钙蛋白酶抑制剂calpeptin对大鼠局灶性脑缺血再灌注损伤的影响

目的 应用大脑中动脉闭塞(MCAO)模型,研究钙蛋白酶抑制剂calpeptin对大鼠局灶性脑缺血再灌注损伤的影响.方法 32只SD大鼠随机分为4组,每组8只.单纯缺血组(I组):大脑中动脉闭塞2h;calpeptin组(C组)大鼠在2h的大脑中动脉闭塞前30min经侧脑室注射calpeptin50μg;二甲基亚砜(DMSO)组(D组)大鼠在2h的大脑中动脉闭塞前30min经侧脑室注射DMSO 5μL;对照组(S组)不闭塞大脑中动脉,其余手术操作同其他组.各组大鼠在2h的缺血后均再灌注48h.分别在再灌注12、24、48h行神经功能学评分,在再灌注48h后应用TTC染色法测定脑梗死体积.结果 S组大鼠在再灌注后各时间点的神经功能学评分与术前相比无明显变化,手术后48h未发现梗死灶.C组大鼠各时间点的神经功能学评分及再灌注48h脑梗死体积均低于I组和D组(P＜0.05),而I组和D组之间无显著性差异(P＞0.05).结论 缺血前应用钙蛋白酶抑制剂可以显著减轻大鼠局灶性脑缺血再灌注损伤.     

缓激肽预处理对大鼠局灶性脑缺血的影响

目的研究缓激肽预处理对大鼠局灶性脑缺血/再灌注损伤的影响。方法线栓法制备大鼠大脑中动脉缺血/再灌注模型,在缺血前由颈外动脉泵入缓激肽,对照组给予等量生理盐水,缺血2 h再灌注24 h后,观察脑梗死体积、脑含水量、血脑屏障通透性及组织病理学的变化。结果缺血前15 m in给予缓激肽组与对照组相比,梗死体积减小、水肿程度减轻、血脑屏障通透性降低、相关脑区神经元损伤程度减轻。结论预先给予缓激肽可对脑缺血损伤起保护作用,这可能是通过保护脑血管、减少梗死体积来起作用的。     

缺血后处理对局灶性脑缺血再灌注大鼠Bcl-xl、Bax的影响

目的:观察缺血后处理对局灶性脑缺血再灌注大鼠Bcl-xl、Bax的影响.方法:线栓法建立大鼠大脑中动脉缺血再灌注模型,将成年雄性Wistar大鼠144只,随机分成三组:假手术组、对照组(脑缺血再灌注组)、缺血后处理组.假手术组只进行假手术;对熙组(脑缺血再灌注组)给予90min大脑中动脉缺血(MCAO);缺血后处理组在大脑中动脉缺血90min后,给予灌注30s缺血30s,反复3次.各组分别再灌注12h、24h、48h、72h后测定脑组织Bcl-xl、Bax的表达.结果:局灶性脑缺血后再灌注前给予后处理,缺血后处理组与缺血再灌注组相比,Bcl-xl蛋白的表达明显增加,而Bax蛋白的表达明显减少.结论:脑缺血后处理增加脑缺血再灌注后Bcl-xl蛋白的表达、减少Bax蛋白的表达,从而抑制缺血周围区的细胞凋亡.     

黄芪注射液对大鼠局灶性脑缺血再灌注后梗死体积的影响

目的：本研究主要探讨黄芪注射液对大鼠局灶性脑缺血再灌注后的梗死体积的影响。方法：采用线栓法制作大鼠局灶性脑缺血再灌注损伤模型,腹腔注射黄芪注射液,TTC染色计算脑梗死体积比。结果：缺血2h,3h用药后梗死体积比缺血再灌注组差异有统计学意义（P〈0.05）,缺血4h,5h用药后梗死体积比缺血再灌注组差异没统计学意义（P〉0.05）。结论：黄芪注射液可以减少时间窗以内的脑梗死体积,超过时间窗对脑梗死体积没有差异性。     

黄芪对脑缺血再灌注损伤c-fos/c-jun表达和细胞凋亡的影响

目的:探讨黄芪注射液对大鼠局灶性脑缺血再灌注损伤后的保护作用。方法:采用线栓法阻断大鼠一侧大脑中动脉(MCA)血流2h,再灌注24h制成局灶性脑缺血再灌注损伤模型。将30只Wistar雄性大鼠随机分成假手术组、缺血再灌注组、黄芪组3组。造模前1h时黄芪组给与黄芪200mg/kg腹腔注射。假手术组、缺血再灌注组给予等剂量生理盐水。再灌注24h后断头取脑、切片,进行HE染色、c-fos和c-jun免疫组化染色和细胞凋亡检测。结果:缺血2h再灌注24h后,黄芪组和缺血再灌注组大鼠缺血侧皮层可检测到凋亡细胞,黄芪组凋亡细胞数明显少于缺血再灌注组,假手术组未见凋亡细胞;黄芪组和缺血再灌注组大鼠缺血侧皮层c-fos/c-jun阳性细胞数均高于假手术组,与缺血再灌注组相比,黄芪组大鼠缺血侧皮层c-fos/c-jun表达降低。结论:黄芪可抑制缺血再灌注损伤后缺血侧皮质的细胞凋亡。     

白藜芦醇预处理对大鼠局灶性脑缺血/再灌注损伤的神经保护作用

目的探讨白藜芦醇(resveratrol,Res)预处理对大鼠局灶性脑缺血/再灌注损伤的神经保护作用。方法♂SD大鼠45只,随机分为假手术组(Sham)、缺血/再灌注组(I/R)和白藜芦醇预处理缺血/再灌注组(Res+I/R),每组15只。采用线栓法行大脑中动脉阻断前脑血90min,拔出栓线实现再灌注。Res+I/R组缺血前30min腹腔注射白藜芦醇(30mg·kg-1)。再灌注后24h,用2,3,5-氯化三苯基四氮唑(TTC)染色显示梗死范围;再灌注72h后利用Morris水迷宫检测脑缺血后大鼠空间学习记忆能力,用电生理学方法检测白藜芦醇对脑缺血大鼠突触可塑性的影响。结果白藜芦醇预处理可以明显缩小脑梗死体积并改善大鼠的行为学障碍(P<0.05),在Morris水迷宫实验中Res+I/R组大鼠逃避潜伏期明显短于I/R灌注组(p<0.05),高频刺激后,I/R组海马CA1区NMDA受体依赖性的长时程增强(LTP)诱导障碍(n=5),Res+I/R组海马CA1区可诱导稳定的LTP(n=5)。结论缺血前30min白藜芦醇预处理对局灶性脑缺血/再灌注损伤具有神经保护作用,可以缩小脑梗死体积,并对大鼠的学习与记忆能力具有改善作用。     

促红细胞生成素和血管紧张素受体拮抗剂对脑缺血再灌注后梗死体积和脑组织水肿的影响

目的研究促红细胞生成素(EPO)和血管紧张素受体拮抗剂(ARB)对脑缺血后的脑保护作用。方法采用健康的SD大鼠,线栓法阻断一侧大脑中动脉血流2 h,再灌注24 h,建立局灶性脑缺血再灌注损伤模型(MCAO),治疗组分别予缺血再灌注前后经腹腔注射EPO 3 000 IU/(kg·d),或缬沙坦40 mg/(kg·d),评价大鼠神经功能,测定其脑梗死体积占全脑体积的百分比、脑组织的含水量。结果与缺血再灌注组相比,EPD处理组可改善神经功能缺失,减少脑梗死体积,降低梗死组织含水量,且经EPD预处理,改善更明显,差异有统计学意义(P<0.05);与缺血再灌注组相比,ARB处理组可减少脑梗死体积,降低梗死组织含水量,差异有统计学意义(P<0.05)。结论 EPD和ARB可减少脑梗死体积,降低梗死组织含水量,EPD可明显改善神经功能缺失,经EPD和ARB预处理改善更为明显,具有良好的脑保护作用。     

三七皂甙Rb对实验性脑梗死大鼠全血碳氧血红蛋白的影响

目的研究三七皂甙Rb1对大鼠脑梗死后全血碳氧血红蛋白及梗死面积的影响。方法采用SD雄性大鼠,通过栓塞大脑中动脉并于1h后再灌注复制局灶性缺血再灌注损伤模型。通过生化检测、免疫组织化学染色等方法观察脑缺血再灌注损伤后全血碳氧血红蛋白(COHb)含量以及不同剂量的三七皂甙Rb1对COHb的含量等方面的影响。结果①脑缺血再灌注损伤后,模型组的全血碳氧血红蛋白含量显著高于假手术组(P<0.05),并在再灌注24h达到一个高峰。②给予中剂量三七皂甙Rb1(10mg/kg)与模型组相比可显著升高脑缺血再灌注损伤后全血碳氧血红蛋白含量(P<0.05)。结论大鼠脑缺血再灌注损伤后全血碳氧血红蛋白含量显著升高。三七皂甙Rb1通过增加COHb含量改善脑缺血再灌注后的脑损伤,并减小脑梗死的体积。本研究为今后对脑梗死的治疗和科研可能提供了一个崭新的思路。     

尼莫地平对大鼠脑缺血再灌注损伤疗效分析

目的探讨尼莫地平对大鼠缺血再灌注损伤的保护作用。方法采用结扎颈总动脉的方法制备缺血再灌注模型,对缺血前、再灌注48h后对大鼠进行神经功能评分和脑梗死体积,对正常组、缺血前注射尼莫地平组、未注射尼莫地平组及再灌注后注射尼莫地平组4组大鼠神经功能评分和脑梗死体积。结果与模型组组相比,缺血前及灌注后静脉滴注尼莫地平大鼠神经功能缺损明显减少,脑梗死体积明显减少(P<0.05)。结论尼莫地平治疗脑缺血再灌注损伤有疗效,对脑缺血大鼠有神经保护作用,而且在缺血前给药能减少大脑梗死的面积。     

天麻素对大鼠局灶性脑缺血损伤的保护作用研究

目的 探讨天麻素(Gastrodine,Gas)对大鼠局灶性脑缺血损伤的保护作用及机制.方法 线栓法制备大鼠大脑中动脉栓塞模型,缺血2h后再灌注.天麻素(5,10,20 mg/kg)再灌注同时腹腔给药,再灌注后24 h,测定大鼠神经功能缺失评分和脑梗死体积,伊文思蓝法观察血脑屏障破坏程度,Western blot检测梗死半暗带皮层组织炎症因子TNF-α、IL-1β和IL-6的蛋白表达.结果 天麻素(10,20 mg/kg)能改善大鼠脑缺血后神经功能缺失,减小脑梗死体积,降低血脑屏障的通透性.天麻素(20 mg/kg)对梗死半暗带皮层组织TNF-α表达的抑制率为24％,对IL-1β表达的抑制率为34％,对IL-6表达水平的抑制率为38％.结论 天麻素可降低血脑屏障的通透性,其通过减低炎症反应而对局灶性脑缺血损伤发挥保护作用.     

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.     

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.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.