促炎症和抗炎症细胞因子基因表达与脓毒症小鼠肝损伤的关系

目的 探索促炎症及抗炎症细胞因子在脓毒症小鼠肝损伤中的作用。方法 盲肠结扎穿孔（ＣＬＰ）造成小鼠脓毒症模型,假手术（sham）组接受同样手术操作且不行ＣＬＰ。用ＲＴ－ＰＣＲ的方法检测了脓毒症小鼠肝组织中多种细胞因子（促炎症细胞因子ＴＮＦα、ＩＬ－１β、ＩＬ－６,抗炎症细胞因子ＩＬ－４）mＲＮＡ的表达,同时还测定了肝组织含水量及微血管通透性的改变。结果 与sham组相比,ＣＬＰ小鼠在３h后ＴＮＦα、ＩＬ－１β基因表达即明显增高（Ｐ＜０.０１）,至１２h仍然高于sham组（Ｐ＜０.０１）,但较３h有所降低;ＩＬ－６基因在ＣＬＰ后３h也明显增高（Ｐ＜０.０１）,并且在ＣＬＰ后１２h仍继续增高（Ｐ＜０.０１）;与之不同的是ＩＬ－４基因,在ＣＬＰ后３h ＩＬ－４基因表达与sham组差异无显著意义,至ＣＬＰ后１２h才明显高于sham组（Ｐ＜０.０１）。ＣＬＰ后３h肝组织含水量与肝微血管通透性即开始有所升高但与sham组比较差异无显著意义,至ＣＬＰ后１２h进一步增高与sham组比较差异均有显著意义（含水量Ｐ＜０.０５,微血管通透性Ｐ＜０.０１）。结论 促炎症细胞因子与抗炎症细胞因子之间力量对比的失衡可能是脓毒症并发肝损伤的重要原因。     

结直肠癌患者手术前后血清sIL—2R和TNF水平的检测及临床意义

采用双抗体夹心ＥＬＩＳＡ法，对６９例结直肠癌（ＣＲＣ）患者手术前后血清可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）和肿瘤坏死因子（ＴＮＦ）水平进行了动态观察，结果表明：①结直肠癌患者血清ｓＩＬ－２Ｒ和ＴＮＦ水平均明显高于正常对照组（Ｐ〈０．０１）；②结直肠Ｄｕｋｅｓ分期Ｃ期和Ｄ期的ｓＩＬ－２Ｒ和ＴＮＦ水平均明显高于Ａ期和Ｂ期（Ｐ〈０．０５）；③结直肠癌患者手术后１个月；血清ｓＩＬ－２Ｒ和ＴＮＦ水平均显     

不同种类透析膜对单个核细胞激活产生细胞因子的影响

目的 了解不同种类透析膜对外周血单个核细胞（ＰＢＭＣ）产生白细胞介素－１β（ＩＬ－１β）、肿瘤坏死因子α（ＴＮＦα）、ＩＬ－６的影响。方法 分离培养ＰＢＭＣ，用放射免疫（ＲＩＡ）法测定培养上清液中ＩＬ－１β、ＴＮＦα、ＩＬ－６。结果 用铜仿（ＣＵ）膜透析，透前ＰＢＭＣ产生的ＩＬ－１β、ＴＮＦα、ＩＬ－６高于对照组；其次是聚甲基丙烯酸甲脂膜（ＰＭＭＡ）膜和ＨＥ膜。透析过程中ＰＢＭＣ产生的细胞因子都明     

IL-6、IL-1和PDGF对大鼠肾小球系膜细胞生长的影响

目的：探讨白细胞介素－６（ＩＬ－６）、白细胞介素－１（ＩＬ－１）和血小板源生长因子（ＰＤＧＦ）对大鼠肾小球系膜细胞（ＭｓＣ）增殖的影响。方法：采用改良的ＭＴＴ法和ＢｒｄＵ掺入法检测ＳＤ大鼠体外ＭｓＣ悬液中加入ＩＬ－６、ＩＬ－１及ＰＤＧＦ后１２ｈ及２４ｈ的增殖情况。分７组进行观察。结果：ＩＬ－６组、ＩＬ－１组和ＰＤＧＦ组１２ｈ及２４ｈ的光密度（ＯＤ值）与标记指数（ＬＩ）均为２％ＦＣＳ组也均高,但所有实验组均不能达２０％ＦＣＳ组的细胞增殖水平。联合应用双因子刺激１２ｈ及２４ｈ均未见明显的协同促增殖作用。结论：ＩＬ－６、ＩＬ－１及ＰＤＧＦ均能在一定程度上刺激大鼠肾小球ＭｓＣ增生。联合应用双因子刺激无明显的协同效应。     

妇科肿瘤患者血清中细胞因子的表达及意义

目的：研究妇科肿瘤患者血清中细胞因子的变化,探索与发展机理的相关性,方法;以双抗体夹心ＥＬＩＳＡ法对７９例阳性妇科肿瘤患者血清中肿瘤坏死因子（ＴＮＦ－α）,白细胞介素－６（ＩＬ－６）,白细胞介素－８（ＩＬ－８）和白细胞介素－１０（ＩＬ－１０）水平进行了监测。结果：妇科恶性肿瘤组ＴＮＦ－α,ＩＬ－６,ＩＬ－８和ＩＬ－１０水平均明显高于正常对照组和妇科良性肿瘤组（Ｐ〈０．０１）,其中尤以卵巢癌增减最国     

人胆囊组织内巨噬细胞、肿瘤坏死因子、IL-1的含量变化与胆结石的关系

收集人体胆囊６３份，其中１６份无结石为非结石组，４７份为有胆固醇结石之胆囊为结石组。测定胆囊组织巨噬细胞（Ｍ）数量、胆囊粘膜肿瘤坏死因子（ＴＮＦ）、白细胞介素－１（ＩＬ－１）的含量。结果：结石组胆囊组织内Ｍ数量明显高于非结石组（分别为４１０１．９０±２９５．７２、５７２．１３±３０．０７ＡＵ，Ｐ＜０．０１）；结石组胆囊粘膜ＴＮＦ、ＩＬ－１的含量亦显著高于非结石组（ＴＮＦ分别为１８．１２±２．０３、４．４５±０．３９ｎｇ／ｍｇ，Ｐ＜０．００１。ＩＬ－１分别为１０２．４２±７．８４、６６．７５±９．５０ｕ／ｍｇ蛋白，Ｐ＜０．０５）。结果提示：胆囊组织Ｍ中的活化及其释放的ＴＮＦ、ＩＬ－１与胆囊组织炎症反应和胆囊结石的形成有内在联系。     

前列腺素E1对C—BSA原位肾炎血清白细胞介素1,肿瘤坏死因子…

探讨了炎性细胞因子白细胞介素１（ＩＬ－１）和肿瘤坏死因子（ＴＮＦ）在大鼠Ｃ－ＢＳＡ肾炎中的变化及加用外源性前列腺素Ｅ１（ＰＧＥ１）对这些因子的调节作用。结果表明：Ｃ－ＢＳＡ肾炎模型血清ＩＬ－１和ＮＴＦ均较对照明显升高。加用ＰＧＥ１则明显抑制ＩＬ－１和ＴＮＦ活性水平并改善血栓素－前列环素平衡，同时２４小时尿蛋白定量显著下降，肾脏病理变化减轻。结果提示：ＩＬ－１、ＴＮＦ在肾炎发病机理中可能起了重要作用     

重度创伤后血清肿瘤坏死因子α及白细胞介素6水平变化与感？…

目的 探讨严重创伤后血清肿瘤坏死因子α（ＴＮＦ－α）和白细胞介素６（ＩＬ－６）水平的变化与感染性并发症的相关性。方法 选择８０例重度多发性创伤患者，动态观察创伤当日，伤后第３、１０、２０天及出院前血清ＴＮＦ－α、ＩＬ－６的变化。结果 血清ＴＮＦ－α水平的变化与严重感染发生率之间的相关系数ｒ＝０．９０９５，Ｐ〈０．０１；血清ＩＬ－６水平的变化与严重感染发生率之间的相关系数ｒ＝０．９７７０，Ｐ〈０．０     

地塞米松对创伤性急性肺损伤家兔肿瘤坏死因子-α的干预作用

目的 探讨地塞米松（Ｄｅｘ）对创伤性急性肺损伤（ＡＬＩ）治疗作用的可能机制。方法 采用逆转录聚合酶链反应（ＲＴ－ＰＣＲ）、酶联免疫吸附法（ＥＬＩＳＡ）检测２４只大耳白兔肺组织肿瘤坏死因子－α基因（ＴＮＦ－αｍＲＮＡ）表达及肺泡巨噬细胞（ＡＭ）培养上清液中肿瘤坏死因子－α（ＴＮＦ－α）、白细胞介素（ＩＬ）－６水平。结果 创伤性ＡＬＩ兔肺组织ＴＮＦ－αｍＲＮＡ表达及ＡＭ培养上清液中ＴＮＦ－α,ＩＬ－６含量较正常对照组比较明显升高（Ｐ〈０．０１）。Ｄｅｘ治疗后能显著下调ＴＮＦ－αｍＲＮＡ的表达（６８％,Ｐ〈０．０１）,降低ＡＭ分泌ＴＮＦ－α（Ｐ〈０．０５）及ＩＬ－６水平（Ｐ〈０．０１）。结论 Ｄｅｘ能缓解创伤性ＡＬＩ的发生、发展。其机制与其对ＴＮＦ－α、ＩＬ－６等炎性介质的调节作用密切相关。     

前列腺素E_1对C－BSA原位肾炎血清白细胞介素1、肿瘤坏死因子及病理变化的调节

探讨了炎性细胞因子白细胞介素１（ＩＬ－１）和肿瘤坏死因子（ＴＮＦ）在大鼠Ｃ－ＢＳＡ肾炎中的变化及加用外源性前列腺素Ｅ＿１（ＰＧＥ＿１）对这些因子的调节作用。结果表明：Ｃ－ＢＳＡ肾炎模型血清ＩＬ－１和ＴＮＦ均较对照明显升高。加用ＰＧＥ＿１则明显抑制ＩＬ－１和ＴＮＦ活性水平并改善血栓素一前列环素平衡，同时２４小时尿蛋白定量显著下降，肾脏病理变化减轻。结果提示：ＩＬ－１、ＴＮＦ在肾炎发病机理中可能起了重要作用，外源性ＰＧＥ＿１可以抑制其产生和释放并缓解病情发展。     

右美托咪啶对脓毒症大鼠血清炎性因子和氧化应激反应的影响

目的 探讨右美托咪啶对脓毒症大鼠血清炎性因子和氧化应激反应的影响.方法 健康雄性SD大鼠30只,10～ 14周龄,体重250～300 g,采用随机数字表法,将其随机分为3组(n=10):假手术组(S组)、脓毒症组(CLP组)和脓毒症+右美托咪啶组(CLP+D组).CLP组和CLP+D组采用盲肠结扎穿孔术制备脓毒症模型,CLP+D组术毕静脉输注右美托咪啶10 μg·kg-1·h-1至大鼠死亡或术后12 h,S组和CLP组给予等容量生理盐水1ml·kg-1·h-1.每组取5只大鼠,分别于术前(基础状态)、术后1、6、12 h时采集股动脉血样,测定血清IL-6、IL-10、SOD及MDA的水平.记录术后12 h内大鼠生存情况.结果 与S组比较,CLP组术后1、6、12 h时血清IL-6、IL-10和MDA的浓度升高,血清SOD活性和生存率降低(P＜0.05);与CLP组比较,CLP+D组术后6、12 h时血清IL-6和MDA的浓度降低,术后12 h时血清SOD活性和生存率升高(P＜0.05).结论 右美托咪啶可以提高脓毒症大鼠的生存率,其机制与抑制炎性因子释放及氧化应激反应有关.     

脂联素对脓毒症大鼠早、晚期炎症介质表达的影响

目的 研究脂联素(adiponectin,APN)对内毒素(lipopolysaccharide,LPS)诱导的脓毒症大鼠早、晚期炎症介质表达的影响.方法 将96只健康雄性Wistar大鼠按随机数字表法分为4组(每组24只):对照组(C组)、模型组(LPS组)、APN预处理组(APN+LPS组)及APN后处理组(LPS...     

The complex pattern of cytokines in sepsis. Association between prostaglandins, cachectin, and interleukins.

Although the cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) are important mediators of hemodynamic, metabolic, and immunologic alterations in the host during sepsis, it is not known whether there is any association between the release of these cytokines and prostanoids during sepsis. Sepsis induced by cecal ligation and puncture in rats led to a persistent elevation (p less than 0.05) of plasma TNF until 10 hours, steadily increasing (p less than 0.05) IL-1 plasma levels, and enhanced (p less than 0.05) IL-6 plasma levels at all time points compared to the sham group. Prostaglandin E2 plasma levels were elevated (p less than 0.05) at 5 hours (153 +/- 29 pg/mL; control: 47 +/- 11 pg/mL) and 10 hours (96 +/- 16 pg/mL; control: 21 +/- 5 pg/mL). Prostaglandin E2 production by splenic macrophages (sM phi) from septic animals was increased (p less than 0.05) at 5 hours (9.1 +/- 2.2 ng/mL) and 10 hours (5.6 +/- 1.5 ng/mL) compared to controls (3.3 +/- 0.3 ng/mL at 5 hours; 1.3 +/- 1.3 ng/mL at 10 hours). Incubation of sM phi from septic animals with ibuprofen enhanced (p less than 0.05) IL-1 and TNF synthesis, while IL-6 production was reduced (p less than 0.05). These results indicate that the alterations in prostanoid release and elevated plasma prostanoids may regulate the release and consequently the circulating levels of cytokines during sepsis.     

Recombinant interleukin-1 receptor antagonist (IL-1ra): effective therapy against gram-negative sepsis in rats.

BACKGROUND. Morbidity and mortality from bacterial sepsis remain high despite aggressive diagnostic and therapeutic intervention. Interleukin-1 has been implicated as mediator of the lethal effects of endotoxemia or bacterial sepsis. The current experiments were designed to evaluate the therapeutic efficacy of a human recombinant interleukin-1 receptor antagonist (IL-1ra) against polymicrobial gram-negative septicemia in rats. METHODS. Male rats underwent placement of indwelling carotid arterial and superior vena caval catheters followed by cecal ligation and puncture (CLP). After 3 hours rats received either IL-1ra (10 mg/kg intravenous bolus followed by 5 mg/kg/hr) or an equal volume of vehicle intravenously for 24 hours. Heart rate, respirations, mean arterial blood pressure, and temperature were recorded at frequent intervals, and survival was assessed for 30 hours after CLP. RESULTS. There were no differences in vital signs between groups at baseline or before treatment, and all animals appeared ill with huddled posture, piloerection, and hyperventilation. Twenty-four hours after CLP, IL-1ra significantly ameliorated bradycardia (p = 0.01), hypothermia (p = 0.001), and hypotension (p = 0.05), and 30-hour survival was significantly improved (71% vs 20%, p less than 0.05). CONCLUSIONS. IL-1ra lessens the acute hemodynamic, hypothermic, and mortal effects of gram-negative sepsis induced by CLP in rats. These data suggest that IL-1 receptor blockade may be an important new treatment strategy against overwhelming bacterial sepsis.     

胸腺肽α1对严重腹腔感染大鼠免疫功能及蛋白质代谢的影响

目的观察腹腔感染后胸腺肽α1(Tα1)对大鼠免疫功能及蛋白质代谢的影响。方法采用盲肠结扎加穿孔(CLP)大鼠模型,观察腹腔感染后Tα1对血浆T细胞亚群、肿瘤坏死因子α(TNFα)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、白蛋白、C反应蛋白(CRP)水平及大鼠病死率的变化。结果腹腔感染后大鼠血浆TNFα、IL-6浓度明显高于对照组,IL-10浓度明显低于对照组;给予Tα1后血浆TNFα、IL-6浓度亦明显高于对照组,但TNFα、IL-6较感染组明显下降,IL-10较感染组明显上升;给予Tα1后CD3、CD4百分率和CD4／CD8明显高于感染组;用Tα1后血白蛋白下降较腹腔感染组明显减轻;血C反应蛋白(CRP)浓度感染组和感染后用Tα1组明显升高,但给予Tα1后CRP升高的程度较感染组明显减轻;7天累积死亡率亦较感染组明显减少。结论胸腺肽α1可改善严重腹腔感染大鼠的免疫功能、炎性反应和蛋白质代谢。     

Inhibition of macrophage-activating cytokines is beneficial in the acute septic response.

Interferon-gamma and other cytokines enhance macrophage (M phi) antimicrobial function and have been considered for therapeutic use in sepsis. Systemic sequelae of macrophage activation, however, are unclear. This study examined the effects of M phi activating cytokines (interferon-gamma [IFN-gamma] and interleukin-4 [IL-4]) and monoclonal antibodies directed against these cytokines in modulating the acute septic response. CFW/Swiss Webster mice (n = 345) received endotoxin (lipopolysaccharide [LPS]: 60 mg/kg body weight intraperitoneally) and were randomized to five treatment groups: IFN-gamma (10(4) units), IL-4 (10(4) units), IgG1 isotype antibody (TRFK5: 200 micrograms), anti-IFN-gamma (200 micrograms), or anti-IL-4 (200 micrograms) monoclonal antibodies (MAbs) given simultaneously or 2 hours after LPS. Animals were divided into two groups and studied for mortality or measurement of peritoneal M phi superoxide anion release (O2-), tumor necrosis factor (TNF), and IL-6 production 6 hours after administration of LPS +/- experimental regimens. Serum TNF and IL-6 also were assessed at 2 and 4 hours after LPS, respectively. Administration of LPS resulted in a 27% survival compared with 10% in the IFN-gamma and 13% in the IL-4 groups. Treatment with anti-IFN-gamma offered protection against LPS lethality (93%-100% survival, p less than 0.001 vs. other groups) when given either simultaneously or 2 hours after LPS. Anti-IFN-gamma also significantly decreased PM phi O-2 and TNF release. Thus anti-IFN-gamma may have an important role in the modulation of the acute septic response.     

丙酮酸乙酯对脓毒症大鼠肠组织保护和HMGB1表达的影响

目的:通过观察丙酮酸乙酯对脓毒症大鼠肠组织HMGB1表达的影响,进一步揭示丙酮酸乙酯治疗脓毒症的分子作用机制。方法:将96只SD大鼠随机分为假手术组、脓毒症组、低剂量丙酮酸乙酯治疗组(LET组)、高剂量丙酮酸乙酯治疗组(ET组),以盲肠结扎穿刺法复制大鼠脓毒症模型。LET组(20 mg/kg)及ET组(40 mg/kg)即刻腹腔内注射EP注射液4 mL,每6 h重复注射一次,直至实验结束,假手术组及脓毒症组在相同时间用相同剂量的生理盐水腹腔内注射。各组大鼠分别于术后2 h、8 h、24 h、48 h 4个时间点随机处死6只大鼠,经腹主动脉取血,用ELISA方法检测血浆TNF-α、IL-6、HMGB1水平。术后24 h,取大鼠末端回肠,用RT-PCR法检测回肠组织HMGB1mRNA表达水平,用免疫组织化学两步方法观察肠组织HMGB1蛋白表达,在光镜下观察大鼠肠组织的病理变化。结果:与假手术组相比,脓毒症组血浆HMGB1在术后8 h、24 h、48 h显著增高,脓毒症组回肠组织HMGB1mRNA及蛋白表达在术后24 h显著增高(P0.05)。与脓毒症组相比,ET组、LET组血浆HMGB1在术后8 h、24 h、48 h显著降低,ET组、LET组回肠组织HMGB1mRNA及蛋白表达在术后24h显著降低(P0.05)。结论:脓毒症大鼠血浆HMGB1出现时间晚,作用时间长,提示HMGB1是脓毒症的重要晚期炎症介质。丙酮酸乙酯可抑制脓毒症大鼠血浆及肠组织HMGB1的表达,提示丙酮酸乙酯对脓毒症的治疗机制可能与其直接或间接抑制HMGB1的表达有关。     

Sepsis induces an early increased spontaneous release of hepatocellular stimulatory factor (interleukin-6) by Kupffer cells in both endotoxin tolerant and intolerant mice.

Previous studies have shown that hepatocellular function is significantly depressed early during sepsis and that this is associated with a marked increase in the circulating levels of the hepatocellular stimulatory factor (IL-6). It remains unknown, however, whether or not Kupffer cells (KC) are activated during sepsis and whether these cells are the major contributors to the increased circulating levels of this cytokine. The objectives of this study were, therefore, to determine whether or not during sepsis: (1) KC are stimulated in vivo to release IL-6, as compared to other cytokines; (2) KC differ from splenic macrophages (SM phi) in their ability to release cytokines; and (3) there is a difference in macrophage (M phi) cytokine release between endotoxin (ET)-tolerant (C3H/HeJ) and ET-intolerant (C3H/HeN) mice. To assess this, KC and SM phi were harvested at 1 or 24 hr from mice which had been subjected to polymicrobial sepsis by cecal ligation and puncture (CLP) or sham-operation. Following depletion of the nonadherent cells, KC and SM phi cultures were incubated for 24 hr in the presence or absence of 10 micrograms of ET/ml, and the levels of interleukin (IL)-1, IL-6, and TNF release were determined by bioassays. Sepsis induced an early (at 1 hr) in vivo stimulation of KC but not SM phi IL-6 release, irrespective of ET-tolerance/intolerance. However, the release of IL-1 or TNF was not markedly different for either CLP or sham KC.(ABSTRACT TRUNCATED AT 250 WORDS)