The heat shock/oxidative stress connection

Involvement of free-radical oxidations in the aging process has been a topic of interest since Harman's original contribution. Because of the close association between aging and Alzheimer disease (AD) and the qualitative similarity in the neuropathology of both conditions, it has been proposed by many investigators that oxidative stress may be important in AD. If such modality of injury was indeed involved, one should expect to find markers of oxidation and heat shock (since free radicals are key mediators of heat-shock induction) in brains of patients with AD. In fact, several studies documented abnormal expression of antioxidant enzymes and heat-shock proteins (HSP) along with other markers of oxidation in AD brains. We showed that abnormally expressed antioxidant enzymes are topographically associated with senile plaques and neurofibrillary tangles, and that the activity of these enzymes is (contrary to what one would expect) markedly reduced. These findings have recently been confirmed by other investigators. Despite a large amount of evidence that suggests an association between oxidative stress and the pathogenesis of AD, it is not yet known whether oxidative stress is a cause or consequence of the disorder. Future research efforts regarding the oxidative stress hypothesis of AD should include attempts, at generating AD pathology by oxidative means in laboratory animals, determining the role and integrity of the heat-shock response in AD, as well as that of various antioxidant systems, growth factors, and hormones with antioxidant and neuroprotective properties.     

杀菌性通透性增强蛋白对失血性休克的保护作用及其机理

分别在失血和复苏开始即刻ｉｖ杀菌性／通透性增强蛋白（ＢＰＩ）１．５和３．５ｍｇｋｇ－１，观察ＢＰＩ对大鼠失血性休克转归的影响．结果显示，ＢＰＩ治疗能明显改善失血性休克大鼠肝肾功能，提高休克动物存活率（ＢＰＩ组８１％ｖｓ休克对照组４４％，Ｐ＜０．０５），ＢＰＩ组大鼠复苏后与休克前的血浆内毒素（０．２０±０．０４ｖｓ０．２４±０．０５ｋＵＬ－１）水平无明显变化，血浆肿瘤坏死因子α和白介素６水平较休克前明显升高，但均显著低于休克对照组．提示ＢＰＩ对失血性休克大鼠具有一定的保护作用，其机理可能与ＢＰＩ拮抗休克时内源性内毒素活性，抑制细胞因子反应有关．     

In vitro evaluation of ablation parameters of normal and fibrous aorta using smooth excimer laser coronary angioplasty

A modified exeimer laser energy delivery system was used to irradiate 100 segments of normal and fibrous aorta in vitro. The laser beam was scanned into 8 fiber bundles consisting of 50 fibers each resulting in a reduction of the applied pulse energy. The total repetition rate was increased to 150 Hz in order to keep the repetition rate per fiber bundle close to 20 Hz and to minimize thermal injury. The results demonstrate that effective ablation (etch rate per 8 pulses > 2.0 μm) occurred at an energy fluency of 50 mJ/mm² in both normal and fibrous aorta. Tissue damage (carbonization, tissue separation, fissures, cracks, and vacuolization) was in a range of 100 ± 28 to 152 ± 30 μm for normal aorta and in a range of 57 ± 35 to 110 ± 39 μm for fibrous aorta. We conclude that effective ablation of normal and fibrous human aorta can be achieved by the application of smooth excimer laser coronary angioplasty. This improvement of excimer laser technology may result in a reduction of shock wave- and cavitation-induced damage leading to a reduction of tissue injury. However, this awaits further in vitro and in vivo confirmation. © 1993 Wiley-Liss, Inc.     

抗氧化剂等药物联合应用治疗烧伤休克的实验研究

我们用哈白兔以3％凝固气油致25％Ⅲ°烧伤休克持续了3h复苏的动物模型研究了丹参、维生素E、抗氧化剂协同治疗烧伤休克的作用,效果显著。第5天SOD活性和MDA值均达到伤前水平,提高了动物存活时间。各项生化指标和病理证实,该组实验动物脏器无明显病变,说明联合用药,不仅可以有效的清除氧自由基,还能拮抗脂质过氧化作用,对脏器有较好的保护作用。     

人食管癌组织中热休克蛋白70和糖调节蛋白94的表达

为探讨人食管癌组织中热休克蛋白 70 (HSP70 )和糖调节蛋白 94( grp94)的表达及意义 ,采用SABC法检测人食管癌组织HSP70和grp94的表达 ,镜下观察HSP70和 grp94在癌组织及癌旁组织中的表达特点。结果 :92 .6%( 5 0 /5 4)食管癌组织中存在HSP70的表达 ,癌细胞存在胞质、胞核表达强度及部位的差异 ;而 grp94的表达阳性率为70 .4% ( 3 8/5 4) ,以胞质表达为主 ,而癌旁组织表达较少。提示 :人食管癌组织存在HSP70和 grp94的表达异质性 ,呈现了胞质、胞核的表达差异 ,HSP70和 grp94在人食管癌组织的表达特点为以后肿瘤抗原肽肿瘤疫苗的提取和实验奠定了基础。     

失血性休克复苏及监测指标研究进展

创伤、失血性休克是一古老的临床研究课题。不仅在平时常见，更重要的是与战伤救治密切相关。尽管近10年来取得了一些进展，但复苏时机、复苏目标、液体种类的选择、复苏后继续生命支持以及监测技术等仍是临床以及研究人员面临的重大挑战。本文将就近年来有关上述问题的最新研究进展进行分析和讨论，以期提高对该复杂综合征的认识，为今后的研究提供帮助。     

内毒素休克大鼠核因子κB活化规律及其在生物蝶呤诱生中的作用

目的观察内毒素休克大鼠血浆及主要脏器核因子(NF)κB活化规律及其对生物蝶呤(BH4)和一氧化氮(NO)表达水平的影响,探讨内毒素休克时NF-κB信号通路对BH4诱生NO的分子调控机制及其与多器官功能损害的关系。方法将47只大鼠按表格随机法分为正常组(8只)、内毒素／脂多糖(LPS)组(24只,每观察时相点8只,均同时注射LPS制成休克模型)和拮抗组[15只,每观察时相点5只,均同时注射LPS并以吡咯烷二硫代氨基甲酸盐(PDTC)拮抗]。休克及拮抗组于注射LPS后2、6、12 h观察,并与正常组同法处死,无菌留取大鼠血标本及肝、肺、肾组织,测定组织中NF-κB活性和三磷酸鸟苷环水解酶Ⅰ(GTP-CHⅠ)和诱导型一氧化氮合酶(iNOS)mRNA表达水平、血浆和组织中的BH4含量及NO水平、肝脏和肾脏功能指标、肺组织髓过氧化物酶活性。结果与正常组(例如肺组织中NF-κB活性为26±6)比较,LPS组大鼠组织中NF-κB迅速活化(P<0．01),并于注射后2 h达峰值(肺组织中为291±44);LPS组各组织中GTP-CHⅠ和iNOS mRNA表达、BH4和NO水平也较正常组明显升高(P<0．05或0．01),至伤后12 h仍持续较高水平。此外,该组相应器官功能均受到不同程度的损害。应用PDTC的拮抗组大鼠各组织中NF-κB活性均较LPS组有所降低,GTP-CHⅠ、iNOS mRNA表达及BH4、NO水平显著受抑,肝、肺、肾功能明显改善。结论内毒素休克时机体内NF-κB通路高度活化,并对BH4／NO系统具有明显调节效应;可通过下调BH4介导的iNOS的过度活化抑制NF-κB信号途径,从而减轻组织炎性反应,对机体脏器功能起到保护作用。     

感染性休克患者的负液体平衡与预后的关系

目的探究感染性休克治疗的前3天患者的液体平衡状态与预后的关系。方法采用回顾性对照研究。查看1999年1月至2003年12月收入首都医科大学附属复兴医院ICU的感染性休克患者病例记录,入选病例必须严格符合感染性休克的诊断标准,且既往无肾功能不全病史。采集病例相关数据以及诊断后第1、2、3天的液体平衡值。比较不同组别患者的急性生理和慢性健康评分(APACHEⅡ)、继发器官衰竭评分(SOFA)、液体平衡和病死率等数据。对影响患者预后的独立危险因素进行Logistic回归分析,确定和描述感染性休克患者的预后与在前3天的液体复苏治疗中出现的负平衡((0mL)相关因素的关系。结果负液体平衡患者与未出现负液体平衡患者2组的病死率差异有统计学意义(52.4%vs87.5%,χ2=5.303,P=0.021)。通过对入组时患者年龄、APACHEⅡ评分、第1天和第3天SOFA评分和正负平衡等影响患者预后的独立危险因素Logistic回归分析,表明前3天的治疗中,若有1d出现负液体平衡即可成为影响患者预后的独立危险因素(P=0.035)。结论在感染性休克前3天的治疗中,若有1d出现液体平衡负值即可成为影响感染性休克患者预后的独立因素,对感染性休克的28d生存预后有较强的预测性。在前3天的治疗中出现液体平衡为负值((0mL)的感染性休克患者的生存率比液体平衡为正值的患者的28d生存率高。     

伍用TRH与ICI174,864对兔失血性休克心功能的影响

采用脑室给药方法研究了促甲状腺素释放激素（ＴＲＨ）与δ－阿片受体特异性拮抗剂ＩＣＩ１７４，８６４合用对失血性休克兔心功能指标的影响，旨在探讨ＴＲＨ与ＩＣＩ１７４，８６４是否可配伍用药治疗休克。ＴＲＨ、ＩＣＩ１７４，８６４两药单用剂量各为５０μｇ，合用剂量各２５μｇ。结果显示，两药半量合用改善失血性休克兔心血管功能作用不仅可达单药５０μｇ的效果，且较单用效果更佳。表明两药可配伍用药治疗失血性休克，且有一定的协同作用。