巯基化合物对内毒素诱导大鼠枯否细胞NF—kB活性和肿瘤坏死因子释放的影响

目的 观察巯基化合物对内毒素诱导大鼠枯否细胞（KC）NF-kB活性和肿瘤坏死因子-a（TNF-a）释放的影响。方法采用胶原酶灌注和percoll密度梯度离心法分离得到高纯度大鼠KC，在过夜培养后冲洗两遍（不含血清），加入内毒素（LPS）10ng／ml刺激原代培养的KC，观察不同浓度谷胱甘肽乙基酯（GSHEE）及N-乙酰半胱氨酸（NAC）对大鼠KCTNF-a释放和KC内谷胱甘肽（GSH）及NF-kB活性的影响。并观察使用谷胱甘肽合成抑制剂BSO后，对NAC抑制炎症因子的影响，采用凝胶滞留电泳法测NF-kB活性，采用高效液相色谱分析法测GSH水平。结果 LPS诱导KC中GSH水平无变化；GSHEE和NAC可提高KC中GSH水平（P〈0．05），降低NF-kB活性和TNF-a释放（P〈0．05）。NAC与BSO合用时KC中GSH水平无变化，TNF-a释放降低（P〈0．05）。结论 NAC通过抑制KC中NF-kB的激活和TNF-a的释放调节KC功能，但这种抑制作用并非通过增加GSH介导。     

内毒素导致白细胞急剧升、降10倍一例报导

目的探索白细胞(WBC)数小时内急剧升、降原因。方法收集患者入院时首次血、尿细菌培养结果;取患者1周内7次EDTA-K2抗凝血标本,在STKS全自动血细胞分析仪上,与高、中、低定值全血质控品同时进行比对测定,每个样本平行分析4次求均值,同时检测患者6次血清标本内毒素含量,统计数据。结果测得仪器批内误差CV0.18%;其中14小时内5个样本WBC均数(x)分别为20.1×109/L、2.3×109/L、3.2×109/L、22.8×109/L、15.7×109/L;血、尿均分离到大肠埃希氏菌,内毒素试验阳性。结论内毒素导致WBC贴壁,造成病危期4小时内周围血液WBC急剧下降10倍;临床在分析实验结果时既要考虑内毒素导致WBC上升,又要考虑内毒素致使WBC贴壁造成急剧下降现象。     

地塞米松对内毒素休克新生大鼠脑一氧化氮合成酶基因表达的调节

目的：探讨新生大鼠内毒素休克脑损伤时脑一氧化氮合成酶(NO6)三种亚型基因表达的变化及地塞米松(DEX)对其的调控作用。方法：在新生大鼠内毒素休克动物模型基础上，采用逆转录PCR及PCR技术，对脑组织中三型NOS mRNA及caspase—3 mRNA的表达进行半定量分析。结果：正常新生大鼠脑iNOS及eNOS mRNA无明显表达，nNOS mRNA、caspase—3 mRNA有一定程度表达。内毒素脂多糖(LPS)腹腔注射后2h，三种亚型NOS mRNA开始表达，于LPS6h达高峰，并持续至24h。caspase—3 mRNA于LPS腹腔注射后2h后表达逐渐增加，24h达高峰。DEX可抑制nNOS、iNOS及caspase—3 mRNA的表达，且以用药后2h最为明显，并持续至用药后24h。结论：内毒素休克脑损伤时，各型NOS均有表达，NO的产生是内毒素休克脑损伤时重要的病理生理机制之一。DEX通过抑制NOS、caspase—3 mRNA的表达部分实现其神经保护作用．     

Management of abdominal sepsis

Introduction: Today the management of the different forms of peritonitis is generally standardised. The classification of primary and secondary peritonitis is well accepted. From a pathophysiological point of view, postoperative and post-traumatic peritonitis should be considered as independent entities. The bacteriological isolates from the inflamed peritoneal cavity do not correlate with the clinical course, and the occurrence of enterococci and bacteroides may be slightly related to ongoing infectious complications. Classification: Valuable scoring systems mainly rely on systemic signs of the septic disease and seem to better differentiate the prognosis of the disease than more surgically oriented scores do. Although the scoring systems did not allow any clinical decision, they should be used to help better compare patients treated in different institutions. The observation of the minor relevance of bacteriology and the superiority of general sepsis scores agrees with the fact that pre-existing septic organ dysfunction and pre-existing comorbidity are the main determinants of mortality. Treatment: Surgical therapy focuses on the control of the source of infection because it has been clearly shown that, without resolving the source of infection, the prognosis remains poor. Adjuvant surgical measures aim at the further reduction of the bacterial load in the peritoneal cavity. Planned relaparotomy, relaparotomy on demand, and continuous closed peritoneal lavage are used. Results: Clinical results proved these methods to be equally effective although pathophysiological considerations favour closed peritoneal lavage. Conclusion: Summarising the available data, we need a more sophisticated understanding of the pathophysiology of the peritonitis, and well-designed clinical studies are necessary to define the optimal surgical treatment modalities. Received: 27 November 1997     

Response of body temperature and serum iron concentration to repeated pyrogen injection in rabbits

We measured body temperature and serum iron concentration after five daily consecutive injections of febrile doses of Salmonella typhosa lipopolysaccharide (0.1 g/kg) and two doses of Staphylococcus aureus cell walls (1×10⁷ and 5×10⁷ cells) in rabbits. Tolerance to endotoxin injection, as manifest by a significant attenuation in the body temperature elevation, developed after the first injection of endotoxin. The endotoxin-induced fall in serum iron concentration was attenuated significantly by the 5th day of endotoxin injection. In contrast, no tolerance developed in either the body temperature or serum iron response following repeated daily injections of S. aureus. Rabbits rendered tolerant to endotoxin showed normal febrile and serum iron responses to subsequent S. aureus injection. Rabbits given serial injections of S. aureus, although not tolerant to S. aureus itself, exhibited attenuated body temperature responses but not serum iron responses to endotoxin injection. We suggest that repeated injection of endotoxin diminishes the ability of endotoxin to stimulate endogenous pyrogen (EP) synthesis and/or release, a property not shared by the gram-positive pyrogen S. aureus. However, repeated injection of S. aureus weakens the central endotoxin-EP pathway.     

Regulation of cytokine synthesis in cardiac surgery: Role of extracorporeal circuit and humoral mediators <Emphasis Type="Italic">in vivo</Emphasis> and <Emphasis Type="Italic">in vitro</Emphasis>

Objective and design: Cardiopulmonary bypass (CPB) impairs monocyte and neutrophil proliferation, cytokine synthesis, and antigen presentation. This study compares in vivo data with results from an extracorporeal circulation (ECC) model, distinguishing direct effects on cytokine synthesis from regulatory mechanisms. Patients and methods: Whole blood from 18 patients prior to, during and after CPB was stimulated with lipopolysaccharide (LPS). Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 levels were measured. Additionally, blood from 4 volunteers was circulated in an ECC model. Cytokine levels were measured before and during mock ECC. Results: LPS-induced cytokine synthesis was reduced after CPB (TNF-α: 11 %; IL-6: 29 %; IL-8: 48 % of preoperative values, all p < 0.001). In mock ECC, cytokine production (except IL-8) was suppressed: TNF-α production was lowest 60 min after starting ECC, IL-6 synthesis was lowest at 90 min (33 % and 15 % vs. pre-ECC levels; both p < 0.001). Patient sera contained cytokine-inhibitory activity after CPB, an activity not found in mock ECC. Conclusions: (1) In patients, CPB induces early transient LPS hyporesponsiveness; (2) blood contact with foreign surfaces induces LPS hyporesponsiveness; (3) serum cytokineinhibitory activities are released after CPB, but not in mock ECC. Impaired leukocyte function may explain increased susceptibility to infections after CPB. Received 16 September 2006; accepted without revision by K. Visvanathan 18 October 2006     

精氨酸加压素对家兔血细胞生成内生致热原的影响

本文观察了精氨酸加压素对体外培育的兔全血细胞产生内生致热原的影响。结果表明，ＡＶＲ对内毒素诱生ＥＰ过程有明显抑制作用；而ＡＶＰ单独与血细胞培养无降温物质产生；同时，所用剂量的ＡＶＰ对ＥＰ性发热无直接抑制作用。因此作者认为，ＡＶＰ１能够抑制ＥＴ诱生家兔血细胞生成ＥＰ，这可能是其降低或阻断ＥＴ性发热的主要机制之一。     

电针退热时家兔的血浆及脑脊液中前列腺素E_2含量的变化

本实验用家兔复制内毒素性发热模型,观察电针退热时血浆,CSF中PGE_2含量的变化。实验结果表明:在发热高峰期,两组动物的血浆、CSF中PGE_2含量都比发热前明显升高(P<0.091)。电针对内毒素性发热有明显地抑制作用。电针组动物的血浆及CSF中PGE_2含量明显低于对照组(P<0.001)。作者推论:PGE_2是内毒素性发热的一种中枢性发热介质,电针的退热作用可能是通过一种未知方式抑制中枢PGE_2的产生或释放而实现的。     

脂多糖诱导的小鼠腹腔巨噬细胞基因表达谱分析

目的　利用基因芯片技术分析脂多糖 (LPS)活化的小鼠腹腔巨噬细胞基因表达谱 ,以更全面地了解LPS诱导的巨噬细胞反应。方法　以未刺激的和用 1mg/LLPS刺激的小鼠腹腔巨噬细胞制备3 3 P标记的cDNA探针 ,分别与含有 1176个已知基因的小鼠cDNA芯片杂交。结果　活化组和未刺激组间的 2倍差异表达基因为 118个 ,3倍差异表达基因为 6 9个 ,其中 4 4个上调 ,2 5个下调。转录因子、细胞内信号调节蛋白、炎症细胞因子和细胞凋亡相关基因的转录发生明显的调节变化。结论提供了LPS活化的巨噬细胞综合基因表达信息 ,并筛选出一些新的可能与LPS活化相关的基因。