炎性介质在重症急性胰腺炎发病过程中的变化及作用

目的探讨急性重症胰腺炎(SAP)时，白细胞介素1(IL-1)、白细胞介素6(IL-6)和肿瘤坏死因子(TNF)的变化及相互关系。方法用5％牛磺胆酸钠行胰胆管注射制备SAP大鼠模型，根据实验分为假手术组和sAP组。用放免法检测各组不同时期(4h、12h、24h)血中IL-1、IL-6和TNF-a的水平。结果与假手术组相比，SAP组血IL-1、IL-6和TNF-a水平明显增高，且随着时段延长而增高。结论SAP时血IL-1、IL-6和TNF-a水平明显增高并与胰腺损伤程度相一致。     

白介素-2在急性脑梗死中的动态变化及预后

目的:比较脑梗死后症状改善及死亡患者血清IL-2在急性期的动态变化其在脑梗死预后中的作用.方法:收集我院24 h内出现急性脑梗死症状的57例患者在0、24、48、72和144 h这5个时间点的血清,使用ELSA法对检测其IL-2水平.结果:与对照组相比,0(0.86,P＜0.01)和24 h(1.06,P＜0.01)这两个时间点在急性脑梗死患者IL-2水平显著升高.患者症状好转后(N=40)IL-2浓度在后面的时间点逐渐下降(48,72 h和144 h,0.33,P＜0.05),但最终死亡患者(N=17)的各时间点IL-2浓度无明显变化.结论:IL-2水平与急性脑梗死的预后具有很好的相关性,可以作为判断预后的一个很有价值的标志物.     

IGF-1通过P38MAPK信号下调急性脑梗死大鼠脑组织中凋亡蛋白的表达及其意义

目的:探讨IGF-1通过调控p38MAPK影响急性脑梗死大鼠脑组织细胞凋亡的机制.方法:利用Western-blot检测假手术组(sham),手术组术后24h(MCAO-24h),IGF-1治疗组(IGF-1)3组大鼠脑组织中IGF-1、p38、p-p38,Caspase3和Caspase9和蛋白表达水平.采用ELISA方法检测各组大鼠外周血中IL-1β、IL-6和TNF-α的分泌水平.结果:各组大鼠脑组织中IGF-1蛋白含量比较,MCAO-24h组(0.71 ±0.05)低于Sham组(1.01±0.20)(t=2.85,P＜0.05),IGF-1组(1.54±0.12)高于MCAO-24h组(t=7.19,P＜0.05);各组大鼠外周血中IL-1β、IL-6和TNF-α的分泌水平比较,MCAO-24h组(55.25±2.84) (222.02±12.77) (6.78±0.01)细胞因子分泌水平均高于Sham组(30.94±1.09) (128.16±5.92)(28.88±1.54)(t=13.82,11.55,4.25,P＜0.01;P＜0.05);IGF-1处理组(40.54±2.89(184.98±15.28) (33.39±0.91)细胞因子分泌水平低于MCAO-24h组(t=6.28,3.22,3.18,P＜0.01;P＜0.05);各组大鼠脑组织中p-P38/p38蛋白含量比较,MCAO-24h组(1.51±0.24)高于Sham组(1.03±0.06)(t=5.05,P＜0.05)和IGF-1组(0.90±0.20)(t=11.15,P＜0.01);各组大鼠脑组织中Caspase3蛋白含量比较,MCAO-24h组(1.61±0.06)高于Sham组(1.10±0.03)(t=7.18,P＜0.05)和IGF-1组(1.14±0.05)(t=4.27,P＜0.05);各组大鼠脑组织中Caspase9蛋白含量比较,MCAO-24h组(1.59±0.08)高于Sham组(1.14±0.06)(t=5.88,P＜0.05)和IGF-1组(1.27±0.05)(t=5.08,P＜0.05).结论:IGF-1是参与急性脑梗死发生后脑组织细胞凋亡重要因子.其作用机制是其调控p38丝裂原活化蛋白激酶(p38 MAPK)信号通路,阻断p38和p-P38的活化,进而抑制下游凋亡因子caspase-3和caspase-9活化,起到保护大鼠脑组织神经细胞的作用.     

不同剂量乌司他丁对感染性休克兔肺损伤的保护作用及其机制探讨

目的 观察内毒素(ET)致感染性休克兔血浆中肿瘤坏死因子-a(TNF-a)、白介素-6(IL-6)和肺组织核转录因子-κB(NF-κB)水平变化,研究不同剂量乌司他丁(UTI)对感染性休克兔肺损伤的保护作用及其机制.方法 将50只健康日本长耳大白兔随机分为ET致休克模型组(对照组),地塞米松(DXM)干预组(DXM组)及三种不同剂量UTI干预组(U1组、U2组、U3组3个亚组),每组10只.采用ET(2mg/kg)一次性静脉注射方法复制兔感染性休克模型,造模成功后对照组应用0.9%氯化钠溶液2ml,DXM组用DXM(1mg/kg)、U1组用UTI(2.5×104)U/kg、U2组用UTI(5.0×104)U/kg、U3组用UTI(10.0×104)U/kg分别溶于2ml 0.9%氯化钠溶液静脉注射进行干预,监测兔的平均动脉血压(MAP)和呼吸频率(RR)的变化,检测休克0h和干预后2h、4h、6h和12h等时间点血浆中的TNF-a、IL-6水平,HE染色观察肺组织病理形态学变化,免疫组化染色检测肺组织NF-κB的表达.结果 在0h,5组兔的MAP、RR及TNF-a、IL-6水平差异无统计学意义(P＞0.05);3个UTI亚组与对照组及DXM组在休克后不同干预时间点MAP、RR及TNF-a、IL-6水平比较,差异均有统计学意义(P＜0.05);肺组织病理变化在对照组肺损伤最强,U3组最轻,差异有统计学意义(P＜0.05);NF-κB在肺组织的表达在对照组最强,U3组最轻,差异有统计学意义(P＜0.05).MAP、RR及TNF-a、IL-6的水平和NF-κB表达在3个UTI亚组间随着UTI剂量的加大,差异均有统计学意义(P＜0.05).结论 UTI能改善ET所诱导的感染性休克兔的MAP、RR和 TNF-a、IL-6的变化,尤以大剂量改善效果更明显.UTI对ET所诱导的感染性休克兔肺损伤有明显的保护作用,且UTI的肺保护作用与剂量成正相关性.通过抑制NF-κB信号转导通路抑制TNF-a和IL-6的表达是UTI肺保护作用的重要机制之一.     

脑出血大鼠血清IL-17,IL-23的表达及意义

目的:以脑出血大鼠为研究对象,探讨血清IL-17,IL-23的表达及意义.方法:将90只大鼠随机分成3组:对照组(A组),假手术组(B组),出血组(C组),每组30只.分别设6h,24h,3d,7d,14d五个时间点.用酶联免疫吸附法(ELISA)检测大鼠血清中白细胞介素17(IL-17)、白细胞介素23(IL-23)的表达.结果:对照组与假手术组IL-17,IL-23的表达在各时间点均无统计学差异(P＞0.05).出血组与对照组、假手术组相比、同一时间点IL-17,IL-23的表达均具有统计学差异(P＜0.05).出血组内各时间点IL-17,IL-23的表达相比,均具有统计学差异(P＜0.05).IL-17,IL-23的表达在脑出血后7d高于出血其他时间点,具有统计学差异(P＜0.05).结论:脑出血大鼠发病6h后,外周血中IL-17,IL-23的表达增加;IL-17,IL-23的表达在脑出血后7d高于6h,24h,3d,14d.IL-17,IL-23参与脑出血后的炎症反应.     

麻醉和术后镇痛对食管癌患者辅助性T淋巴细胞细胞因子的影响

目的 研究不同麻醉和镇痛方法对食管癌患者围术期Th1、Th2类细胞因子的影响.方法 择期食管癌开胸手术患者60例,随机均分三组.采用静脉麻醉,Ⅰ、Ⅱ组复合胸段硬膜外麻醉.术后Ⅰ、Ⅲ组行自控静脉镇痛,Ⅱ组行自控硬膜外镇痛.检测麻醉前(TO)、切皮后2h(T1)、术后4、24、48 h(T2、T3、T4)血清白细胞介素2(IL-2)、γ干扰素(IFN-γ)、肿瘤坏死因子a(TNF-a)和IL-4、H,6、IL-10浓度.结果 与T0比较,T2时Ⅰ组、Ⅲ组血清IL-10明显升高(P＜0.05),T2、T3时Ⅲ组血清IL-6水平明显升高,且明显高于Ⅰ组、Ⅱ组(P＜0.05).Ⅰ组T4血清Ⅱ,4水平明显高于T2(P＜0.05).结论 静脉麻醉复合胸段硬膜外阻滞和术后镇痛可减轻食管癌手术患者的细胞免疫抑制.     

CD

目的研究褪黑素治疗应激性溃疡大鼠时CD4+T细胞和白介素-2(IL-2)的表达.方法100只雄性SD大鼠按体重随机分成5组正常对照组、预防对照组、褪黑素预防低、高剂量组和褪黑素治疗组,各组均20只.采用水浸-束缚(WIR)应激实验复制大鼠应激性溃疡模型.应激前30 min预防对照组、褪黑素预防低、高剂量组分别腹腔注射等体积的含1%二甲基亚砜的生理氯化钠溶液、褪黑素5和20 mg·kg-1,褪黑素治疗组则于应激后1 h腹腔注射褪黑素20 mg·kg-1.应激6 h后观察各组大鼠胃黏膜病变情况,对溃疡指数(UI)进行评分,同时检测各组大鼠超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和IL-2水平及CD4+T比例.结果预防对照组大鼠SOD和GSH较正常对照组明显降低(P＜0.01),褪黑素预防组(5或20 mg·kg-1)和治疗组的SOD和GSH均较预防对照组明显升高,且褪黑素治疗组的IL-2水平和CD4+T比例较预防对照组显著升高(P＜0.001).褪黑素预防组(5或20 mg·lg-1)和治疗组的UI均显著低于预防对照组,且20 mg·kg-1预防组低于5 mg·kg-1预防组(P＜0.05).结论褪黑素可通过增高SOD和GSH水平,并激活CD4+ T细胞,促进IL-2的分泌,从而发挥对应激大鼠的抗氧化抗凋亡作用.     

长托宁对冠状动脉搭桥术心肺转流期间炎性细胞因子的影响

目的 观察长托宁对冠状动脉脉搭桥术(CABG)心肺转流(CPB)炎性细胞因子的影响.方法 39例接受CABG手术的患者完全随机分为长托宁1组、长托宁2组和对照组,各13例.长托宁1组和长托宁2组术前30 min肌内注射长托宁0.02～0.03 mg/kg;长托宁2组术后第24、48小时各静脉追加一次长托宁0.02～0.03 mg/kg;对照组术前30 min肌内注射阿托品0.01 mg/kg.观察3组患者注药前及注药30 min后体温及心率,分别于麻醉诱导前、CPB开始30 min、术后即刻、术后24、48 h采动脉血检测肿瘤坏死因子a(TNF-ct)、白细胞介素6(IL-6)和IL-8的浓度;观察术后胸部X线片肺炎发生率、呼吸机支持时间及ICU停留时间.结果 注药30 min后对照组患者的心率较注药前明显升高[(78.2±3.4) 次/min比(61.1±3.2)次/min;P＜0.05],且明显高于长托宁1组和长托宁2组同时间心率[分别为(56.7±1.4)、(58.9±5.3)次/min,均P＜0.05];与麻醉诱导前相比,CPB后对照组炎性细胞因子的浓度均明显升高,CPB结束时达到最高值,术后缓慢下降,术后24、48 h均高于术前[TNF-a(12.2±2.1)ng/L比(19.4±1.7)ng/L、(26.3±2.5) ng/L、(19.1±1.7)ng/L、(16.3±1.3)ng/L,P＜0.05].组间比较,长托宁1组和长托宁2组最高值明显低于对照组(P＜0.05);长托宁2组术后第24、48小时TNF-a、IL-6、IL-8值明显低于对照组,长托宁1组和长托宁2组术后呼吸机支持时间和ICU停留时间明显少于对照组[(10.6±3.7)h、(9.6±7.7)h,(11.8±7.7)h,(3.5±1.9)h、(3.0±1.8)h比(3.9±1.8)h,均P＜0.05].结论 CABG患者术前及术后应用长托宁能有效抑制炎症细胞因子TNF-a、IL-6、IL-8的释放,减轻CPB后的肺部炎症,缩短机械通气和ICU停留时间,比单纯术前应用长托宁效果更好.     

重组脂联素腺相关病毒载体对大鼠滑膜细胞TNF-a、IL-6和BAFF mRNA表达的影响

目的 研究重组脂联素(AD)腺相关病毒载体对大鼠滑膜成纤维细胞(SFLs)肿瘤坏死因子a(TNF-a)、白细胞介素6(IL-6)和B细胞激活因子(BAFF)mRNA表达的影响.方法 采用胶原酶消化法制备大鼠SFLs.携带AD基因的腺相关病毒按不同转染复数(MOI)转染大鼠SFLs,于第7天采用RT-PCR方法检测细胞因子AD、TNF-a、IL-6、BAFF mRNA表达.结果 成功培养出大鼠SFLs,转染后的SFLs AD mRNA表达随MOI升高而增加;在MOI=5×10<'5> v.g./cell时,TNF-a、IL-6、BAFF mRNA表达最高.结论 大鼠SFLs中高表达AD能够促进TNF-a、IL-6和BAFFmRNA表达,提示AD参与炎性反应和B细胞活化,在类风湿关节炎的慢性炎症过程中发挥重要作用.     

氟比洛芬酯超前镇痛对颅脑手术患者细胞因子水平的影响

目的:研究氟比洛芬酯对颅脑手术患者超前镇痛效果及对围术期血清炎性细胞因子水平的影响.方法:选择神经外科手术患者40例,ASA Ⅰ～Ⅱ级,随机分为C组和F组,每组20例.采用双盲法分别于气管插管后(切皮前15min)静脉注射氟比洛芬酯10mL(F组)或安慰剂(C组)10mL.记录术后2、24、48 h的镇痛评分(VAS值).在麻醉开始前(T1)、手术2 h(T2)、术毕(T3)及术后24 h(T4)测血清肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6和IL-10含量.记录麻醉时间、术中出血量、尿量和手术输液量及瑞芬太尼和丙泊酚用量.结果:(1)术后2 h和24 h的VAS评分F组均较C组明显减低(P＜0.05).(2)F组瑞芬太尼和丙泊酚用量较C组明显降低(P＜0.05).(3)与T1比较,2组T2、T3时点血清TNF-α含量均明显升高(P＜0.05),且在T2时点达高峰;与C组比较,F组T2～T4时点血清TNF-α含量明显降低(P＜0.05).与T1比较,2组T2～T4时点血清IL-6、IL-10含量均明显升高(P＜0.05),且在T3时点达高峰;与C组比较,F组T2～T4时点血清IL-6含量降低、IL-10含量升高(P＜0.05).结论:术前预给氟比洛芬酯注射液具有确切的超前镇痛作用,并能降低颅脑手术围手术期应激炎性反应.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.