糖尿病周围神经病变患者尿代谢组学研究

目的：采用气相色谱-质谱联用技术（GC/MS）技术,分析糖尿病周围神经病变患者尿液中小分子代谢物,为糖尿病周围神经病变的发生机制和早期诊断提供代谢水平上的依据。方法：采用气相色谱-质谱联用技术（GC/MS）检测40例正常人（正常组）、20例单纯糖尿病患者（单纯组）以及40例糖尿病周围神经病变患者（合并组）的尿液样本中小分子代谢物。采用主成分分析法（PCA）和偏最小二乘法判别分析方法（PLS-DA）观察正常组、单纯组以及合并组的代谢谱的变化。结果：正常组和单纯组的代谢谱区分良好,正常组和合并组的代谢谱也能良好的区分。利用Wiley和NIST等数据库筛选和及本实验室建立的标准品代谢物谱库,鉴定了17个与糖尿病周围神经病变密切相关的潜在生物标志物。经过代谢通路分析,糖尿病周围神经病变患者体内存在牛磺酸和亚牛磺酸代谢、甘氨酸、丝氨酸和苏氨酸代谢等代谢异常。结论：糖尿病周围神经病变发生与牛磺酸和亚牛磺酸代谢、甘氨酸,丝氨酸和苏氨酸代谢等代谢异常有关,尿液中鉴定的代谢物有望成为糖尿病周围神经病变诊断的潜在生物标志物。     

慢性阻塞性肺病稳定期模型大鼠支气管肺泡灌洗液的代谢组学研究

目的：基于代谢组学方法研究慢性阻塞性肺病（chronic obstructive pulmonary disease，COPD）稳定期大鼠支气管肺泡灌洗液（bronchoalveolar lavage fluid，BALF）的潜在生物标志物。方法：采用烟熏联合细菌反复感染的方法制备COPD稳定期模型大鼠。采用超高效液相色谱-串联质谱技术采集大鼠的BALF数据，利用多元统计分析软件筛选差异代谢物，再结合数据库鉴定潜在生物标志物，并进行代谢通路分析。结果：多元统计分析结果显示，正常组与模型组BALF代谢物发生显著变化。通过比对数据库，共鉴定出30个差异性代谢物，主要涉及到体内的氨酰基-tRNA的生物合成，甘氨酸、丝氨酸和苏氨酸的代谢，鞘脂代谢，苯丙氨酸代谢和花生四烯酸代谢等8条代谢通路。结论：基于代谢组学研究COPD稳定期的BALF代谢物变化，寻找COPD稳定期相关代谢标志物，为治疗COPD提供理论参考。     

基于气相色谱-质谱联用技术的肥胖儿童血清代谢组学研究

目的：筛选与儿童肥胖相关的血液中差异代谢物,探讨肥胖儿童代谢紊乱的发生机制。方法：采用气相色谱-质谱联用（GC/MS）和模式识别技术分析肥胖儿童血清中代谢物的变化,GC/MS检测25例肥胖儿童（肥胖组）和25例健康儿童（正常组）血清中代谢物,采用偏最小二乘判别分析（partial least squares discrimination analysis,PLS-DA）识别两组样本的血清代谢谱及代谢物。结果：肥胖组和正常组的代谢谱分离良好,肥胖儿童和正常儿童之间的血清代谢成分存在33个差异代谢物,绘制33个差异代谢物ROC曲线,计算曲线下面积,肌酐、马来酸、莽草酸等16个代谢物面积大于0.5,可能是诊断肥胖儿童潜在的生物标志物。结论：肥胖儿童患者血清代谢物的变化机制和甘氨酸,丝氨酸和苏氨酸的代谢、丙氨酸、天冬氨酸和谷氨酸代谢、乙醛酸和二羧酸酯代谢密切相关。     

基于代谢组学研究蚕沙对湿阻中焦证大鼠的“和胃”作用机制

目的：研究蚕沙对湿阻中焦证大鼠粪便及尿液中内源性代谢物的影响,探讨蚕沙治疗湿阻中焦证可能机制。方法：利用"外湿侵体法-游泳力竭法-过食肥甘法"多因素复合法制备湿阻中焦证大鼠模型;采用超高效液相色谱-飞行时间质谱（UPLC-Q-TOF-MS）技术结合多变量统计分析方法,研究湿阻中焦证大鼠粪便和尿液代谢物谱图的变化,确定相关代谢标志物并构建代谢通路。结果：与正常组比较,模型组大鼠粪便及尿液中十八碳-6,9-二烯酸、油酸酰胺、十八碳6烯酸、14,15-二羟基二十碳三烯酸、1-（1Z-十八碳烯基）-sn-甘油、二十四碳五烯酸（C24：5n-6）、7-酮基脱氧胆酸、α-生育三烯酚、溶血磷脂酰乙醇胺（0：0/15：0）、溶血磷脂酰乙醇胺（0：0/18：1（11Z））、溶血磷脂酰胆碱（18：3（6Z,9Z,12Z））、半胱氨酸、硫酸吲哚酚、蓖麻油酸、环磷酸鸟苷显著升高;3-吲哚甲醛、4,6-二羟基喹啉、L-苯丙氨酸、犬尿喹啉酸、α-亚麻酸、甘氨胆酸、2-吲哚羧酸、乙酰磷酸、高香草酸、黄尿酸、棕榈酸、亚油酸、油酸显著降低。同时,蚕沙高、中、低剂量组分别能显著回调其中的17、13、11种代谢物。结论：代谢组学分析揭示蚕沙对湿阻中焦证大鼠具有一定的干预作用,其"和胃"机制可能与调节苯丙氨酸、酪氨酸和色氨酸的生物合成,苯丙氨酸代谢,α-亚麻酸代谢,甘油磷脂代谢,初级胆汁酸的生物合成等有关。     

终末期肾衰竭维持血液透析患者的血清代谢组学研究

目的：采用气相色谱-质谱联用（GC/MS）为基础的代谢组学技术分析终末期肾病（end stage renal disease,ESRD）维持血液透析患者血清中代谢物的变化,筛选出可用于ESRD早期临床诊断的潜在生物标志物,探讨ESRD血液透析患者代谢紊乱的发生机制。方法：采用GC/MS检测63例ESRD患者（病例组）和相匹配的20例健康人（对照组）血清中代谢物,采用偏最小二乘判别分析法（partial least squares discrimination analysis,PLS-DA）分析两组样本血清代谢谱,寻找两组之间的差异代谢物。结果：对照组和病例组的代谢谱区分良好,利用数据库NIST、Wiley Registry代谢组数据库和标准品数据库鉴定出34个差异代谢物,绘制34个差异代谢物ROC曲线,计算曲线下面积,羟胺、尿素、富马酸等28个代谢物面积大于0.5。结论：ESRD患者存在能量代谢、氨基酸代谢、脂质代谢、尿素循环、嘌呤代谢等代谢异常,血清中鉴定的羟胺、尿素、富马酸等28个代谢物有望成为诊断ESRD的潜在生物标志物。     

黄芪甲苷对阿德福韦酯致肾损伤的保护作用和机制研究

目的：本实验旨在研究黄芪甲苷（astragaloside IV,As）对阿德福韦酯（adefovir dipivoxil,Adv）致肾损伤的保护作用,探究其可能的作用机制。方法：将50只SD雄性大鼠按数字表法随机分为正常组（normal）,Adv肾损伤组（30 mg·kg^-1·d^-1）,As低、中、高剂量干预组（10,20,30 mg·kg^-1·d^-1）。通过测定血浆生化指标比较各组肾功能差异;Masson染色评价各组肾小管上皮细胞病理学改变;利用UHPLC-MS代谢组学方法检测各组大鼠血浆内源性代谢物的变化,筛选出差异代谢物。结果：与正常组相比,Adv组肌酐值显著升高,肾损伤严重。而As可显著降低肌酐值和改善肾小管上皮细胞病理学形态,有效干预Adv致肾损伤。Adv组大鼠血浆共发现28个差异代谢物,As可显著逆转16个代谢物的变化。主要涉及与能量代谢相关的苯丙氨酸、酪氨酸和色氨酸代谢通路、泛醌和其他萜烯-醌代谢通路,与氧化应激相关的谷胱甘肽代谢通路。结论：本研究提示As保护Adv致肾损伤的机制与改善细胞供能,减少氧化应激对细胞的损害密切相关。本研究为阿德福韦酯治疗慢性乙型肝炎（CHB）时利用黄芪作为减毒增效的治疗策略提供了基础依据。     

基于代谢组学研究厚朴远志配伍醇提物对尿液代谢物的影响

目的考察厚朴远志配伍对大鼠尿液代谢物的影响,探索其特征生物标志物并分析相关代谢通路,为关联探索厚朴缓解远志胃肠动力障碍的可能机制提供参考。方法 SD♂大鼠40只,随机分为对照组、厚朴3. 50 g·kg~(-1)组、远志1. 75 g·kg~(-1)组、配伍3. 5+1. 75 g·kg~(-1)组,连续灌胃3 d,收集大鼠末次给药24 h内的尿液,采用UPLC-Q-TOF-MS检测各组尿液的代谢物,借助Progenesis QI V2. 0、SIMCA-P14. 0、SPSS 20. 0、Metabo Analyst 3. 0等软件,分析各组尿液代谢标志物及其代谢通路。结果对照组与给药组的代谢物能够明显区分,并筛选出2-氨基苯甲酸、D-葡萄糖醛酸-6,3-内酯、3-甲氧基-4-羟基苯乙醛等16个特征代谢标志物,主要涉及酪氨酸代谢、色氨酸代谢,以及苯丙氨酸、酪氨酸、色氨酸生物合成等通路。结论厚朴可能通过调控酪氨酸代谢、色氨酸代谢、初级胆汁酸生物合成和维生素B_6代谢等代谢通路,缓解远志所致胃肠动力障碍。     

鞣花酸对D-型半乳糖致衰老大鼠干预的尿液代谢组学生物标志物的筛选及代谢通路分析

目的：利用高效液相色谱串联质谱仪（LC-MS）的尿液代谢组学方法,考察鞣花酸对D-型半乳糖致衰老大鼠内源性物质代谢的影响,寻找潜在的生物标志物并分析代谢途径,为研究鞣花酸对D-型半乳糖致衰老大鼠的改善作用及其机制提供理论依据。方法：采用皮下颈静脉注射D-型半乳糖的方法建立氧化衰老大鼠模型,灌胃给予鞣花酸连续8周,收集给药8周24 h尿液,用液相色谱--高分辨质谱对其检测分析;采用主成份分析（PCA）、偏最小二乘法判别分析（PLS-DA）及正交偏最小二乘法判别分析（OPLS-DA）等方法对正常对照组,模型组,阳性对照组,鞣花酸高剂量组、中剂量组、低剂量组6组大鼠尿液代谢物进行聚类分析,筛选出潜在的生物标志物并构建相应的代谢通路。结果：代谢组学分析发现造模后第8周各组大鼠尿液有明显的聚类现象,通过对重要变量的分析鉴定,筛选出12个潜在的生物标志物;涉及的代谢通路包括三羧酸循环、色氨酸代谢、丙酮酸代谢、二元羧酸及牛磺酸代谢等。结论：鞣花酸干预下的D-型半乳糖致衰老大鼠内源性代谢物聚类性趋近正常水平,为进一步阐明鞣花酸对D-型半乳糖致衰老大鼠的作用机制提供依据。     

基于血浆代谢组学评价不同神经保护剂联用方案对缺血性脑卒中生物标志物的影响

目的：通过代谢组学挖掘神经保护剂联用治疗缺血性脑卒中患者血浆的回调性生物标志物,从代谢路径角度评价神经保护剂联用的合理性。方法：通过高效液相色谱与飞行时间质谱（Q-TOF）联用的非靶向代谢组学平台,获取缺血性脑卒中患者的血浆代谢组学数据,用多元变量统计分析进行数据处理,筛选出药物干预后回调的生物标记物及其代谢路径。结果：代谢组学研究表明缺血性脑卒中患者体内主要呈氨基酸、脂类及能量代谢紊乱,给予不同神经保护剂联用方案后整体代谢轮廓回调,经数据库鉴定和匹配后得到两药联用-丁苯酞+依达拉奉组、两药联用-丁苯酞+单唾液酸组和三药联用-丁苯酞+依达拉奉+单唾液酸组显著变化的共性回调生物标记物及特征性回调生物标记物（溶血磷脂酰胆碱18∶0、色氨酸和苹果酸等）。结论：神经保护剂联合应用可使缺血性脑卒中患者的代谢紊乱恢复。调节能量代谢（三羧酸循环）、脂类代谢（甘油磷脂代谢、脂肪酸代谢）和氨基酸代谢（芳香族氨基酸代谢、鸟氨酸代谢）通路等可能是其治疗缺血性脑卒中的神经保护机制。     

基于血浆代谢组学的新生化颗粒对急性血瘀大鼠作用机制研究

目的 研究新生化颗粒对急性血瘀大鼠血浆中内源性代谢物的影响,探讨新生化颗粒治疗急性血瘀证的可能机制。方法 将50只SD大鼠随机分为对照组、模型组、复方丹参滴丸（阳性药,0.10 g·kg^-1）组和新生化颗粒低、高剂量（4.86、9.72 g·kg^-1）组,给药体积10 mL·kg^-1,对照组和模型组大鼠ig给予等体积0.5%羧甲基纤维素钠（CMC-Na）,每天早晚各ig给药1次,共7次。第5次给药后,除对照组外,采用sc盐酸肾上腺素和冰水浴制备大鼠急性血瘀模型。通过测定全血黏度（WBV）、血浆黏度（PV）、活化部分凝血活酶时间（APTT）、凝血酶原时间（PT）、纤维蛋白原（FIB）和凝血酶时间（TT）,观察不同剂量的新生化颗粒对急性血瘀大鼠血液流变学和凝血功能的影响;采用超高效液相色谱-四极杆飞行时间质谱联用（UHPLCQTOF-MS）法检测各组大鼠血浆中的内源性代谢物,通过多变量统计分析筛选潜在生物标志物,结合质谱信息、数据库检索和标准品比对鉴定潜在生物标志物,并将鉴定到的生物标志物导入MetaboAnalyst 5.0数据库推测其可能的代谢通路。结果 与模型组比较,新生化颗粒显著降低急性血瘀大鼠WBV、PV和FIB,显著延长APTT、PT和TT（P＜0.05、0.01）。代谢组学结果显示,从急性血瘀大鼠血浆中共鉴定出21个差异代谢物（准确鉴定7个）,与对照组比较,模型组大鼠血浆中乳酸、肉碱和肌酐等10个内源性代谢物显著上调,苹果酸、琥珀酸和色胺等11个内源性代谢物显著下调（P＜0.05、0.01）;除了硫酸吲哚酚和脱氧胞苷外,新生化颗粒对其他19个生物标志物均有显著回调作用（P＜0.05、0.01）。这些标志物主要涉及苯丙氨酸、酪氨酸和色氨酸生物合成、苯丙氨酸代谢、亚油酸代谢、三羧酸循环和色氨酸代谢。结论 新生化颗粒对急性血瘀大鼠体内紊乱代谢物有较好的回调作用,其作用机制主要与调节苯丙氨酸、酪氨酸和色氨酸生物合成,苯丙氨酸代谢,亚油酸代谢,三羧酸循环和色氨酸代谢通路有关。     

基于尿液代谢组学研究碘克沙醇损伤肾小管功能的作用机制

目的 研究使用碘克沙醇行冠脉造影后肾小管功能出现损伤患者尿液中内源性代谢物的代谢特征，分析碘克沙醇导致肾小管损伤的潜在机制。方法 选择使用碘克沙醇冠脉造影后24 h内肾小管功能正常和肾小管功能出现损伤的患者各50例，分为正常组(n=50)和损伤组(n=50)，收集其造影24 h内的晨尿尿液样本。采用超高效液相色谱串联质谱以及正交偏最小二乘法(orthogonal partial least squares，OPLS-DA)对尿液样品进行代谢分析；利用Metlin、HMDB、KEGG、MetaboAnalyst数据库考察碘克沙醇损伤肾小管功能的代谢特征。结果 鉴定出与碘克沙醇损伤肾小管功能相关的差异代谢物25种[变量权重值(variable important in projection，VIP)>1]，其中有3种代谢差异代谢物的含量显著下降(VIP>1，P<0.05)，分别为L-苯丙氨酸、L-酪氨酸、L-色氨酸。25种差异代谢物涉及的代谢通路有9条，主要为氨基酸代谢，其中Impact>0.10，P<0.05的目标代谢通路有2条，分别为苯丙氨酸、酪氨酸和色氨酸的生物合成通路及苯丙氨酸代谢通路。结论 使用碘克沙醇行冠脉造影后肾小管功能出现损伤患者的尿液代谢主要表现为氨基酸代谢紊乱，尿液中L-酪氨酸、L-苯丙氨酸、L-色氨酸含量显著下降可提示肾小管功能出现损伤。碘克沙醇相关早期肾损伤的发病机制主要是通过影响苯丙氨酸、酪氨酸和色氨酸生物合成通路，苯丙氨酸代谢通路来损伤肾小管，进而影响其功能。     

Effects of oral contraceptives on plasma neutral amino acids and cholesterol during a menstrual cycle

Objective: Concentrations of plasma neutral amino acids, i.e. threonine, serine, asparagine, glycine, alanine, citrulline, α-aminobutyric acid, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, and tryptophan, and serum cholesterol, were determined at the follicular (Day 4), mid-cycle (Day 16) and luteal (Day 25) phases of the menstrual cycle in 15 users of the new generation of combined oral contraceptives (OC), 11 on multiphase combined OC, and 17 controls. Results: The controls showed a decrease in the sum of amino acids to 95% at mid-cycle and 90% in the luteal phase relative to the follicular phase, and a significant decrease in the tyrosine level at the luteal relative to the follicular phase. Since there was no significant difference between the two OC subgroups in the levels of the specified variables at either of the phases, the two groups were considered together. The sum of amino acids in the OC group decreased to 89% at mid-cycle and 91% at the luteal phase relative to the follicular phase, indicating less metabolic effect than reported for older OC formulations. Compared to the controls, the OC group showed significant increased threonine level at the luteal phase, decreased glycine levels at mid-cycle and the luteal phases, decreased citrulline level at mid-cycle, and markedly decreased tyrosine levels at the mid-cycle and luteal phases. Neither total nor high density lipoprotein (HDL) cholesterol differed significantly between the control and OC groups. Conclusion: The results suggest that the metabolic effects of the new generation combined OC on neutral amino acids and cholesterol are only modest to slight, except for the effect on tyrosine, the brain noradrenaline precursor, which may cause disturbances of various noradrenaline-mediated central functions in susceptible subjects.     

Metabolomics combined with serum pharmacochemistry discovering effective compounds of Fangji Huangqi Tang against nephrotic syndrome

OBJECTIVE An integrative strategy was established to discover the effective compounds and their therapeutic targets using Fangji Huangqi Tang(FHT) aiming at inhibiting nephrotic syndrome(NS) as a case study. METHODS The adriamycin-induced nephropathy rat model was evaluated by histopathology analysis and urine protein. The serum biomarkers(pathological marker)related to NS model were characterized by metabolomics, and the metabolites which could be regulated to normal levels after administration with FHT were defined as FHT-regulated biomarkers(effective marker). Moreover, the potential effective compounds were identified by comparison of drug serum between control and model rats. Furthermore, they were further screened based on the correlation analysis between effective marker with the potential effective compounds. At the same time, the potential target of effective ingredients was found by network pharmacology technology. RESULTS The results of serum metabonomics showed that 15 metabolites,including 3-Hydroxybutyric acid, L-phenylalanine and linolenic acid, were associated with renal damage. Among them, 6 effective markers were uric acid, 2-methylbutyrylcarnitine and 10-HDA. Metabolic pathway analysis showed that, phenylalanine, tyrosine and tryptophan biosynthesis, linoleic acid metabolism, phenylalanine metabolism, sphingolipid metabolism were the key pathway associated with NS. The correlation analysis showed that nine constituents such as fan Ghinoline,atractylenolide Ⅲ, cycloastragenol, glycyrrhetinic acid were recognized as effective compounds, whose potential protein targets participated in MAPK signaling pathway,Gn RH signaling pathway and aldoaterone-regulated sodium reabsorption. CONCLUSION This study provides a methodological reference for the study of the efficacy material base of other traditional Chinese medicineand also provides an important basis for the target of FHT against NS.     

蒙药“诃子解草乌毒”减毒存效机理的代谢组学

目的：从代谢组学的角度,采用高效液相与质谱联用的方法研究诃子对于生草乌的"减毒存效"作用机制。方法：将小鼠随机（数字表法）分为空白组、生草乌组、诃子制草乌组、生草乌-诃子3∶1配伍组、生草乌-诃子1∶1配伍组、生草乌-诃子1∶3配伍组、阳性药组,按0.12 g·kg^-1的剂量给药7 d,分别进行棉球肉芽肿试验、二甲苯耳肿胀试验、醋酸扭体试验及热板试,比较每组小鼠肉芽肿胀率、耳肿胀率、扭体次数及舔足潜伏期;将大鼠按以上方法随机分组,按0.12 g·kg^-1的剂量给药4周,通过SIMCA-P软件分析生草乌导致大鼠毒性作用的生物标志物及代谢通路,通过试剂盒检测每组大鼠血清中谷草转氨酶、谷丙转氨酶、肌红蛋白和肌钙蛋白的含量来评估生草乌对大鼠心脏和肝脏的毒性作用。结果：与空白组相比,各实验组都具有明显的抑制肉芽肿胀及耳肿胀效果（P<0.05）,扭体次数明显降低（P<0.05）,舔足潜伏期明显延长（P<0.05）;与阳性药组相比,结果无明显差异;生草乌导致大鼠毒性代谢通路有酰胺tRNA的生物合成,组氨酸代谢,甘氨酸、丝氨酸、苏氨酸代谢,甲烷代谢,乙醛酸和二羧酸代谢,丙氨酸、天冬氨酸、谷氨酸代谢6条代谢通路;生草乌会使大鼠血清中谷草转氨酶、谷丙转氨酶、肌红蛋白和肌钙蛋白的含量明显升高（P<0.05）,诃子可以降低谷草转氨酶、谷丙转氨酶、肌红蛋白和肌钙蛋白的含量。结论：诃子对于生草乌具有"减毒存效"的作用。     

Urinary and Plasma Metabolomics Identify the Distinct Metabolic Profile of Disease State in Chronic Mouse Model of Multiple Sclerosis

Identification of non-invasive biomarkers of disease progression in multiple sclerosis (MS) is critically needed for monitoring the disease progression and for effective therapeutic interventions. Urine is an attractive source for non-invasive biomarkers because it is easily obtained in the clinic. In search of a urine metabolite signature of progression in chronic experimental autoimmune encephalomyelitis (EAE), we profiled urine at the chronic stage of the disease (day 45 post immunization) by global untargeted metabolomics. Using a combination of high-throughput liquid-and-gas chromatography with mass spectrometry, we found 105 metabolites (P < 0.05) significantly altered at the chronic stage, indicating a robust alteration in the urine metabolite profile during disease. Assessment of altered metabolites against the Kyoto Encyclopedia of Genes and Genomes revealed distinct non-overlapping metabolic pathways and revealed phenylalanine-tyrosine and associated metabolism being the most impacted. Combined with previously performed plasma profiling, eight common metabolites were significantly altered in both of the biofluids. Metaboanalyst analysis of these common metabolites revealed that phenylalanine metabolism and Valine, leucine, and isoleucine biosynthetic pathways are central metabolic pathways in both bio-fluids and could be analyzed further, either for the discovery of therapeutics or biomarker development. Overall, our study suggests that urine and plasma metabolomics may contribute to the identification of a distinct metabolic fingerprint of EAE disease discriminating from the healthy control which may aid in the development of an objective non-invasive monitoring method for progressive autoimmune diseases like MS.

Untargeted urinary metabolomics of a chronic mouse model of multiple sclerosis identified Phenylalanine, tyrosine & tryptophan metabolism as the significantly altered metabolic pathway. Eight common metabolites were identified when we combined urinary and plasma metabolic signature, which revealed a perturbation of Phenylalanine metabolism and valine, leucine & isoleucine metabolic pathways, involved in CNS dysfunction during diseases. The identified eight metabolic signature of urine and plasma may be of clinical relevance as potential biomarkers and guide towards the identification of specific metabolic pathways as novel drug targets.

     

2型糖尿病非酒精性脂肪肝患者的代谢相关因素分析

目的 探讨2型糖尿病(T2DM)合并非酒精性脂肪肝(NAFLD)的相关代谢因素.方法 T2DM合并NAFLD组50例和单纯T2DM组30例,所有的受试者均测定各组的人体指标和血代谢指标水平;并分析各指标间及与NAFLD合并症的相关性.结果 (1) T2DM中,合并NAFLD组BMI、WC、TG、ALT、AST较单纯T2DM组明显升高(P＜0.01),差异有统计学意义.(2)在T2DM组,以有无NAFLD为因变量(Y=1,n=0),各指标为自变量,进行多元线性逐步回归分析,BMI、ALT进入回归方程.结论 在T2DM患者中,腹型肥胖、高甘油三脂血症及ALT升高可能是NAFLD发生的危险因素.     

A STUDY ON THE STABILITY OF DIPHENYLINDENONESULPHONYL DERIVATIVES OF AMINO ACIDS TO ACID HYDROLYSIS

The stability of the diphenylindenonesulphonyl (disyl) derivatives of tryptophan, proline, hydroxyproline, histidine, serine, threonine and aspartic acid, as well as of glycine, alanine, α-amino butyric acid, phenylalanine, valine, leucine and isoleucine to acid hydrolysis is studied. The results indicate that the disyl derivatives are much more stable in comparison with the corresponding DNP-and DNS-derivatives. Hence, the dysil-chloride method possesses definite advantages over these widely used methods for determination of N-terminal groups, not only because of its higher sensitivity, but also because of the higher stability of the disyl derivatives of amino acids to acid hydrolysis.