脓毒症患者肾上腺皮质功能不全的新认识

Progress in understanding of adrenal insufficiency in septic patients

背景 脓毒症是严重创伤、大手术后的重要并发症,是导致患者死亡的重要原因,其中脓毒性休克的病死率超过40％.目前已发现脓毒症患者的肾上腺皮质功能状态直接影响病情严重程度和预后,使用糖皮质激素（glucocorticoid,GC）具有一定效果,但是存在一定争议,而且肾上腺皮质功能不全的发生机制不清. 目的 为及时评估患者肾上腺皮质功能状态,适时、适量给予外源性GC,较精准地代偿受损的肾上腺皮质功能提供依据,以改善预后和降低病死率. 内容 脓毒症早期下丘脑-垂体-肾上腺轴（hypothalamus-pituitary-adrenal axis,H-P-A轴）被激活,GC分泌增加.GC主要通过抑制丝裂原蛋白激酶（mitogen activated protein kinase,MAPK）和核因子-κB（nuclear factor-κB,NF-κB）等途径抑制炎症级联反应.在脓毒症晚期和脓毒性休克患者,肾上腺皮质细胞和血管内皮细胞受损造成皮质功能不全,表现为GC分泌不足及其受体亲和力减低.血皮质醇水平和促肾上腺皮质激素（adrenocorticotrophic hormone,ACTH）水平用以评估肾上腺皮质功能,也辅助诊断肾上腺功能不全（adrenal insufficiency,AI）和相对肾上腺功能不全（relative adrenal insufficiency,RAI）.小剂量GC可提高脓毒性休克的逆转,代偿肾上腺皮质功能,有利于维持脓毒症患者的循环稳定. 趋向 需要更深入地研究脓毒症合并AI和RAI的发生机制以进一步完善脓毒症的GC治疗.

Background Sepsis is one of the critical complications following serious injuries or major surgeries.It is a leading cause of death.The mortality of septic shock exceeds 40%.Accumulating studies have demonstrated that the severity of adrenal cortex dysfunction has a vital impact on the phenotype and prognosis of sepsis,while glucocorticoid （GC） may be an effective intervention.However,the mechanisms underlying adrenocortical dysfunction remain unclear.Objective To review strategies for assessment of adrenocortical function,and timely supplement of GC,aiming to appropriately compensate the impaired adrenal function,finally,to improve prognosis and to reduce mortality of sepsis.Content At the early stage of sepsis,hypothalamuspituitary-adrenal axis （H-P-A） is activated,and is followed by release of GC and mobilization of inflammation cascades,especially mitogen-activated protein kinase（MAPK） and nuclear regulatory factor-κB pathways.GC counteracts the inflammation cascades.At the late stage of sepsis or during sepsis shock,damages of adrenocortical cells and vascular epithelia cells occur in adrenal gland,resulting in adrenocortical dysfunction,including low levels of GC and low affinity of GC receptors.The measurement of serum GC and adrenocorticotrophic hormone are combined to assess adrenocortical function：adrenal insufficiency （AI） or relative adrenal insufficiency （RAI）.Low doses of GC help to reverse septic shock,improve adrenal function,and maintain normal hemodynamics in septic patients.Trend Further investigation in understanding the mechanisms underlying AI and RAI are highly demanded to optimize therapeutic application of GC in sepsis.