兔出血性休克并腹内压升高后中性粒细胞免疫机能抑制

Suppression of neutrophil immune function in rabbit models of hemorrhagic shock complicated by intra-abdominal hypertension

目的探讨腹内压升高对外周血中性粒细胞炎性反应能力的影响。方法将24只家兔随机均分为A(出血性休克并发腹内压升高)、B(出血性休克)、C(腹内压升高)、D(对照)4组。分别于创伤前、创伤后及创伤后4 h,采用流式细胞仪检查中性粒细胞内细胞因子的产生、化学发光法检查中性粒细胞的吞噬能力、免疫细胞化学检测NF-κB的表达。结果创伤后4 h,A组较创伤前及其余各组中性粒细胞内细胞因子产生减少、吞噬能力下降,NF-κB表达抑制(P<0.05);B和C组除在创伤早期有所变化外,创伤后4 h恢复到创伤前水平;D组各时间点无显著变化。结论出血性休克后腹内压升高对机体形成序贯性二次打击,导致中性粒细胞对内毒素的刺激反应性下降,免疫机能抑制。这可能有助于解释腹部间区综合征中发生败血症的病理生理学机制。

Objective To investigate the effects of hemorrhagic shock and intra-abdominal hypertension (IAH) on inflammatory responses of peripheral circulating neutrophils such as intracellular cytokine production, phagocytic capacity and expression of nuclear factor (NF)-κB. Methods Twenty-four rabbits were divided equally into 4 groups including a hemorrhagic shock (HS) group complicated by abdominal compartment syndrome (ACS) (Group A) , a HS group (Group B), a ACS group (Group C) and a normal control group (Group D). Intracellular interleukin (IL)-8 production in the peripheral neutrophils were measured in the rabbits by flow cytometry, phagocytic function of the neutrophils evaluated by a chemiluminescence method and the NF-κB expression detected by immunocytochemistry before, immediately and 4 h after the traumatization. Results Four hours after the trauma, decreased intracellular IL-8 production and impaired phagocytic function of the peripheral neutrophils were observed in Group A along with suppressed NF-κB expression. But in Group B and Group C, the intracellular IL-8 production, phagocytic function and expression of NF-κB returned to the normal levels 4 hours after the trauma following the early-stage changes. In Group D, no significant changes occurred during the observation. Conclusions Responsiveness and function of the neutrophils to the stimuli by endotoxin are suppressed by the sequential second-hit of IAH after hemorrhagic shock, which may contribute to the occurrence of sepsis in ACS.