脓毒症急性胃肠损伤评估的研究进展

近年来,胃肠道作为脓毒症病理生理过程中最早和最严重受累的器官之一,其重要性逐渐被人们认识。早期、客观、及时、准确的评估脓毒症患者的急性胃肠损伤程度,及早进行干预,可减轻由其诱发的失控性炎性反应,改善脓毒症患者的预后。目前,临床上对脓毒症急性胃肠损伤仍缺乏特异性的诊断指标或体系。为此,作者总结了近几年脓毒症急性胃肠损伤的评分及分级系统、血清生物学标志物的研究进展,为脓毒症急性胃肠损伤的早期诊断及治疗提供一定的参考依据。     

Relative contribution of different l-arginine sources to the substrate supply of endothelial nitric oxide synthase

In certain cases of endothelial dysfunction l-arginine becomes rate-limiting for NO synthesis in spite of sufficiently high plasma concentrations of the amino acid. To better understand this phenomenon, we investigated routes of substrate supply to endothelial nitric oxide synthase (eNOS). Our previous data with human umbilical vein (HUVEC) and EA.hy.926 endothelial cells demonstrated that eNOS can obtain its substrate from the conversion of l-citrulline to l-arginine and from protein breakdown. In the present study, we determined the quantitative contribution of proteasomal and lysosomal protein degradation and investigated to what extent extracellular peptides and l-citrulline can provide substrate to eNOS. The RFL-6 reporter cell assay was used to measure eNOS activity in human EA.hy926 endothelial cells. Individual proteasome and lysosome inhibition reduced eNOS activity in EA.hy926 cells only slightly. However, the combined inhibition had a pronounced reducing effect. eNOS activity was fully restored by supplementing either l-citrulline or l-arginine-containing dipeptides. Histidine prevented the restoration of eNOS activity by the dipeptide, suggesting that a transporter accepting both, peptides and histidine, mediates the uptake of the extracellular peptide. In fact, the peptide and histidine transporter PHT1 was expressed in EA.hy926 cells and HUVECs (qRT/PCR). Our study thus demonstrates that l-citrulline and l-arginine-containing peptides derived from either intracellular protein breakdown or from the extracellular space seem to be good substrate sources for eNOS.     

大黄鼻饲、保留灌肠对重症有机磷中毒患者血清瓜氨酸水平及胃肠功能的影响

目的探讨大黄鼻饲、保留灌肠对重症有机磷中毒患者血清瓜氨酸水平及胃肠功能的影响。方法68例患者按入院先后顺序编码、按随机数字表法随机分为对照组和观察组两组各34例。对照组给予解毒剂阿托品、复能剂氯解磷定、血液灌流等综合治疗。观察组在对照组基础上给予生大黄鼻饲及保留灌肠。两组均连续治疗3 d。比较两组胃肠道功能恢复正常的时间和胆碱酯酶、血清瓜氨酸的变化情况,以及两组患者住重症监护室的时间。结果68例患者均全部治愈出院,无死亡病例。观察组胃肠障碍恢复至正常所需时间和住ICU时间均短于对照组(P<0.05)。在给予大黄鼻饲、保留灌肠治疗前,两组全血胆碱酯酶活力及血清瓜氨酸含量比较,差异无统计学意义(均P>0.05)。给予大黄鼻饲、保留灌肠治疗第3日,两组各指标均明显升高,观察组全血胆碱酯酶活力及血清瓜氨酸含量均高于对照组(均P<0.05)。结论生大黄鼻饲及灌肠可改善重症有机磷中毒患者胃肠功能,提高患者血清瓜氨酸水平,缩短病程,提高临床疗效。     

Nutritional therapy complications in children with ultra‐short bowel syndrome include growth deficiency but not cholestasis

Aim

Children with ultra‐short bowel syndrome (USBS) have not been extensively studied to date because the condition is rare. The aim of the study was to assess the nutritional status of children with USBS receiving home parenteral nutrition, using citrulline serum concentration and cholestasis.

Methods

We studied 17 patients with USBS, with a median age of 6.6 years and median duration of parenteral nutrition of 6.6 years. The study was carried out at The Children's Memorial Health Institute, Warsaw, from January 2014 to January 2015.

Results

The median standard deviation score (SDS) was ?1.2 for body mass according to chronological age, ?1.72 according to height and ?0.59 according to height for age. Patients requiring seven days per week parenteral nutrition had a citrulline concentration below 10 μmol/L. Decreased bone‐mineral density was observed in 87% of the patients. Low values of 25‐hydroxyvitamin D were found in 53% of the children. None of the patients had elevated conjugated bilirubin levels above 34.2 μmol/L.

Conclusion

Children with USBS were growth deficient according to their chronological age, with frequent abnormal bone mineralisation and vitamin D deficiency. Children requiring parenteral nutrition seven days a week had citrulline concentrations below 10 μmol/L. Cholestasis was not seen.

     

Prediction,identification and progression of histopathological liver disease activity in children with intestinal failure

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严重多发伤患者血清瓜氨酸水平与肠功能损伤的相关性

目的探究血清瓜氨酸水平在评估多发伤患者急性肠功能损伤中的临床意义。 方法采用前瞻性研究方法,纳入上海市第一人民医院急诊危重病科自2017年6月至2018年2月收治的40例多发伤患者。根据创伤严重度评分（ISS）分为轻度创伤组（ISS<16分,21例）、重度创伤组（ISS≥16分,19例）。再根据急性胃肠损伤（AGI）分级将患者分为4个亚组,即AGI 0组12例、AGI Ⅰ组9例、AGI Ⅱ组14例、AGI Ⅲ组5例。同时设对照组（健康志愿者,10例）,分别于创伤后第1、3、6天采集外周血,应用高效液相色谱法测量血清瓜氨酸水平,应用肠道屏障功能生化指标分析系统测量血二胺氧化酶,D-乳酸,细菌内毒素水平。 结果重度创伤组、轻度创伤组第1、3、6天血清血清瓜氨酸水平较对照组明显降低（P<0.05）,且第1天重度创伤组低于轻度创伤组（P<0.05）,第3天轻度创伤组血清瓜氨酸水平较第1天进一步下降,而伤后第6天轻度创伤组、重度创伤组血清瓜氨酸水平仍都低于对照组。不同AGI亚组血清瓜氨酸水平随着分级越高,其水平下降越显著（P<0.05）。第3天AGI 0、AGIⅡ亚组血清瓜氨酸水平较第1天均进一步下降（P<0.05）。血清瓜氨酸水平与ICU住院时间、ISS评分、AGI分级、血浆二胺氧化酶、D-乳酸毒素水平呈负相关。血清瓜氨酸水平与有创呼吸机时间、细菌内毒素水平未见明显相关性。血清瓜氨酸≤19.56 μmol/L可能是预测严重创伤后AGI较好的界值。 结论严重多发伤患者血清瓜氨酸水平对评估创伤后早期肠功能损伤可能具有一定临床价值。     

血浆瓜氨酸在胃肠损伤中的研究进展

急性胃肠损伤是指危重症患者由于急性疾病引起的胃肠功能障碍。危重症患者常常发生急性胃肠损伤,且常为多脏器功能不全或多脏器功能衰竭的关键因素,可加重其他器官的损伤,加速疾病的进展。由于缺乏特异度生物指标,给该病的早期干预带来障碍。瓜氨酸为非蛋白质氨基酸,主要由谷氨酰胺作为前体物质在肠黏膜中特异性合成,其反映肠道功能的可靠性已在短肠综合征、肠移植排斥反应、放疗化疗后肠损伤、肠绒毛破坏性疾病等胃肠功能障碍的研究中得到证实。因此,近年来瓜氨酸也被作为监测危重症患者急性胃肠损伤的早期标志得到广泛研究。