Effects of hydroxyethyl rutosides upon the permeability of single capillaries in the frog mesentery.

1. We have investigated the effects of a standardised mixture of hydroxyethyl rutosides (HR) upon the permeability of the walls of single capillaries and venules of the frog mesentery. 2. In each experiment a single vessel was perfused via a micropipette with frog Ringer solutions containing bovine serum albumin (10 mg ml-1) and Ficoll 70 (40 mg ml-1) first in the absence of HR and then with HR added to the perfusate. The permeability of the vessel walls was assessed during each perfusion by using a development of the Landis micro-occlusion technique to estimate their hydraulic permeability (Lp) and the effective osmotic pressure (sigma delta pi) exerted across them by the perfusate macromolecules. 3. Measurements were made both in vessels which appeared to be healthy and in vessels showing signs of stasis or inflammation before perfusion. 4. HR at concentrations of 1.0, 0.1 and 0.01 mg ml-1 reduced hydraulic permeability to approximately half of its value in the absence of HR. It increased sigma delta pi to macromolecules at concentrations of 10, 1.0, 0.1, 0.01 and 0.001 mg ml-1. The effects of HR upon permeability were not reversed within 10 min of perfusion with an HR-free solution. 5. Ultrastructural examination of a number of vessels in which initial high values of permeability were reduced to values within the normal range of permeabilities by HR, showed clear signs of damage to the endothelium, with large gaps between adjacent endothelial cells. 6. These observations suggest that HR does reduce microvascular permeability both in healthy vessels and vessels showing of inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of hydroxyethyl rutosides and related compounds on lipid peroxidation and free radical scavenging activity. Some structural aspects.

Four hydroxyethyl rutosides, 7,3',4'-trihydroxyethyl quercetin, quercetin and a commercial standardized mixture of hydroxyethyl rutosides were investigated on non-enzymatic lipid peroxidation, for hydroxyl radical scavenging activity and interaction with 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH). It was found that the tested compounds exhibited a considerable inhibition of microsomal lipid peroxidation. They were less active than the reference compound quercetin, and this was attributed to their structural characteristics. They were also found to be potent hydroxyl radical scavengers and to interact with DPPH. As hydroxyl radical scavengers, they were more potent than the scavengers mannitol and dimethyl sulphoxide. These properties could be considered as a useful and exploitable combination.     

Protective action of propionyl-L-carnitine on toxicity induced by hyperbaric oxygen

The protective effect of propionyl-L-carnitine against hyperbaric oxygen toxicity was studied by in vivo experiments on mice. The treatment reduced both the percentage of animals with convulsions and the death rate. Tissue signs of toxicity and pulmonary weight increase were less marked in treated animals than in controls. Results may indicate that propionyl-L-carnitine needs to build up to critical levels in cells and mitochondria before its metabolic effects can be fully felt.     

Protective action of 9-hydroxypinoresinol against oxidative damage in brain of mice challenged with kainic acid

The neuroprotective effect of 9-hydroxypinoresinol was examined in mice challenged with kainic acid (KA), a potent central nervous system excitotoxin. For this purpose, mice were administered intraperitoneally with 9-hydroxypinoresinol before KA injection. A remarkable neuroprotective effect was observed with a single dose of 9-hydroxypinoresinol (30 mg kg(-1)) 24 h before KA challenge. Furthermore, 9-hydroxypinoresinol (20 mg kg(-1)) administered for 3 days before KA challenge reduced the mortality (60%) induced by KA to zero, and alleviated behavioural signs of KA neurotoxicity. Additionally, pretreatment with 9-hydroxypinoresinol (20 mg kg(-1)) prevented the decrease in the levels of total glutathione (GSH) and thiobarbituric acid reactive substances (P < 0.05). GSH peroxidase activity in brain tissue was restored to control levels, although GSH reductase activity and GSH S-transferase activity were not affected. Such a protective action was also observed even with a lower dose (10 mg kg(-1)) of 9-hydroxypinoresinol administered for 3 days, albeit to a lesser extent. From the results, it is proposed that 9-hydroxypinoresinol exerts a potent neuroprotective effect mainly by preventing oxidative stress in brain tissue of mice challenged with KA.     

Reaction of indomethacin with singlet molecular oxygen

Singlet molecular oxygen is a highly reactive species and is capable of disrupting cell membranes and collagen. It may also play a role in the synthesis of prostaglandins. We show here that indomethacin can react with singlet molecular oxygen and suggest that part of the anti-inflammatory action of this drug may stem from its ability to scavenge singlet oxygen.     

膜修饰脂质体对缺氧心肌细胞的保护作用

目的考察亲脂性化合物3{4[2羟基(1甲基乙胺基)丙氧基]苯基}丙酸十六醇酯(PAC)膜修饰脂质体对缺氧心肌细胞的保护作用。方法将普通脂质体(Plain L)、PAC膜修饰脂质体(PAC L)分别于常氧和缺氧条件下与乳鼠心肌细胞共同培养1、22、4 h,荧光法测定正常与缺氧心肌细胞对脂质体的摄取,以不加脂质体的细胞为对照,台盼兰染色法测定心肌细胞存活率。结果在常氧状态下1、2、24 h心肌细胞对PAC L的摄取较Plain L分别高约3.97、3.87、4.27倍,而在缺氧状态下心肌细胞对PAC-L的摄取较Plain L分别高约4.26、6.24、29.51倍。当细胞连续缺氧24 h时,对照组、Plain L组、PAC L组的心肌细胞存活率分别为7.8%、29.7%、95.4%。结论与Plain L相比,PAC L对缺氧状态的心肌细胞具有较强的亲和性,脂质体的加入能够明显降低缺氧对心肌细胞的损伤,PAC L对缺氧心肌细胞具有较强的保护作用,效果明显优于Plain L,且随着缺氧时间的延长这种优势越显著。     

青蒿琥酯对热灭活大肠杆菌攻击小鼠的保护作用

目的：观察青蒿琥酯（Artesunate，AS）对热灭活大肠杆菌攻击小鼠的保护作用以及对热灭活大肠杆菌诱导小鼠腹腔巨噬细胞释放TNF-α和IL-6的影响.方法：采用尾静脉注射LD90剂量的热灭活大肠杆菌攻击小鼠，于注射热灭活大肠杆菌后0、4、24、48h重复肌肉注射AS，观察给药后7d内小鼠的死亡率；体外培养小鼠腹腔巨噬细胞，培养体系中预先加入不同浓度AS 2h后，观察AS对热灭活大肠杆菌诱导小鼠腹腔巨噬细胞释放TNF-α和IL-6情况。结果：AS可明显推迟热灭活大肠杆菌攻击小鼠的死亡时间，并降低小鼠死亡率，死亡率由100％降低至50％（P〈0．05）。预先加入的AS能明显抑制热灭活大肠杆菌诱导的小鼠腹腔巨噬细胞释放TNF-α和IL-6，并呈明显量效关系。MTT实验结果显示24h内AS对细胞活力无影响。结论：AS对热灭活大肠杆菌攻击小鼠具有显著保护作用，该保护作用可能与其明显抑制促炎细胞因子释放有关。     

蕨麻醇提物对心肌细胞缺氧损伤的保护作用*

目的:探讨蕨麻(Potentilla anserina L．)对心肌细胞缺氧损伤的保护作用。方法:采用原代培养的SD乳鼠心肌细胞建立缺氧损伤实验模型,通过MTT法测定各组细胞代谢率,生化方法测定乳酸脱氢酶(LDH)和肌酸激酶(CK)的释放量以及细胞内超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果:蕨麻醇提物在24,12和6g·L~(-1)浓度能显著减少缺氧损伤心肌细胞LDH和CK的外漏量,并可显著提高细胞内SOD活性,减少MDA的产生。结论:蕨麻对心肌细胞缺氧损伤具有显著的保护作用,其机制之一可能是清除缺氧导致的心肌细胞自由基堆积,减少脂质过氧化。     

荭草苷对缺氧-复氧心肌细胞的保护作用

目的探讨荭草苷 (orientin)对缺氧 复氧损伤心肌细胞的保护作用及其机制。方法采用原代培养的新生大鼠心肌细胞建立缺氧 复氧损伤模型 ,实验分为正常细胞培养组、缺氧 复氧损伤模型组、缺氧 复氧损伤 +荭草苷 (3、10、30 μmol·L-1)组、缺氧 复氧损伤 +verapamil(5 μmol·L-1)组。用黄嘌呤氧化酶法测定SOD的活力 ,硫代巴比妥酸显色法测定MDA含量 ,MTT染色法测定线粒体脱氢酶活性改变并测定LDH含量变化 ,荧光法测定细胞内钙浓度的变化。结果荭草苷可显著提高缺氧 复氧损伤心肌细胞内SOD的活性及细胞内线粒体脱氢酶活性 ,并能显著抑制LDH的活性、MDA的生成以及细胞内钙浓度。结论荭草苷具有明显的抗缺氧 复氧损伤 ,保护心肌细胞的作用     

羟乙基淀粉对急性心肌缺血保护作用的实验研究

目的研究羟乙基淀粉(万汶)对急性心肌缺血的保护作用。方法制作SD大鼠急性心肌缺血损伤模型,随机分为假手术组、扎闭冠状动脉组、羟乙基淀粉干预组。假手术组开胸进行冠状动脉左前降支穿线而不予结扎,其余各组均结扎冠状动脉左前降支,并计时。羟乙基淀粉干预组在冠状动脉左前降支结扎前30 min经尾静脉给予羟乙基淀粉5 mL/kg,其余各组输注等量生理盐水。在扎闭冠状动脉6 h后处死动物,取心肌组织进行免疫组织化学和流式细胞术检测NF-κB活性。结果NF-κB的表达和激活在扎闭冠状动脉后较对照组明显增多(P<0.05),羟乙基淀粉可以明显降低缺血后心肌组织NF-κB的表达和激活。结论单纯心肌缺血可以激活心肌组织NF-κB,NF-κB可能参与了心肌缺血病理的发生、发展,羟乙基淀粉可能通过降低NF-κB的表达活化而参与心肌保护作用。     

Effects of edaravone on singlet oxygen released from activated human neutrophils

The effects of edaravone, a curative agent for acute brain infarction, on singlet oxygen ((1)O2) released from activated human neutrophils were examined, and the effects were compared to those of histidine, a (1)O2 singlet oxygen scavenger. The neutrophils, stimulated with opsonized zymosan, released (1)O2 that was detected by chemiluminescence using a (1)O2 specific probe, trans-1-(2'-methoxyvinyl)pyrene. Edaravone dose-dependently suppressed the (1)O2 release with an IC(50) of approximately 0.3 microM, while the IC(50) of histidine was approximately 1 mM. This (1)O2 scavenging activity of edaravone might be involved in its curative effects on acute brain infarction.     

青蒿素对CpG DNA攻击小鼠保护作用的实验研究

目的:观察青蒿素对CpGDNA攻击小鼠的保护作用及对CpGDNA诱导小鼠单核 巨噬细胞RAW2 6 4.7释放促炎细胞因子的影响。方法:清洁级昆明小鼠6 0只,随机分为CpGDNA、青蒿素(2 0 0mg·kg-1)、CpGDNA 青蒿素(5 0、10 0、2 0 0mg·kg-1)及生理盐水对照组,每组动物10只。CpGDNA及CpGDNA 青蒿素组小鼠提前1h腹腔注射D 氨基半乳糖溶液(6 0 0mg·kg-1)进行敏化。CpGDNA组尾静脉给予4mg·kg-1的CpGDNA敏化;青蒿素组,灌胃给予2 0 0mg·kg-1的青蒿素;CpGDNA 青蒿素组在给予不同剂量的青蒿素后,立即给予4 0mg·kg-1的CpGDNA敏化;生理盐水对照组仅给予相同量的生理盐水。体外培养小鼠巨噬细胞RAW2 6 4.7,加入不同浓度的青蒿素,观察其对CpGDNA刺激细胞分泌TNF α及IL 6的拮抗作用及其量效、时效关系。结果:青蒿素可降低CpGDNA引起的小鼠死亡,死亡率由80 %降至10 % (P <0 .0 1)。青蒿素在2 0g·ml-1时显著抑制CpGDNA诱导RAW2 6 4.7释放TNF α和IL 6 (P <0 .0 1)。提前给予青蒿素,其拮抗CpGDNA诱导细胞因子释放的作用非常显著(P <0 .0 1) ,但青蒿素在刺激物CpGDNA给予后再加入,也能观察到显著拮抗作用(P <0 .0 5 )。结论:青蒿素对CpGDNA攻击小鼠具有显著保护作用,该保护作用可能与其明显抑制CpGDNA诱导的促炎细胞因子释放     

极化心脏停搏液对离体成熟心肌细胞保护作用的研究

目的观察Na+通道阻滞剂河豚毒素(TTX)极化心脏停搏液对离体成熟大鼠心肌细胞内[Ca2+]i的影响,探讨其对成熟心肌细胞的保护作用。方法成年Wistar大鼠心脏,用酶解法分离成具有搏动性的单个成熟心室肌细胞悬液,随机分成基础组、STH2组和TTX组,STH2组和TTX组分别应用St.ThomasⅡ号停搏液和TTX停搏液处理,建立模拟缺血/再灌注损伤的停搏/复搏细胞模型,采用激光扫描共聚焦显微镜(LSCM)测定各组细胞不同时期的[Ca2+]i。结果 TTX组和STH2组成熟心肌细胞复搏后[Ca2+]i均明显高于基础组,TTX组明显低于STH2组,差异均有统计学意义(P<0.01)。结论极化心脏停搏液较去极化心脏停搏液能减轻成熟心肌细胞Ca2+超载,对离体成熟心肌细胞有较好的保护作用。     

异丙酚对第三丁基过氧化氢诱导的心肌细胞凋亡的保护作用

目的观察异丙酚对第三丁基过氧化氢(t-BHP)诱导的心肌细胞凋亡的影响并探讨可能的机制。方法采用SD新生大鼠进行心肌细胞原代培养。实验分为5组:正常对照组、t-BHP组和异丙酚1、10、30μmol.L-1组。分光光度计法检测细胞内谷胱甘肽(GSH)、丙二醛(MDA)水平和超氧化物岐化酶(SOD)活性;四甲基偶氮唑盐比色法(MTT)检测细胞线粒体活性,罗丹明123(Rhodamine123)荧光染色、流式细胞仪检测细胞线粒体膜电位(ΔΨm),流式细胞术(FCM)测定细胞凋亡率,Western blot法检测caspase-3的表达。结果与正常对照组相比,100μmol.L-1的t-BHP处理心肌细胞4 h后,细胞内GSH水平明显下降(P<0.05),MDA含量增加(P<0.01),抗氧化酶SOD活性降低(P<0.01),细胞线粒体活性降低(P<0.01),线粒体膜电位ΔΨm明显下降(P<0.01),细胞凋亡率和caspase-3的表达明显升高(P<0.01);异丙酚10、30μmol.L-1能减少过氧化氢所致的细胞中MDA含量升高;提高SOD活性和GSH水平;提高线粒体活性、膜电位;抑制心肌细胞凋亡和caspase-3的表达升高(P(0.05,P(0.01)。结论异丙酚能减弱过氧化氢所致的心肌细胞凋亡,其作用机制可能是通过减少活性氧自由基导致的细胞膜氧化损伤、提高线粒体活性、维持线粒体的膜电位,从而抑制心肌细胞凋亡的发生。     

极化心脏停搏液对离体成熟心肌细胞保护作用的研究

目的 观察Na+通道阻滞剂河豚毒素(TTX)极化心脏停搏液对离体成熟大鼠心肌细胞内[Ca2+]I的影响,探讨其对成熟心肌细胞的保护作用.方法 成年Wistar大鼠心脏,用酶解法分离成具有搏动性的单个成熟心室肌细胞悬液,随机分成基础组、STH2组和TTX组,STH2组和TTX组分别应用St.Thomas Ⅱ号停搏液和TTX停搏液处理,建立模拟缺血/再灌注损伤的停搏/复搏细胞模型,采用激光扫描共聚焦显微镜(LSCM)测定各组细胞不同时期的[Ca2+]I.结果 TTX组和STH2组成熟心肌细胞复搏后[Ca2+]I均明显高于基础组,TTX组明显低于STH2组,差异均有统计学意义(P<0.01).结论 极化心脏停搏液较去极化心脏停搏液能减轻成熟心肌细胞Ca2+超载,对离体成熟心肌细胞有较好的保护作用.     

Protective action of timolol in acute myocardial ischemia.

Timolol, a beta-adrenoceptor blocking agent with little or no cardiodepressant activity, was studied in acute myocardial ischemia in cats. Timolol, at a dose of 25 mug/kg, blocked 75 to 80% of the cardiac response to isoproterenol. This dose also significantly reduced heart rate in cats subjected to acute myocardial ischemia by ligation of the left coronary artery. Timolol significantly prevented the spread of ischemic damage in the myocardium as assessed by (a) curtailing the increase in plasma creatine phosphokinase (CPK) activity, (b) preventing the loss of CPK from the ischemic portion of the myocardium, and (c) restoring the elevated S-T segment of the electrocardiogram toward normal. Timolol did not significantly retard the increase in fragility of lysosomes in ischemic myocardial tissue. The mechanism of the protective effect to timolol on the ischemic myocardium appears to be via reducing myocardial oxygen demand by decreasing heart rate.     

Reactions of antiphlogistic indole derivatives with singlet oxygen. 1. Participation of reactive oxygen species in the mechanism of prostaglandin synthesis

Reactions of Antiinflammatory Indole Derivatives with Singlet Oxygen, I: Participation of Reactive Oxygen Species in the Mechanism of Prostaglandin Synthesis The reactions of singlet oxygen with antiinflammatory indole derivatives, such as indomethacin (1a) and acemethacin (1b) , which inhibit prostaglandin synthesis, are described, The reactions are fast and the products isolated are similar to those from reactions of other indole derivatives with singlet oxygen. The initial step is a (2+2)-cycloaddition of ¹O₂ as electrophilic agent onto the indole to form a dioxetane 2. This intermediate can react by ring opening to yield the o-acylanilides 4a - d and the substituted ester 4e . Recyclisation leads to the benzoxazinone 5 . Also the lactone 7 was isolated. The products 4a - e , 5 and 7 were identified by spectroscopic methods. These reactions may be relevant for the mechanism of prostaglandin synthesis, if ¹O₂, is the reactive species.     

Kappa－硒化卡拉胶对阿霉素毒性的预防作用

Ｋａｐｐａ－硒化卡拉胶给大鼠ｉｇ５．１５．４５ｍｇ·ｋｇ－１．ｇｄ．共１４次．在１５．４５ｍｇ·ｋｇ－１剂量组能显著提高注射阿霉素（ｉＰ３ｍｇ·ｋｇ－１，隔日１次．共４次）之大鼠全血谷胱甘肽过氧化物酶活性（Ｐ＜０．０５）．在３个剂量组不同程度改善心电图变化。对阿霉素引起的白细胞、血小板的减少也有抑制（Ｐ＜０．０５或Ｐ＜０．０１）．大剂量卡拉胶组．还可改善阿霉素所致心脏与肝脏的形态改变。Ｐ＜０．０１表３各组大鼠血小板计数值（×１０９·Ｌ－１，）各组均与阿霉素组比较．＊Ｐ＜０．０５，Ｐ＜０．０１＊Ｐ＜０．００１２．２，４对心及肝脏病理切片形态观察给药结束后第５周处死动物，取心、肝脏以３．３×１０３μｍｏｌ·Ｌ－１福尔马林固定，石蜡切片（５μｍ厚），ＨＥ染色，光镜检查。结果表明，阿霉素对心脏有明显的毒性作用，表现为心肌明显的空泡变，灶性肌溶解，而加亚硒酸钠和Ｋａｐｐａ－硒化卡拉胶，其变性程度及范围有改善，表现为肌细胞空泡变性及肌溶解的数量有较明显的减少。阿霉素对肝脏的毒性作用，表现为肝细胞明显的空泡变性及少量的点状坏死，如用硒化卡拉胶或亚硒酸钠肝细胞变性范围程度有不同改善，表现为空泡变性范围缩小，点状坏死减少，尤?