血清炎性因子浓度对急性脑出血恶化的预测价值

目的揭示和比较血清C-反应蛋白、白介素-1β、白介素．6、肿瘤坏死因子-α浓度对脑出血急性期早期神经功能恶化的预测价值。方法选取86例急性基底节区出血患者作为病例组和86例健康体检者作为对照组。记录脑出血患者入院时血肿量、脑室出血、NIHSS评分及早期神经功能恶化等临床资料。采用ELISA法测定血清C-反应蛋白、白介素-1β、白介素-6、肿瘤坏死因子-α浓度。统计分析这些炎性因子对早期神经功能恶化的预测价值。结果经独立样本t检验,病例组（或脑室出血患者或早期神经功能恶化患者）血清C-反应蛋白、白介素-1β、白介素-6、肿瘤坏死因子．仅浓度均较对照组（或非脑室出血患者或非早期神经功能恶化患者）明显增高（均P〈0．05）。行Pearson相关检验,人院时血肿量及NIHSS评分与血清C-反应蛋白、白介素-1β、白介素-6、肿瘤坏死因子．仪浓度均显著正相关性（均P〈0．05）。ROC曲线分析显示,血清C-反应蛋白、白介素-1β、白介素-6、肿瘤坏死因子．d浓度对急性期早期神经功能恶化均有显著预测价值,且它们的曲线下面积比较,差异均无统计学意义（均P〉0．05）。结论C-反应蛋白、白介素-113、白介素-6、肿瘤坏死因子．理可能参与脑出血急性期早期神经功能恶化的炎症反应过程,临床检测这些因子可更好预测早期神经功能恶化的发生。     

神经生长因子对大鼠脑缺血再灌注损伤的神经保护

目的探讨神经生长因子（NGF）对大鼠局灶性脑缺血再灌注损伤的保护作用。方法线栓法建立大鼠右侧大脑中动脉缺血-再灌注损伤模型,同时给予NGF治疗。检测肿瘤坏死因子-α（TNF-α）、自介素-1（IL-1）、白介素-6（IL-6）,丙二醛（MDA）及超氧化物歧化酶（SOD）含量及神经细胞的凋亡数。结果NGF组TNF-α、IL-1较缺血再灌注损伤（IR）组明显下降,差异有统计学意义。与IR组相比,NGF组SOD活性明显升高、MDA及IL-6含量明显下降,差异有统计学意义。神经细胞的凋亡检测发现,与IR组比较,NGF组凋亡细胞数明显降低,差异有统计学意义。结论NGF可以减轻炎症反应和改善氧自由基代谢,减少脑组织细胞的凋亡,对局灶性脑缺血再灌注损伤大鼠具有保护作用。     

白术内酯Ⅲ调节AMPK/SIRT1/NF-κB信号通路对脓毒症大鼠肝损伤的影响

目的 探究白术内酯Ⅲ(AtractylideneⅢ，Atr-Ⅲ)对脓毒症大鼠肝损伤的影响以及对腺苷酸激活蛋白激酶(AMPK)/去乙酰化酶1(SIRT1)/核因子-κB(NF-κB)信号通路的调节作用。方法 将60只SPF级SD雄性大鼠分为假手术组、模型组、阳性组、Atr-Ⅲ低、高剂量组、Atr-Ⅲ高剂量+AMPK抑制剂组。检测大鼠血清中谷草转氨酶(AST)、谷丙转氨酶(ALT)水平；苏木素-伊红(HE)染色观察肝组织的病理变化；TUNEL染色检测肝细胞凋亡情况；ELISA检测血清白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平；检测肝组织超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性；Western blot检测通路相关蛋白表达情况。结果 与假手术组相比，模型组大鼠肝细胞损伤严重，AST、ALT、IL-1β、IL-6、TNF-α水平、细胞凋亡率、p65 NF-κB磷酸化表达均升高，SOD、CAT活性、AMPK磷酸化、SIRT1蛋白表达均降低(P <0.05)；与模型组相比，阳性组和Atr-Ⅲ组大鼠肝细胞形态恢复，AST、ALT、IL-...     

高血压脑出血患者血清炎性因子变化与其病情的相关性研究

目的:通过测定高血压脑出血患者血清C-反应蛋白、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、同型半胱氨酸及NF-κB水平变化,探讨炎性因子与高血压脑出血的相关性.方法:选取高血压脑出血患者75例(实验组),静脉采取血液,检测血清C-反应蛋白、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、同型半胱氨酸及NF-κB的含量,并与30例正常体检患者(对照组)对比.结果:实验组患者静脉血清C-反应蛋白、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、同型半胱氨酸及NF-κB含量明显高于对照组.结论:高血压脑出血患者血清C-反应蛋白、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、同型半胱氨酸及NF-κB参与了脑出血炎性反应,是脑出血脑组织损伤的重要作用机制之一.     

连续性血液净化对重症急性胰腺炎疗效及炎症因子的影响

目的:探究连续性血液净化对重症急性胰腺炎患者血清肿瘤坏死因子-α、白介素-1β、白介素-6水平的影响。方法:选取2017年3月～2019年4月就诊的46例重症急性胰腺炎患者为研究对象,按照随机数字表法分为对照组和研究组,各23例。对照组给予常规治疗,研究组在对照组治疗基础上给予连续性血液净化治疗。比较两组血清肿瘤坏死因子-α、白介素-6、白介素-1β水平及腹胀消失时间、腹痛消失时间和住院时间等临床指标。结果:治疗3 d后,两组肿瘤坏死因子-α、白介素-6、白介素-1β水平均降低,且研究组各指标水平均低于对照组(P0.05);研究组腹胀、腹痛消失时间和住院时间均显著短于对照组(P0.05)。结论:连续性血液净化可有效降低重症急性胰腺炎患者血清肿瘤坏死因子-α、白介素-6、白介素-1β水平,降低机体炎症反应,促进康复。     

左西孟旦改善大鼠心肺复苏后急性肾损伤的机制研究

目的探索左西孟旦在改善大鼠心肺复苏后急性肾损伤中的机制。方法将25只健康成年雄性SD大鼠采用随机数字表法分为左西孟旦治疗组(治疗组, 10只)、实验组(10只)和对照组(5只)。治疗组和实验组采用窒息法建立心脏骤停-心肺复苏模型, 治疗组在复苏期间及复苏后予以左西孟旦干预, 实验组在复苏期间及复苏后予以等剂量生理盐水处理, 对照组不进行心脏骤停和心肺复苏操作, 予以等剂量生理盐水处理。复苏6 h后将3组大鼠处死, 检测大鼠血清中肌酐(serum creatinine, Scr)、尿素氮(blood urea nitrogen, Bun)、白介素-1β(interleukin-1β, IL-1β)、白介素-6(interleukin-6, IL-6)和肿瘤坏死因子α(tumor necrosis factor-α, TNF-α), HE染色观察肾脏组织损伤情况, 同时采用Paller评分量化肾脏损伤情况, TUNEL法检测凋亡, Western印迹检测磷酸化的细胞外调节蛋白激酶(phosphorylated extracellular regulated protein kinases,...     

肿瘤坏死因子α诱导大鼠成骨细胞凋亡与中药骨康的干预效应形态学观察

目的:观察能诱导体外培养的破骨细胞凋亡的骨康含药血清对新生大鼠成骨细胞凋亡的抑制作用。方法:实验于2003-01/2003-06在广州中医药大学第一附属医院骨科实验室完成。①选用1d龄雌性SD大鼠3只,用于分离原代成骨细胞;6月龄SD雌性大鼠24只用于制备含药血清。②6月龄SD雌性大鼠随机分成3组,每组8只,分别为骨康方组、罗盖全组和空白对照组(蒸馏水灌胃)。骨康方由淫羊藿、补骨脂、黄芪、熟地、白芍等药物组成,为中药煎剂,含生药量1.43kg/L,按4.8g/kg生药灌胃,相当于临床剂量的10倍。罗盖全(活性维生素D3)按0.084μg/kg灌胃,相当于临床剂量的10倍。各组大鼠分别用上述物质灌胃,每次17.5mL/kg,2次/d,间隔5h,连续灌胃3d,最后1次灌胃后2h腹主动脉取血,离心获取含药血清。将传代的成骨细胞分别加入含药血清培养7d时,加入肿瘤坏死因子α,剂量为30μg/L,分别于12和24h后取出长有成骨细胞的盖玻片,经吖啶橙染色,置Nikon荧光显微镜下直接观察拍照。③成骨细胞的鉴定,包括形态学观察和碱性磷酸酶染色和矿化结节茜素红染色观察。结果:①在用空白血清培养7d的成骨细胞中加入肿瘤坏死因子α,12h时可见到成骨细胞出现凋亡征象,24h时出现典型的细胞凋亡形态。②在用骨康血清和罗盖全血清培养7d的成骨细胞可部分对抗肿瘤坏死因子α所致的成骨细胞凋亡作用,中药骨康血清和罗盖全血清对成骨细胞凋亡的抑制作用相似。结论:①肿瘤坏死因子α可诱导成骨细胞凋亡。②用中药骨康含药血清培养7d的成骨细胞可部分对抗肿瘤坏死因子α对其的损伤,提示中药骨康可通过阻滞肿瘤坏死因子α诱导的成骨细胞凋亡,发挥防治骨质疏松的作用。     

银杏内酯B对脑缺血-再灌注神经元损伤的保护作用

目的:研究银杏内酯B对大鼠脑缺血-再灌注神经元损伤的干预作用及其可能机制.方法:采用Kameyama的3条动脉夹闭法制备大鼠脑缺血-再灌注损伤模型.45只Wistar大鼠随机分成假手术对照组、缺血-再灌注模型组、生理盐水对照组和银杏内酯B预处理组;测定各组动物脑匀浆液中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和ATP酶活性以及丙二醛(MDA)含量,并观察脑组织的病理学改变和细胞凋亡指数.结果:全脑缺血-再灌注可引起SOD、GSH-Px和ATP酶活性明显下降,MDA含量显著升高;脑组织呈现炎症性改变,层次不清,细胞凋亡指数达(40.2±6.3)%.银杏内酯B(1～10 mg/kg)能剂量依赖性地降低MDA水平,提高SOD、GSH-Px和ATP酶活性(P<0.05或P<0.01),明显减轻脑组织神经细胞损害,减少细胞凋亡发生率.结论:银杏内酯B对大鼠脑缺血-再灌注神经元损伤具有明显的保护作用,其机制可能是通过减少自由基的产生和增强ATP酶活性.     

落新妇甙对肝缺血再灌注损伤的保护作用

背景:肝脏是对缺血再灌注损伤最敏感的器官之一。黄酮类化合物落新妇甙可作为递氢体清除氧自由基,从而可能在减轻肝脏缺血再灌注损伤等方面发挥作用。目的:观察落新妇甙对肝脏热缺血再灌注损伤的保护作用,对其机制进行初步探讨。方法:C57BL/6小鼠随机分为4组:假手术组、模型组、小剂量干预组和大剂量干预组。干预组小鼠于缺血前24h和1h分别给予10或40mg/kg的落新妇甙腹腔注射,然后建立70%部分肝缺血再灌注模型。采集血液和肝脏组织样本。检测血清丙氨酸氨基转移酶活性,ELISA测血清肿瘤坏死因子α水平,化学比色法测定肝组织中超氧化物歧化酶、丙二醛含量。肝脏组织病理学检测。Westernblot检测肝组织中肿瘤坏死因子α蛋白含量,RT-PCR检测肿瘤坏死因子αmRNA。结果与结论:落新妇甙干预能有效降低血清丙氨酸氨基转移酶水平,干预组肝组织丙二醛含量较模型对照组明显下降(P<0.01);而超氧化物歧化酶含量明显上升(P<0.01);干预组血清肿瘤坏死因子α含量较模型组对照组明显下降(P<0.01);小、大剂量干预组肝组织中肿瘤坏死因子α蛋白表达与模型组模型对照组比较渐次降低,与半定量RT-PCR结果相符(小剂量干预组P<0.05,大剂量干预组P<0.01)。落新妇甙保护肝脏热缺血再灌注损伤显示出剂量-效应关系趋势。结果提示,落新妇甙干预能减轻小鼠肝脏热缺血再灌注损伤后的炎症反应和脂质过氧化损伤,有效改善肝功能和肝脏病理损害;机制可能在于其能抑制缺血再灌注损伤肝组织中肿瘤坏死因子α的高表达。     

落新妇甙对肝缺血再灌注损伤的保护作用

背景：肝脏是对缺血再灌注损伤最敏感的器官之一。黄酮类化合物落新妇甙可作为递氢体清除氧自由基,从而可能在减轻肝脏缺血再灌注损伤等方面发挥作用。目的：观察落新妇甙对肝脏热缺血再灌注损伤的保护作用,对其机制进行初步探讨。方法：C57BL/6小鼠随机分为4组：假手术组、模型组、小剂量干预组和大剂量干预组。干预组小鼠于缺血前24h和1h分别给予10或40mg/kg的落新妇甙腹腔注射,然后建立70%部分肝缺血再灌注模型。采集血液和肝脏组织样本。检测血清丙氨酸氨基转移酶活性,ELISA测血清肿瘤坏死因子α水平,化学比色法测定肝组织中超氧化物歧化酶、丙二醛含量。肝脏组织病理学检测。Westernblot检测肝组织中肿瘤坏死因子α蛋白含量,RT-PCR检测肿瘤坏死因子αmRNA。结果与结论：落新妇甙干预能有效降低血清丙氨酸氨基转移酶水平,干预组肝组织丙二醛含量较模型对照组明显下降（P〈0.01）;而超氧化物歧化酶含量明显上升（P〈0.01）;干预组血清肿瘤坏死因子α含量较模型组对照组明显下降（P〈0.01）;小、大剂量干预组肝组织中肿瘤坏死因子α蛋白表达与模型组模型对照组比较渐次降低,与半定量RT-PCR结果相符（小剂量干预组P〈0.05,大剂量干预组P〈0.01）。落新妇甙保护肝脏热缺血再灌注损伤显示出剂量-效应关系趋势。结果提示,落新妇甙干预能减轻小鼠肝脏热缺血再灌注损伤后的炎症反应和脂质过氧化损伤,有效改善肝功能和肝脏病理损害;机制可能在于其能抑制缺血再灌注损伤肝组织中肿瘤坏死因子α的高表达。     

白藜芦醇调控体外培养人骨关节炎滑膜细胞白细胞介素18的表达

背景：白藜芦醇可在体外抑制软骨细胞的凋亡。目的：观察白藜芦醇对体外培养人骨关节炎滑膜细胞中白细胞介素18、白细胞介素1β和肿瘤坏死因子α表达的影响。方法：对兔以白藜芦醇临床等效剂量灌胃后,制备含10%,20%,40%白藜芦醇含药血清,与人骨关节炎滑膜细胞共培养,以正常兔血清培养细胞为对照。结果与结论：ELISA检测及免疫细胞化学检测结果显示,不同浓度白藜芦醇含药血清组体外培养滑膜细胞白细胞介素18、白细胞介素1β、肿瘤坏死因子α分泌量较正常兔血清组明显降低（P〈0.01）,并随白藜芦醇浓度的增加,白细胞介素18、白细胞介素1β、肿瘤坏死因子α分泌量逐渐降低（P〈0.01或P〈0.05）。白细胞介素1β、肿瘤坏死因子α水平依次与白细胞介素18水平呈正相关。表明白藜芦醇能够显著下调白细胞介素18、白细胞介素1β、肿瘤坏死因子α在骨关节炎滑膜细胞中的表达,减轻滑膜炎症反应。     

Protective effect of crocetin on hemorrhagic shock-induced acute renal failure in rats

Multiple organ failure is a common outcome of hemorrhagic shock followed by resuscitation, and the kidney is one of the prime target organs involved. The main objective of the study was to evaluate whether crocetin, a natural product from Gardenia jasminoides Ellis, has beneficial effects on renal dysfunction caused by hemorrhagic shock and resuscitation in rats. Anesthetized rats were bled to reduce mean arterial blood pressure to 35 (SD, 5) mmHg for 60 min and then were resuscitated with their withdrawn shed blood and normal saline. Crocetin was administered via the duodenum at a dose of 50 mg/kg 40 min after hemorrhage. The increase in creatinine and blood urea nitrogen was significantly reduced at 2 h after hemorrhage and resuscitation in crocetin-treated rats. The increases in renal nitric oxide, tumor necrosis factor α, and interleukin 6 were also attenuated by crocetin. Hemorrhagic shock resulted in a significant elevation in malondialdehyde production and was accompanied by a reduction in total superoxide dismutase activity, activation of nuclear factor κB, and overexpression of inducible nitric oxide synthase. These changes were significantly attenuated by crocetin at 2 h after resuscitation. These results suggested that crocetin blocks inflammatory cascades by inhibiting production of reactive oxygen species and restoring superoxide dismutase activity to ameliorate renal dysfunction caused by hemorrhage shock and resuscitation.     

Effect of sesame oil on oxidative-stress-associated renal injury in endotoxemic rats: involvement of nitric oxide and proinflammatory cytokines

This study aimed to investigate the effect of sesame oil on oxidative stress-associated renal injury induced by lipopolysaccharide in rats. The effects of sesame oil on renal injury, oxidative stress, hydroxyl radical, superoxide anion, nitric oxide, and proinflammatory cytokines were assessed after a lipopolysaccharide challenge. Sesame oil attenuated lipopolysaccharide-induced renal injury, decreased lipid peroxidation, increased the activities of superoxide dismutase, catalase, and glutathione peroxidase, reduced hydroxyl radical generation and nitric oxide production, and had no effect on superoxide anion generation in lipopolysaccharide-challenged rats. In addition, sesame oil significantly decreased tumor necrosis factor-alpha and interleukin 1beta production 1 and 6 h, respectively, after lipopolysaccharide administration in mice. Thus, sesame oil attenuates oxidative stress-associated renal injury via reduction of the production of nitric oxide and the generation of proinflammatory cytokines in endotoxemic rats.     

Multifocal necrotizing leukoencephalopathy in septic shock

OBJECTIVE: Multifocal necrotizing leukoencephalopathy, characterized by multiple microscopic foci of necrosis involving the white matter of the pons, has been described mainly after chemotherapy or radiotherapy for brain cancer and in HIV infection. The role of circulating cytokines has been suggested but remains to be assessed. DESIGN: Prospective case series. SETTING: A 26-bed general medical intensive care unit at a university hospital. PATIENTS: Septic shock patients. MEASUREMENTS AND PATIENTS: In three patients who died from septic shock, careful postmortem examination of the brain was performed, including studies of neuronal apoptosis and cytokine expression. MAIN RESULTS: In one patient, typical lesions of multifocal necrotizing leukoencephalopathy were seen. As compared with control 1 and control 2 who did not have multifocal necrotizing leukoencephalopathy, marked lesions of the pons, including vacuolization, apoptosis, microglial activation, and expression of tumor necrosis factor-alpha and interleukin-1beta, were observed in the case. Simultaneously, case 1 had markedly increased circulating levels for tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, interleukin-8, interleukin-10, soluble tumor necrosis factor receptor II, and for interleukin-1 receptor antagonist. CONCLUSION: Septic shock is a newly described cause of multifocal necrotizing leukoencephalopathy, probably mediated by an excessive systemic inflammatory response.     

米力农对顽固性心衰患者心功能及血清TNF-α、IL-6、IL-8水平的影响

[目的]观察米力农对顽固性心衰患者心功能及血清肿瘤坏死因子α(TNF-α)、白介素6(IL-6)、白介素8(IL-8)水平的影响.[方法]30例顽固性心衰患者给与米力农治疗10 d,在治疗前、后分别测定血压、心率、心功能、血清TNF-α、IL-6和IL-8水平,同时与30例健康体检者作对照.[结果]虽然给予米力农治疗后患者的心功能、血清TNF-α、IL-6和IL-8水平与对照组比较仍有显著性差异;但较治疗前有显著改善(P＜0.05).[结论]米力农可以一定程度上地改善顽固性心衰患者的心功能,降低血清TNF-α、IL-6、IL-8水平.     

Effect of endogenous nitric oxide on hyperoxia and tumor necrosis factor-alpha-induced leukosequestration and proinflammatory cytokine release in rat airways

OBJECTIVE: To investigate the effects of endogenous nitric oxide on hyperoxia and tumor necrosis factor-alpha-induced leukosequestration and proinflammatory cytokine release in rat airways. DESIGN: Prospective, randomized, controlled animal study. SETTING: Experimental laboratory. SUBJECTS: Male Sprague-Dawley rats weighing 350-500 g. INTERVENTIONS: The rats were pretreated with N(G)-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) or saline intravenously 4-6 mins before intratracheal administration of tumor necrosis factor-alpha, 95% oxygen, or both, when the vasopressor effect of L-NAME had reached a plateau. MEASUREMENTS AND MAIN RESULTS: Bronchoalveolar lavage fluid was recovered from the airway of rats after exposure to 95% oxygen and tumor necrosis factor-alpha for 6 hrs under ventilator support. Neutrophils in lavage fluid were isolated and examined for the inducible nitric oxide synthase expression by flow-cytometric assay. Tumor necrosis factor-alpha and interleukin-1 beta in lavage fluid were measured by enzyme-linked immunosorbent assay. The percentage of neutrophils in bronchoalveolar fluid was significantly higher in rats exposed to hyperoxia + tumor necrosis factor-alpha (29.7 +/- 12.5%) compared with rats with hyperoxia (16.3 +/- 1.2%), tumor necrosis factor-alpha (4.2 +/- 1.1%), or room air (5.0 +/- 1.8%) alone (p <.05). Rats exposed to hyperoxia + tumor necrosis factor-alpha had significantly higher concentrations of inducible nitric oxide synthase of neutrophils (350.1 +/- 75.7 mean fluorescence intensity), compared with rats with hyperoxia (64.9 +/- 1.6 mean fluorescence intensity), tumor necrosis factor-alpha (102.6 +/- 15.3 mean fluorescence intensity), or room air (111.2 +/- 25.8 mean fluorescence intensity) alone (p <.05). Rats exposed to hyperoxia + tumor necrosis factor-alpha significantly produced higher concentrations of tumor necrosis factor-alpha and interleukin-1 beta, compared with rats with tumor necrosis factor-alpha, hyperoxia, or room air alone. Hyperoxia + tumor necrosis factor-alpha also significantly increased growth-related oncogene/cytokine-induced neutrophil chemoattractant (GRO/CINC)-1 in bronchoalveolar fluid, compared with those receiving tumor necrosis factor-alpha alone, hyperoxia alone, or room air alone. L-NAME significantly enhanced the percentage of neutrophil recovery and the production of tumor necrosis factor-alpha, interleukin-1 beta, and GRO/CINC-1 in airways compared with the corresponding hyperoxia + tumor necrosis factor-alpha treatment alone. CONCLUSIONS: Endogenous nitric oxide may be an important endogenous inhibitor of hyperoxia + tumor necrosis factor-alpha-induced leukocyte recruitment and subsequently tumor necrosis factor-alpha, interleukin-1 beta, and GRO/CINC-1 release.     

Bicuculline methiodide attenuates hepatic injury and decreases mortality in septic rats: role of cytokines

Bicuculline methiodide attenuates inflammation by inhibiting the production of proinflammatory cytokines, such as tumor necrosis factor-alpha, and by increasing the production of the anti-inflammatory cytokine interleukin-10, both of which play important roles in the pathogenesis of sepsis. The aim of this study was to examine the effects of bicuculline methiodide on sepsis in the cecal ligation and puncture septic-rat model. Cytokine production was measured by enzyme-linked immunosorbent assay. Oxidative stress was assessed by determining serum lipid peroxidation and nitrite levels. Hepatic injury was evaluated by determining the levels of serum aspartate aminotransferase, alkaline phosphatase, and total bilirubin. Mortality was recorded within 24 h. Bicuculline methiodide potently decreased the production of tumor necrosis factor-alpha and interleukin-1beta but increased interleukin-10 in serum. Bicuculline methiodide significantly decreased serum lipid peroxidation and nitrite levels. Further, bicuculline methiodide attenuated hepatic injury and reduced mortality after cecal ligation and puncture. Therefore, the alteration of cytokine production may be involved in the effects of bicuculline methiodide on hepatic injury and mortality in septic rats.     

大鼠脑出血血肿周围神经细胞的另类死亡方式——胀亡

目的通过建立大鼠脑出血动物模型观察脑出血后血肿周围神经细胞胀亡时程表达变化。方法48只大鼠随机分为两组：脑出血组和对照组,脑出血组尾状核注入自体血50μL,对照组注入等量生理盐水。分别于6h、24h、2d、3d、5d、7d后处死,根据Rosenberg评分对各组大鼠进行评分,电镜下观察神经细胞胀亡及凋亡形态学变化并计数胀亡神经元。结果脑出血组大鼠神经功能评分24h最高,血肿周围存在胀亡神经元,且胀亡指数24h达高峰,以后逐渐下降,与对照组相比有统计学差异。结论脑出血后存在神经细胞胀亡,且有一定时空变化规律。     

Effect of ciprofloxacin on lethal and sublethal challenge with endotoxin and on early cytokine responses in a murine in vivo model

The influence of ciprofloxacin on immune responses has been suggested by results of in vitro and in vivo studies. This effect was studied using a murine model that measured mortality and early cytokine responses after challenge with endotoxin. C57/BL6 mice weighing between 18 and 21 g were given a single intraperitoneal dose of lipopolysaccharide (LPS), ranging from 200 to 1000 microg. Mice were pre-treated with an intraperitoneal injection of 5% dextrose in sterile water containing 0.0-6.0 mg of ciprofloxacin 1 h before LPS challenge. Cytokine responses were assessed by measuring concentrations in serum separated from blood obtained by cardiac puncture of anaesthetized mice at 0, 1, 3, 6 and 24 h following LPS administration. Mice were observed for 72 h following administration of LPS and serum cytokines were measured using ELISA. More than 4.5 mg of ciprofloxacin (675-900 mg/m(2) or 225-300 mg/kg) given 1 h before LPS challenge consistently protected mice from a lethal dose of LPS (14/14 versus 0/7, P < 0.00001). Ciprofloxacin significantly attenuated the production of tumour necrosis factor-alpha and interleukin-12 response after LPS challenge. In addition, ciprofloxacin significantly increased serum interleukin-10 concentrations but had little or no effect on interleukin-6 or interleukin-1beta serum concentrations. Similar effects were evident with sublethal doses of LPS and were most pronounced at the lowest dose of LPS studied. These observations indicate that ciprofloxacin can prevent endotoxin-mediated death and alter early host cytokine responses. This effect may influence the course of infection in a manner that is independent of the drug's antimicrobial activity.     

Tumor necrosis factor-alpha is associated with early postresuscitation myocardial dysfunction

OBJECTIVE: Left ventricular dysfunction after successful cardiopulmonary resuscitation contributes to early death following resuscitation. The stress-induced proinflammatory cytokines, particularly tumor necrosis factor-alpha and interleukin-1beta, are known to depress myocardial function. We hypothesized that tumor necrosis factor-alpha and interleukin-1beta, synthesized and released in response to the stress of global ischemia accompanying cardiac arrest, play a role in development of postresuscitation left ventricular dysfunction. METHODS: Hemodynamic variables, tumor necrosis factor-alpha , interleukin-1beta, interleukin-6 (enzyme-linked immunosorbent assay method), and ionized calcium were measured in ten anesthetized swine before and after 7 mins of cardiac arrest and during the early postresuscitation period (60-90 mins). RESULTS: Tumor necrosis factor-alpha increased three-fold within 15 mins of restoration of circulation and remained elevated throughout the observation period. A significant negative correlation was observed between tumor necrosis factor-alpha and left ventricular systolic change in pressure over time (r = -.54, p <.001). Interleukin-1beta was undetectable before and after resuscitation, and interleukin-6 was detectable in only two animals after resuscitation. Although a significant decline in ionized calcium was observed and correlated with left ventricular systolic change in pressure over time, an independent role for ionized calcium in postresuscitation left ventricular dysfunction was not demonstrated. CONCLUSION: Tumor necrosis factor-alpha increases during the early postresuscitation period and may play a role in postresuscitation myocardial dysfunction.