Apoptosis and surgical trauma -: Dysregulated expression of death and survival factors on peripheral lymphocytes

Apoptosis and surgical trauma -: Dysregulated expression of death and survival factors on peripheral lymphocytes
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DOI:
10.1001/archsurg.135.10.1141
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发表时间:
2000-10-01
影响因子:
--
通讯作者:
De Simone, C
De Simone, C
中科院分区:
其他
文献类型:
--
作者:
Delogu, G;Moretti, S;De Simone, C

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背景资料:手术和麻醉会导致术后细胞介导的免疫功能下降,包括循环淋巴细胞数量的减少。有人声称,这种免疫抑制是与术后infecties.Hypothesis发病率增加:淋巴细胞减少症手术创伤后依赖于一个失调的表达死亡/和与凋亡相关的生存因素,反过来,干扰术后infecties.Design的发生:15例接受择期手术全身麻醉下进入研究。将术后结果期间发生感染的患者的数据与未发生感染的患者的数据进行比较。主要观察指标:分别于术前、术后24 h、96 h抽取外周血,观察两组患者的生存情况。分离淋巴细胞,并使用7-氨基-放线菌素D方法进行细胞凋亡的定量和表型分析,以及Fas和Pas配体,白细胞介素1转换酶p20/caspase-1,Bcl-2和p35表达。细胞凋亡率与术后感染发生率相关。地点:大学医院。结果:术后24小时,CD 4(+)和CD 8(+)细胞凋亡率以及Fas和Fas配体酸性白细胞介素1转化酶p20/caspase-1的表达明显高于术前。这种增加被抗凋亡因子如Bcl-2的显著下调所抵消。然而,促凋亡因子p35的表达减少。此外,我们发现凋亡CD 8(+)亚群的比率与术后感染并发症的发生之间存在关系。在手术后96小时,研究的变量返回到基线levels.Conclusions:在术后早期,全身麻醉下的手术创伤诱导外周淋巴细胞的细胞内扰动,导致死亡信号因子的上调和生存信号因子的下调。CD 8(+)淋巴细胞凋亡增加,而不是CD 4(+)细胞,似乎与术后感染的风险更大。
Background: Surgery and anesthesia cause depression of cell-mediated immunity in the postoperative period, including a reduction in the numbers of circulating lymphocytes. It has been claimed that this immunosuppression is associated with an increased incidence of postoperative infections.Hypothesis: Lymphocytopenia following surgical trauma depends on a dysregulated expression of death/and survival factors associated with apoptosis that, in turn, interferes with the occurrence of postsurgical infections.Design: Fifteen subjects undergoing elective surgery under general anesthesia entered the study. The data of the patients who had infections during the postoperative outcome were compared with the data of those who did not. The data were collected prospectively.Main Outcome Measures: Peripheral blood samples were drawn before the operation, and 24 hours and 96 hours after the operation. Lymphocytes were isolated and examined for quantification and phenotypic analysis of apoptosis using the 7-amino-actinomycin D method, as well as for Fas and Pas ligand, interleukin 1-converting enzyme p20/caspase-1, Bcl-2, and p35 expression. The rate of apoptotic cells was correlated with the incidence of postoperative infections.Setting: University hospital.Results: Twenty-four hours after surgery, CD4(+) and CD8(+) cells exhibited a significantly higher frequency of apoptosis as well as of Fas and Fas ligand acid interleukin 1-converting enzyme p20/caspase-1 expressions than preoperatively. This increase was paralleled by a significant down-regulation of antiapoptotic factors such as Bcl-2. However, the expression of the proapoptotic factor p35 was reduced. In addition, we found a relationship between the rate of the apoptotic CD8(+) subset and the occurrence of infectious complications during the postoperative course. At 96 hours after surgery, the variables studied returned to the baseline levels.Conclusions: In the early postoperative period, surgical trauma under general anesthesia induces an intracellular perturbation on peripheral lymphocytes, resulting in both up-regulation of death-signaling factors and down-regulation of survival-signaling factors. The increased apoptosis of CD8(+) lymphocytes, but not of CD4(+) cells, seemed to be associated with a greater risk of postsurgical infections.