脓毒症时硫化氢对大鼠下丘脑-垂体-肾上腺轴应答的影响  

Effects of hydrogen sulfide on rats hypothalamic-pituitary-adrenal axis response during sepsis

作　　者：彭超[1] 乔玮[1] 庞众多[2] 岳建云 祁英文 鲁彦[2] 柴琛[1] 

机构地区：[1]兰州大学第一医院普外科,甘肃兰州730000 [2]解放军第一医院检验科,甘肃兰州730000

出　　处：《中国急救医学》2016年第11期975-979,共5页Chinese Journal of Critical Care Medicine

基　　金：甘肃省自然科学基金项目（1308RJZA269）

摘　　要：目的：探讨脓毒症时硫化氢（H2S）对血清皮质酮（CORT）、促肾上腺皮质激素（ACTH）和下丘脑促肾上腺皮质激素释放激素（CRH）浓度的影响。方法以盲肠结扎穿刺法（CLP）制作脓毒症大鼠模型，63只大鼠随机分为9组。假手术组；CLP 6 h、12 h、24 h组；CLP 12 h＋生理盐水（NS）组；CLP 12 h ＋硫氢化钠（NaHS）组；CLP 12 h ＋羟氨（HA）＋炔丙基甘氨酸（PAG）组；CLP 12 h ＋HA组；CLP 12 h ＋PAG组（每组7只）。单纯CLP大鼠在术后6 h、12 h、24 h处死，CLP＋给药组大鼠术前1 h给予不同药物后于CLP术后12 h处死。收集血清及下丘脑组织标本；采用酶联免疫吸附试验（ELISA）法检测血清 CORT、ACTH 和下丘脑 CRH 浓度。结果①CLP 术后6 h、12 h、24 h 血清 CORT、ACTH 和下丘脑 CRH 浓度均显著升高（P 值均＜0.05），术后12 h、24 h 血清CORT、ACTH和下丘脑CRH浓度均显著高于术后6 h（P值均＜0.05），术后24 h血清CORT浓度显著低于术后12 h（P＜0.05），术后24 h 血清 ACTH 浓度显著高于术后12 h（P＜0.05）。②脓毒症时腹腔注射NaHS显著降低血清CORT、ACTH浓度和下丘脑CRH浓度（P值均＜0.05）。③脓毒症时同时抑制中枢/外周内源性 H2S 生成，显著升高血清 CORT、ACTH 和下丘脑 CRH 浓度（P 值均＜0.05）。单独抑制外周 H2S 生成升高血清 CORT 浓度（P＜0.05），降低下丘脑 CRH 浓度（P＜0.05），但不影响血清 ACTH 浓度（P＞0.05）。结论脓毒症时 HPA 轴激活，H2S 通过中枢和外周机制抑制HPA轴应答。Objective To investigate the effects of hydrogen sulfide（H2S）on serum corticoste-rone（CORT）, adrenocorticotropin（ACTH）and hypothalamic corticosterone（CRH）concentration in septic rats. Methods Sepsis was induced in adult male Sprague-Dawley（SD）rats by cecal ligation and puncture（CLP）. Sixty-three rats were randomly divided into nine groups： sham operation group;sepsis 6 h, 12 h, 24 h groups; CLP 12 h ＋ sodium hydrosulfide（NaHS）; CLP 12 h ＋ hydroxylamine （HA）＋ propargylglycine（PAG）group; CLP 12 h＋ HA group; CLP 12 h＋ PAG group（n=7 in every group）. CLP only rats were sacrificed at 6 h, 12 h, 24 h after CLP. The others received intraperitoneal in-jection of different drugs 1 h before CLP and were sacrificed at 12 h after CLP. The samples of serum or hypothalamus were collected. Serum CORT, ACTH and hypothalamic CRH concentration were detected by enzyme-linked immunosorbent assay（ELISA）. Results ①Serum CORT, ACTH and hypothalamic CRH concentrations increased significantly 6 h, 12 h, 24 h after CLP（all P〈0.05）. Serum CORT, ACTH and hypothalamic CRH concentrations were significantly higher 12 h, 24 h after CLP than that of 6 h after CLP（all P〈0.05）. Serum CORT concentration at 24 h after CLP was significantly higher than that 12 h after CLP（P〈0.05）, serum ACTH concentration was significantly lower than that 24 h after CLP（P〈0.05）. ②Inhibition of central or peripheral H2S generation increased serum CORT, ACTH and hypothalamic CRH concentrations（all P〈0.05）. Inhibition of the production of central H2S increased serum CORT, ACTH and hypothalamic CRH concentration（all P〈0.05）. Inhibition of the production of peripheral H2S increased serum CORT concentration（P〈0.05）and decreased hypothalamic CRH concentration（P〈0.05）. Serum ACTH concentration did not significantly changed（P〈0.05）. Con-clusion HPA axis is active during sepsis; H2S inhibit HPA axis response by central and peripheral mechanism during sepsis.

关 键 词：脓毒症 下丘脑-垂体-肾上腺轴(HPA轴) 硫化氢(H2S) 

分 类 号：R285.5[医药卫生—中药学]