其单向二次电泳结果也证明,它是由溶血液HbA_2和HbA所组成。结果初步说明,盘红细胞中HbA_2可能与HbA结合存在。两者可能有相互作用,也许这是产生血红蛋白A_2现象的原因。     

Isolated Hb Providence β82Asn and β82Asp fractions are more stable than native HbA(0) under oxidative stress conditions

We have previously shown that hydrogen peroxide (H(2)O(2)) triggers irreversible oxidation of amino acids exclusive to the β-chains of purified human hemoglobin (HbAo). However, it is not clear, whether α- or β-subunit Hb variants exhibit different oxidative resistance to H(2)O(2) when compared to their native HbAo. Hb Providence contains two β-subunit variants with single amino acid mutations at βLys82→Asp (βK82D) and at βLys82→Asn (βK82N) positions and binds oxygen at lower affinity than wild type HbA. We have separated Hb Providence into its 3 component fractions, and contrasted oxidative reactions of its β-mutant fractions with HbAo. Relative to HbAo, both βK82N and βK82D fractions showed similar autoxidation kinetics and similar initial oxidation reaction rates with H(2)O(2). However, a more profound pattern of changes was seen in HbAo than in the two Providence fractions. The structural changes in HbAo include a collapse of β-subunits, and α-α dimer formation in the presence of excess H(2)O(2). Mass spectrometric and amino acid analysis revealed that βCys93 and βCys112 were oxidized in the HbAo fraction, consistent with oxidative pathways driven by a ferrylHb and its protein radical. These amino acids were oxidized at a lesser extent in βK82D fraction. While the 3 isolated components of Hb Providence exhibited similar ligand binding and oxidation reaction kinetics, the variant fractions were more effective in consuming H(2)O(2) and safely internalizing radicals through the ferric/ferryl pseudoperoxidase cycle.     

HbA1c Levels Are Associated with Chronic Kidney Disease in a Non-Diabetic Adult Population: A Nationwide Survey (KNHANES 2011–2013)

Background

Many studies have reported an association between glycated hemoglobin A1c (HbA1c) and metabolic syndrome (MetS) in non-diabetes patients. Each component of MetS is in fact related to chronic kidney disease (CKD) incidence and progression. Therefore, HbA1c in non-diabetic mellitus (DM) may be intrinsically associated with the prevalence of CKD. The hypothesis of the present study was that high HbA1c in non-DM patients is associated with CKD.

Patients and Methods

The total number of participants in this study was 24,594. The participants were divided into three groups according to their HbA1c levels: a Low group (<5.7% or <39 mmol/mol), a Middle group (5.7–6.0% or 39–42 mmol/mol), and a High group (>6.0% or >42 mmol/mol). The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation.

Results

The number of participants allocated to the Low, Middle, and High groups was 8,651, 4,634, and 1,387, respectively. Linear regression analyses were performed to evaluate the association between variables. Standardized β ± standard error was 0.25 ± 0.22 for waist circumference, 0.44 ± 0.20 for fasting glucose, –0.14 ± 0.30 for high-density lipoprotein cholesterol levels, 0.15 ± 2.31 for triglyceride levels, 0.21 ± 0.00 for systolic blood pressure, 0.10 ± 0.00 for diastolic blood pressure, and –0.22 ± 0.42 for eGFR (P < 0.001 for all variables). eGFR in non-diabetes participants was inversely associated with the HbA1c level, where eGFR decreased as HbA1c levels increased. Standardized βs were –0.04 ± 0.42 in multivariable analysis (P < 0.001). The proportion of participants with only MetS, only CKD, or both MetS and CKD was higher in the High group than in the Low and Middle groups.

Conclusion

High HbA1c in non-DM patients may be associated with CKD. Renal function in patients with high HbA1c levels may need to be monitored.     

糖尿病合并急性心肌梗死患者PCI术后造影剂肾病的危险因素及SHI、HbA1c的预测价值研究

摘要 目的：探讨糖尿病合并急性心肌梗死（AMI）患者经皮冠状动脉介入治疗（PCI）术后造影剂肾病（CIN）的危险因素,并分析应激性高血糖指数（SHI）和糖化血红蛋白（HbA1c）对CIN的预测价值。方法：选取2019年1月～2022年1月我院收治的102例接受PCI治疗的糖尿病合并AMI患者,根据PCI术后是否发生CIN分为CIN组26例和非CIN组76例。收集患者基线资料和计算SHI,采用单因素和多因素Logistic回归分析糖尿病合并AMI患者PCI术后CIN的影响因素,受试者工作特征（ROC）曲线分析SHI、HbA1c对糖尿病合并AMI患者PCI术后CIN的预测价值。结果：单因素分析显示,CIN组年龄大于非CIN组,高血压比例、Killip分级≥Ⅱ级比例和心肌肌钙蛋白T、N末端B型利钠肽前体（NT-proBNP）、超敏C反应蛋白（hs-CRP）、血糖、HbA1c、血尿酸、血尿素氮、血肌酐、SHI高于非CIN组,淋巴细胞计数、白蛋白、估算肾小球滤过率（eGFR）低于非CIN组（P＜0.05）。多因素Logistic回归分析显示,年龄增加、高血压、Killip分级≥Ⅱ级、NT-proBNP升高、白蛋白降低、hs-CRP升高、HbA1c升高、血肌酐升高、eGFR降低、SHI升高为糖尿病合并AMI患者PCI术后CIN的独立危险因素（均P＜0.05）。ROC曲线分析显示,SHI、HbA1c联合预测糖尿病合并AMI患者PCI术后CIN的曲线下面积大于两者单独预测的曲线下面积。结论：年龄增加、高血压、Killip分级≥Ⅱ级、NT-proBNP、hs-CRP、HbA1c、血肌酐、SHI升高及白蛋白、eGFR降低为糖尿病合并AMI患者PCI术后CIN的独立危险因素,SHI联合HbA1c对糖尿病合并AMI患者PCI术后CIN的预测价值较高。