瓜氨酸、肠型脂肪酸结合蛋白、肠三叶因子在儿童危重症急性胃肠损伤诊断中的作用

目的比较血清瓜氨酸、肠型脂肪酸结合蛋白(IFABP)和肠三叶因子(ITF)在儿童危重症急性胃肠损伤诊断中的价值。方法入选84例危重症患儿,应用高效液相色谱法检测血清瓜氨酸,酶联免疫吸附法检测血清IFABP、ITF,结合临床资料进行比较分析。结果胃肠损伤组血清瓜氨酸水平低于非胃肠损伤组,血清IFABP、ITF水平高于非胃肠损伤组,差异有统计学意义(P均0.05);危重症患儿血清瓜氨酸与反应蛋白(CRP)、降钙素原(PCT)、住院时间呈显著负相关(r=-0.36~-0.31,P均0.01)。结论血清瓜氨酸、IFABP、ITF对危重症患儿急性胃肠损伤均有一定的诊断价值,瓜氨酸水平可能反映危重病患儿胃肠损伤程度。     

肠型脂肪酸结合蛋白在早期诊断小儿肠缺血性疾病中的研究进展

肠道缺血性疾病是一种严重的临床急症,由于在缺血的可逆转期缺少有效的诊断方法,患者往往因此而错失治疗的最佳时机,造成严重而复杂的并发症.临床医师迫切需要可用于早期诊断的生物学指标.肠型脂肪酸结合蛋白(I-FABP)是由小肠单层柱状上皮细胞分泌的一种蛋白质,具有较好的器官特异性.研究发现血和尿中I-FABP是早期诊断肠缺血很好的指标.现就I-FABP的基因、结构、功能、代谢特点及其在早期诊断小儿肠缺血性疾病中的应用和研究进展作一综述.     

Serum intestinal fatty acid binding protein level for early diagnosis and prediction of severity of necrotizing enterocolitis

Background/Aim

Intestinal fatty acid binding protein (I-FABP) is found within cells at the tip of the intestinal villi, an area commonly injured in necrotizing enterocolitis (NEC). In this study, we aimed to investigate the value of serum I-FABP in early diagnosis and predicting severity of NEC.

Methods

This prospective study was conducted between April 2009 and November 2009. The preterm infants with suspected NEC were included in the study. These infants were divided into two groups according to their final diagnoses; Group 1: Stage 1 NEC and Group 2: Stages 2–3 NEC (Group 2a: Stage 2 NEC, Group 2b: Stage 3 NEC). Healthy preterms were assigned to control group (Group 3). Serial blood samples were obtained from the patients at symptom onset, 24 h and 72 h later. One blood sample was taken from the controls. Serum I-FABP levels were compared among the groups.

Results

Initial serum I-FABP concentrations were 324.0 ± 165.8 pg/ml, 764.7 ± 465.1 pg/ml, and 360.2 ± 439.5 pg/ml in Group 1, Group 2a, and Group 2b, respectively, and all were significantly higher than those of the control group (76.9 ± 115.9 pg/ml) (p < 0.001). The serum I-FABP levels gradually decreased from the onset of the disease to 72nd hour in Group 1 and Group 2a (p = 0.001). In Group 2b I-FABP concentrations slightly decreased at 24th hour of the disease and increased thereafter, but the difference was not significant (p = 0.06).

Conclusion

Serial measurements of I-FABP levels may be a useful marker for early diagnosis and prediction of disease severity in NEC.     

肠脂肪酸结合蛋白在肺炎合并胃肠功能损伤患儿血清中的变化及意义

目的探讨肠脂肪酸结合蛋白 （IFABP）在社区获得性肺炎患儿血清中的变化及与胃肠功能损伤的相关性。方法选择2015年1月至10月的社区获得性肺炎患儿82例 （轻症34例,重症48例）,根据小儿危重病例评分 （PCIS）将重症肺炎患儿分为非危重组 （25例）和危重组 （23例）;另选取体检的健康儿童30例作为对照组。采用酶联免疫吸附法检测血清IFABP浓度,并对重症肺炎患儿进行急性胃肠损伤 （AGI）分级。比较各组间血清IFABP浓度的差异,并对IFABP与AGI分级和PCIS进行相关性分析。结果重症肺炎血清IFABP浓度均高于对照组和轻症肺炎组 （均P <0.01）,轻度肺炎组血清IFABP浓度亦明显高于对照组 （P <0.01）。危重组血清IFABP浓度高于非危重组 （P <0.01）。AGI1~4级组血清IFABP均高于对照组 （P <0.01）,而且随着AGI级别的增高,血清IFABP浓度也逐渐增高,差异有统计学意义 （P <0.01）。IFABP与AGI分级呈正相关 （P <0.01）;与PCIS呈负相关 （P <0.01）。结论肺炎患儿血清IFABP均有所增高,血清IFABP可以作为肺炎患儿合并胃肠损伤早期诊断和病情评估的敏感指标。     

新生儿坏死性小肠结肠炎血浆肠脂肪酸结合蛋白水平变化的意义

目的 探讨血浆肠脂肪酸结合蛋白（I-FABP）水平变化在指导新生儿坏死性小肠结肠炎（NEC）诊断及治疗中的意义.方法 选择2011年5月至2012年12月我院新生儿科收治的患儿,按入院先后顺序,以明确诊断NEC的50例新生儿为NEC组,其中NECⅡ期30例,NECⅢ期20例,以非NEC新生儿50例为对照组.NEC组在确诊后24 h内、对照组在相应日龄取血,采用酶联免疫吸附法（ELISA）检测血浆I-FABP水平,根据NEC患儿病情转归分为存活组及病死组,按治疗方法分为保守治疗组和手术治疗组,比较不同组间血浆I-FABP水平、新生儿危重病例评分（NCIS）分值、脓毒症的发生率及病死率.结果 NECⅡ期组、NECⅢ期组和对照组血浆I-FABP水平分别为（95.6±18.5） μmol/L、（151.2±10.8）μmol/L和（1.2±2.3）μmol/L,组间比较差异有统计学意义（P＜0.05）;NECⅡ期组和NECⅢ期组NCIS评分明显低于对照组,脓毒症发生率和病死率均高于对照组,差异有统计学意义（P＜0.05）,NECⅡ期组和NECⅢ期组差异无统计学意义（P＞0.05）.病死组血浆I-FABP水平、脓毒症发生率高于存活组,NCIS评分低于存活组;保守治疗组I-FABP水平低于手术治疗组,NCIS评分高于手术治疗组,差异均有统计学意义（P＜0.05）.结论 血浆I-FABP水平可较敏感地反映NEC患儿的病情变化,可作为预测NEC病情严重程度及指导采取内外科治疗的指标之一.     

亚低温治疗窒息新生儿二胺氧化酶及肠脂肪酸结合蛋白的变化及意义

目的：观察选择性头部亚低温治疗窒息新生儿中二胺氧化酶(diamine oxidase,DAO)及肠脂肪酸结合蛋白(intestinal fatty acid binding protein,I-FABP)水平的变化。方法选取2013年6月至2014年12月在河北省保定市妇幼保健院NICU住院的重度窒息患儿60例,随机分为常规治疗组和亚低温治疗组,同时选取同期住院的除外缺血缺氧及胃肠功能障碍相关疾病的新生儿30例作为对照组。分别在入院时、治疗7d后采集静脉血,收集血清应用ELISA法检测DAO、I-FABP水平,同时对患儿进行胃肠功能障碍评分。结果入院时亚低温治疗组及常规治疗组患儿DAO、I-FABP水平比较差异无统计学意义[DAO：(15.77±2.04)U/ml,(15.81±1.85)U/ml,P ﹥0.05;I-FABP：(310.01±46.43)ng/L,(301.12±38.61)ng/L,P ﹥0.05],但较对照组均升高[(7.65±0.74)U/ml,(51.65±6.91)ng/L];治疗7d后,两组患儿DAO、I-FABP 水平较入院时均减低[DAO：(7.88±1.87)U/ml,(12.51±1.53)U/ml;I-FABP：(59.16±6.17)ng/L,(121.31±21.54)ng/L],亚低温治疗组下降明显,差异有统计学意义(P﹤0.05),且DAO及I-FABP水平与胃肠功能障碍评分呈正相关(r1=0.831, r2=0.827,P﹤0.01)。结论选择性头部亚低温治疗可使DAO、I-FABP水平下降,提示其在一定程度上利于受损胃肠功能的恢复。     

Expression pattern of fatty acid transport protein-1 (FATP-1), FATP-4 and heart-fatty acid binding protein (H-FABP) genes in human term placenta

Placental tissue from five women undergoing elective caesarean did not present differences in fatty acids or mRNA expression of FATP-1, FATP-4 and H-FABP in different placental locations. mRNA expression of FATP-1 and FATP-4 was significantly higher than H-FABP. The expression of L-FABP was too low in placenta for accurate quantification.     

Early onset of fatty liver in growth-restricted rat fetuses and newborns

Intrauterine growth-restricted (IUGR) newborns have increased risk of adult metabolic syndrome, including fatty liver. However, it is unclear whether the fatty liver development is "programmed" or secondary to the accompanying obesity. In this study, we examined hepatic lipid accumulation and lipid-regulatory factors (sterol regulatory element-binding protein-1c and fatty acid synthase) in IUGR and Control fetal (embryonic day 20; e20) and newborn (postnatal day 1; p1) rat pups. Notably, despite of in utero undernutrition state, IUGR fetuses demonstrated "fatty liver" with upregulation of these lipogenic indices at as early as e20. Both IUGR and Control newborns exhibited the same extent of massive increase in hepatic lipid content, whereas IUGR newborns continued to exhibit upregulated lipogenic indices. The persistent upregulation of the lipogenic indices in fetal and newborn IUGR suggests that fatty liver is gestationally programmed. Our study suggested that IUGR offspring were born with an altered metabolic life strategy of increased fuel/lipid storage which could be a distinct metabolic pathway of the thrifty phenotype.     

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??Objective??To investigate the value of serum intestinal fatty acid binding protein??I-FABP?? and serum amyloid A??SAA?? in the diagnosis of necrotizing enterocolitis??NEC??in the newborn. Methods??Fifty-six preterm infants with a confirmed diagnosis of NEC from October 2014 to October 2015 were recruited as case group??stage??26 cases??stage??/??30 cases??. Thirty children diagnosed with non-digestive diseases in the same period were recruited as the control group. Serum levels of I-FABP and SAA were determined by enzyme-linked immunosorbent assay.The diagnostic value of I-FABP and SAA for severe NEC was assessed using the receiver operating characteristic??ROC??curve. Results??Stage??/?? cases in the case group had significantly higher serum I-FABP levels and SAA levels than the control group and Stage??cases??P??0.05??. The area under the ROC curve for serum I-FABP was 0.80??95%CI??0.69-0.92????with the optimal cut-off point of 21.8 μg/L. Under this cut-off point??the sensitivity and specificity were 70.0%and 81.0%??respectively. The area under the ROC curve for SAA was 0.76??95%CI??0.63-0.89????with the optimal cut-off point of 1657.8 μg/L. Under this cut-off point??the sensitivity and specificity were 67.0% and 80.0%??respectively. Conclusion??In newborn infants with NEC??serum I-FABP and SAA l can be used as biomarkers for the diagnosis of severe NEC.     

Circulating adipocyte fatty acid binding protein levels in healthy preterm infants: Positive correlation with weight gain and total-cholesterol levels

Background

Adipocyte fatty acid binding protein (a-FABP) has been suggested to play an important role in the pathogenesis of metabolic syndrome. Preterm infants are at risk for the later development of insulin resistance, and, possibly, other components of metabolic syndrome.

Aim

To determine circulating levels of a-FABP in preterm infants and examine possible associations of a-FABP with metabolic indices (serum lipids, glucose, and insulin levels, and homeostasis model assessment index of insulin resistance [HOMA-IR]), levels of leptin and adiponectin, anthropometric parameters and weight gain.

Study design

Prospective cohort study.

Subjects

55 healthy preterm (mean [SD] gestational age 32.8 [1.8] weeks) and 23 fullterm infants (reference group).

Outcome measures

Serum a-FABP, lipids, glucose, insulin, leptin and adiponectin levels at 31.9 [10.4] days of life.

Results

Serum a-FABP levels did not differ significantly between preterm and fullterm infants. A-FABP levels correlated positively with total-cholesterol [total-C] in both preterm and fullterm infants (β = 0.33; p = 0.01 and β = 0.33; p = 0.04, respectively). In addition to total-C, weight gain correlated independently with a-FABP levels in preterm infants (β = 0.36, p = 0.01).

Conclusions

An association between a-FABP levels and indices of insulin resistance was not present in infants studied. As the development of insulin resistance in children born prematurely is possibly associated with weight gain in early postnatal life, follow-up of our study population is necessary to demonstrate whether a-FABP levels, shown to correlate with weight gain in preterm infants, are a predictive marker for the later development of insulin resistance in these infants.     

Faecal short-chain fatty acids in breast-fed and bottle-fed infants

Faecal short-chain fatty acids (SCFAs) were determined in 49 infants on three occasions, i.e. at ages three and six days and two months. At two months, the breast-fed infants had a significantly higher proportion of acetic acid in the SCFA spectra than the bottle-fed infants. The data suggest that the composition of the intestinal microflora in most breast-fed infants is characterized by a high relative content of acetic acid in faecal SCFAs. This may be associated with protection against diarrhoea and respiratory infections in the infant.     

胰岛素样生长因子结合蛋白6在维甲酸诱导的大鼠马蹄内翻足畸形中的表达研究

目的 探讨大鼠先天性马蹄内翻足(CCF)软骨组织内胰岛素样生长因子结合蛋白6(IGFBP-6)的表达规律.方法 应用生物学活性物质全反式维甲酸(ATRA)构建大鼠CCF动物模型;光镜和透射电镜观测大鼠的足部软骨组织病理学改变;RT-PCR及Western印迹杂交检测胎鼠足部软骨组织中IGFBP-6 mRNA及蛋白质的表达水平.结果 120 mg/kg的ATRA诱导实验组35%的胎鼠出现CCF畸形,其他畸形包括:内翻足、小脑畸形、腭裂、无尾畸形等;在骨骼畸形胎鼠的足部距骨内软骨发生中心带缩小,软骨细胞数量减少,软骨细胞核内粗面内质网扩张,线粒体嵴紊乱;正常胎鼠软骨组织内IGFBP-6基因呈低水平表达状态,而骨骼畸形胎鼠IGFBP-6的mRNA和蛋白质表达则明显升高300%和197%(P＜0.05).结论 正常大鼠软骨组织内IGFBP-6基因有低表达.CCF大鼠软骨组织内IGFBP-6的高表达可能与骨骼发育畸形的发生密切相关.     

脂肪型脂肪酸结合蛋白在早产大鼠高氧肺损伤时的表达

目的 观察脂肪型脂肪酸结合蛋白4(FABP4)在早产大鼠高氧肺损伤时肺组织及支气管肺泡灌洗液(BALF)中的表达,探讨其与新型支气管肺发育不良(BPD)发病机制之间的关系.方法 早产大鼠生后6 h 内随机分为高氧组和对照组,对照组置于常压空气中,高氧组置于浓度为60% 的高氧舱中,两组均于出生后第3 天(P3)、第7 天(P7)和第14 天(P14)各随机取8 只大鼠,采用免疫组织化学方法和逆转录-聚合酶链反应技术检测不同时间两组肺组织FABP4 蛋白及mRNA 表达水平,应用ELISA 方法检测BALF中FABP4 的含量.结果 FABP4 主要在肺泡巨噬细胞、支气管上皮细胞和血管内皮细胞表达.两组FABP4 蛋白和mRNA 在肺组织中的表达以及两组BALF 中FABP4 的含量均随鼠龄递增呈逐渐增加的趋势,至P14 时最高.高氧组肺组织中FABP4 mRNA 的表达在P7、P14,FABP4 蛋白的表达在P3、P7 及P14 时均高于对照组(均P<0.05);高氧组BALF 中FABP4 的含量在P7、P14 时均高于对照组(均P<0.05).结论 高氧肺损伤时FABP4 表达升高,可能是引起肺微血管发育障碍及肺泡化进程受阻,进而导致新型BPD 发生的重要因素.     

HSD17B4基因突变致D-双功能蛋白缺乏症

15 d男性患儿,因反复抽搐14 d入院。主要临床表现为难治性癫痫发作、反应差、喂养困难、四肢肌张力低、双侧听力受损,神经电生理表现为双侧脑干听觉诱发电位减弱及脑电图爆发-抑制图形,血清极长链脂肪酸提示二十六烷酸显著增高,基因检测提示HSD17B4基因c.101C>T(p.Ala34Val),c.1448_1460del(p.Ala483Aspfs*37)复合杂合突变。该文报道1例HSD17B4基因突变所致D-双功能蛋白缺乏症,对该病流行病学、临床特征及诊疗进行归纳总结,重点关注与大田原综合征的鉴别,为该病早期诊断提供了参考依据。