脓毒症中同型半胱氨酸转硫代谢障碍的机制研究  

Mechanism study of impaired homocysteine transsulfuration metabolism in sepsis

作　　者：黄贺 吴箬凡 施正康 洪怡 范紫薇 樊丹 陆洁 吴水燕 侯晓鸥 胡丽芳[5] 柏振江[3] Huang He;Wu Ruofan;Shi Zhengkang;Hong Yi;Fan Ziwei;Fan Dan;Lu Jie;Wu Shuiyan;Hou Xiaoou;Hu Lifang;Bai Zhenjiang(Emergency Department,Xuzhou Children′s Hospital,Xuzhou Medical University,Xuzhou 221000,China;Medical Department,Xuzhou Children′s Hospital,Xuzhou Medical University,Xuzhou 221000,China;Department of Pediatric Intensive Care Unit,Children′s Hospital of Soochow University,Suzhou 215000,China;Department of Pediatrics,Changshu Hospital Affiliated to Nanjing University of Chinese Medicine,Changshu 215500,China;Institute of Neuroscience,Soochow University,Suzhou 215000,China)

机构地区：[1]徐州医科大学附属徐州儿童医院急诊科,221000 [2]徐州医科大学附属徐州儿童医院医务科,221000 [3]苏州大学附属儿童医院重症医学科,215000 [4]南京中医药大学附属常熟市中医院儿科,215500 [5]苏州大学神经科学研究所,215000

出　　处：《中国小儿急救医学》2023年第12期930-936,共7页Chinese Pediatric Emergency Medicine

基　　金：江苏省自然科学基金项目(BK20210097、BK20211077);姑苏卫生人才培养项目(GSWS2019015、GSWS2020044);徐州市儿童医院2022年度科研项目(22040416);2022年度常熟市卫生健康委员会科技计划(CSWS202223)。

摘　　要：目的探讨脓毒症患儿外周血同型半胱氨酸(Hcy)水平升高的临床意义及其可能机制。方法回顾性分析2019年1月至2019年12月徐州市儿童医院PICU收治的51例脓毒症患儿(脓毒症组)的临床资料,并与同期住院的50例感染非脓毒症患儿(普通感染组)及50例健康体检儿童(健康对照组)的血浆Hcy水平进行比较;通过脂多糖诱导脓毒症小鼠模型检测Hcy代谢下游关键限速酶胱硫醚-β合酶(CBS)和胱硫醚-γ裂合酶(CSE)的水平,分析Hcy代谢障碍的可能机制。结果脓毒症组患儿血浆Hcy水平为(12.62±5.46)μmol/L,显著高于普通感染组[(9.42±2.28)μmol/L]和健康对照组[(8.14±1.60)μmol/L],差异均有统计学意义(P<0.05);脓毒症组中12例发生急性肾损伤患儿血浆Hcy水平为(16.48±5.87)μmol/L,显著高于39例未发生急性肾损伤患儿[(11.62±4.74)μmol/L],差异有统计学意义(P<0.05);脓毒症组中6例发生急性肝衰竭患儿血浆Hcy水平为(18.35±7.10)μmol/L,显著高于45例未发生急性肝衰竭患儿[(11.84±4.78)μmol/L],差异有统计学意义(P<0.05)。脓毒症小鼠血清Hcy水平显著升高(P<0.01);脓毒症小鼠肝脏及肾脏组织中Hcy代谢的关键限速酶CBS和CSE的转录及蛋白表达水平均显著下调(P<0.05)。结论脓毒症患儿的外周血Hcy水平升高,在发生急性肾损伤和急性肝衰竭患儿中升高更加明显;脓毒症时可能通过抑制Hcy转硫代谢的关键酶CBS及CSE表达导致Hcy转硫代谢发生障碍,从而引起血Hcy水平升高。Objective To investigate the clinical significance and possible mechanisms of elevated homocysteine(Hcy)levels in peripheral blood of children with sepsis.Methods The clinical data of 51 children with sepsis(sepsis group)admitted to PICU at Xuzhou Children′s Hospital from January 2019 to December 2019 were analyzed,and the levels of Hcy in plasma were compared with 50 non-septic children(common infection group)and 50 healthy children(healthy control group)during the same period.The possible mechanism of metabolic disorders about Hcy was analyzed by detecting the levels of the key rate-limiting enzymes cystathionine-β-synthase(CBS)and cystathionine-γ-lyase(CSE),which were in the downstream of metabolism in septic mouse model induced by lipopolysaccharide.Results The level of Hcy in plasma was(12.62±5.46)μmol/L in sepsis group,which was significantly higher than those in common infection group[(9.42±2.28)μmol/L]and healthy control group[(8.14±1.60)μmol/L](P<0.05).The level of Hcy in plasma of 12 children with acute kidney injury in sepsis group was significantly higher than that of 39 children without acute kidney injury in sepsis group[(16.48±5.87)μmol/L vs.(11.62±4.74)μmol/L,P<0.05].The level of Hcy in plasma of six children with acute liver failure in sepsis group was significant higher than that of 45 children without acute liver failure in sepsis group[(18.35±7.10)μmol/L vs.(11.84±4.78)μmol/L,P<0.05].The level of Hcy in serum significantly increased in septic mouse models(P<0.01).The transcription and protein expression levels of key rate-limiting Hcy transcription enzymes CBS and CSE in liver and kidney tissues of septic mouse were significantly down-regulated(P<0.05).Conclusion The level of Hcy in peripheral blood of children with sepsis increases,which is more obviously in children with acute kidney injury or acute liver injury.When patients developed sepsis,the expression of CBS and CSE will be restrained,leading to disorders related to transsulfuration metabolism and elevated level of Hc

关 键 词：脓毒症 同型半胱氨酸 胱硫醚-β合酶 胱硫醚-γ裂合酶 急性肾损伤 急性肝衰竭 

分 类 号：R720.597[医药卫生—急诊医学]