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[目的]探讨多器官功能障碍综合征(MODS)时体内中性粒细胞(PMN)凋亡延迟的潜在原因,以增加对全身炎症反应内源性保护机制的认识。[方法]将15只猕猴分为正常对照组、肠缺血再灌注(IIR)组、IIR+生长抑素(SST)组,每组5只。用放射免疫分析法测定各组外周血、肠黏膜SST浓度,SST与猕猴外周血PMN共同孵育后,观察猕猴外周血PMN的形态变化,流式细胞仪测定细胞凋亡率,电泳分析PMN细胞DNA断裂片段,生物分子相互作用系统检测PMN上SST受体(SSTR-1,SSTR-2)。[结果]IIR后,猕猴外周血及小肠黏膜中SST含量均明显下降;IIR组IIR 24h后PMN凋亡率降至(3.5±0.5)%,与IIR+SST组[(7.5±1.4)%]、正常对照组[(15.4±1.4)%]比较均差异有统计学意义(P<0.05);腹腔巨噬细胞凋亡率则明显增加,与IIR+SST组、正常对照组比较[(20.2±1.8)%∶(17.5±1.2)%、(14.1±1.6)%]均差异有统计学意义(P<0.05);SSTR在IR时表达下降,静脉滴注SST后随着全身状况的好转,SSTR表达增加。[结论]生理状态下,SST通过猕猴外周血PMN上SSTR介导,诱导其凋亡;IIR后猕猴外周血及小肠黏膜中SST含量明显下降,这使得PMN寿命延长,从而推动了全身炎症反应综合征和MODS的发生。
[Objective] To explore the underlying causes of delayed neutrophil (PMN) apoptosis in patients with multiple organ dysfunction syndrome (MODS) and to increase the understanding of the endogenous protective mechanisms of systemic inflammatory response. [Methods] Fifteen cynomolgus monkeys were divided into normal control group, intestinal ischemia reperfusion (IIR) group and IIR + somatostatin (SST) group. The concentrations of SST in peripheral blood and intestinal mucosa of each group were measured by radioimmunoassay. The morphological changes of peripheral blood mononuclear cells (PMN) were observed after incubated with SST and PMN in peripheral blood mononuclear cells. The apoptosis rate was determined by flow cytometry. SST receptor (SSTR-1, SSTR-2) on the PMN was detected by the fragment and biomolecular interaction system. [Results] After treatment with IIR, the content of SST in peripheral blood and intestinal mucosa decreased significantly. The apoptosis rate of PMN in IIR group decreased to (3.5 ± 0.5)% after IIR compared with [(7.5 ± 1.4)%] in IIR + SST group (P <0.05). The apoptosis rate of peritoneal macrophages was significantly increased compared with that of the control group [(15.4 ± 1.4)%], compared with that in the IIR + SST group and the normal control group [(20.2 ± (17.5 ± 1.2)%, (14.1 ± 1.6)%] (P <0.05). The expression of SSTR decreased at IR. After systemic infusion of SST, SSTR Increased expression. [Conclusion] Under physiological conditions, SST mediates and induces apoptosis through the SSTR on PMN in peripheral blood of macaques. The content of SST in peripheral blood and intestinal mucosa of macaques significantly decreased after IIR, which prolongs the life span of PMN and promotes the synthesis of systemic inflammatory response Signs and the occurrence of MODS.