D-聚甘酯注射液对大鼠局灶性脑缺血再灌注损伤的保护作用

目的观察D-聚甘酯注射液对大鼠局灶性脑缺血再灌注损伤的保护作用。方法将雄性Wistar大鼠随机分为假手术组、模型组、D-聚甘酯注射液组等,采用改良的Longa法,建立大鼠局灶性脑缺血再灌注(IR)损伤模型(MCAO),各给药组在造模后连续给药7 d,对大鼠神经功能缺损进行评分,测定脑梗塞面积、脑含水量、脑组织HE染色。结果 (1)D-聚甘酯给药组在IR 144 h与模型组相比,评分差异显著(P<0.05)。(2)D-聚甘酯可明显降低脑梗塞面积,与模型组相比有显著性差异(P<0.05)。(3)脑含水量,给药组与模型组相比无显著性差异。(4)HE染色后,模型组神经细胞损害及间质水肿渐进性加重。D-聚甘酯可明显减轻神经细胞损害。结论 D-聚甘酯注射液对局灶性脑缺血再灌注大鼠具有保护作用。     

甘糖酯对实验性微循环障碍的保护作用

应用甘糖酯（ＰＧＭＳ）对实验性大鼠肠系膜微循环障碍的影响进行了观察，并通过流速，流态，存活率等指标评价ＰＧＭＳ的活性作用，结果提示ＰＧＭＳ能显著地改善了内脏微循环功能，减轻羊水造成的微循环损害。     

脑缺血再灌注损伤及脑保护药物研究进展

脑是一个对缺血缺氧最为敏感的器官,近年来,脑血管病的发病率逐年升高,在这一疾病发生发展过程中,缺血再灌注损伤（ischemia reperfusion injury）在脑血管病的发生发展中起着重要的作用。缺血再灌注致使神经元损伤的过程复杂,主要机制为线粒体受损、能量代谢异常、钙超载、兴奋性氨基酸（excitatory amino acids,EAAs）的神经毒性、自由基的积累、炎症相关介质产生等,致使细胞凋亡程序激活。通过对以上各机制的深入研究有助于明确各种脑保护药物的作用靶点。本文就脑缺血再灌注导致脑损伤的相关机制及最新治疗药物进展进行综述。     

降纤酶对大鼠脑缺血再灌注损伤保护作用的实验研究

目的探讨降纤酶对脑缺血再灌注损伤的保护作用及其作用机制。方法肾血管型高血压大鼠(RHR)70只 ,随机分为降纤酶组、对照组和伪手术组 ,按Longa氏方法改良复制成可再灌注的大脑中动脉闭塞 (MCAO)模型 ,缺血2h后恢复灌注。降纤酶组经股静脉给予降纤酶10U·kg-1体重 ,对照组给予等量的生理盐水。脑片行TTC及HE染色 ,观察两组在不同时间点的梗死灶的大小、脑微血管损害的表现及并发出血情况。结果降纤酶组的梗死灶的体积较对照组明显缩小 ,脑微血管损害减轻 ,镜下出血灶减少。结论降纤酶具有保护脑缺血再灌注损伤的作用。     

脑缺血及再灌注损伤保护性药物的研究进展

缺血性脑卒中发病率、病死率和致残率高,可引起生活质量的严重下降,给社会及家庭带来了沉重的经济负担,而临床上应用有效的药物却少之又少,为此缺血性脑卒中的保护性药物成为研究热点。本文主要综述了近几年临床前应用脑缺血及再灌注损伤保护药物的实验室结果,以期对临床试验及药物的研发提供线索,从而有助于提高脑卒中病人的存活率及生活质量。     

甘糖酯对肺心病患者抗氧化作用机制的探讨

慢性肺心病３６例，随机分为２组，甘糖酯组１８例在常规治疗基础上加用ＰＧＭＳ２００ｍｇ于５％葡萄糖氯化钠注射液５００ｍｌ中静滴，ｑｄ，共１０ｄ。并与常规治疗组１８例对照。结果：治疗后２组脂质过氧化物的均显著降低。谷胱甘肽过氧化物酶及过氧经氢酶均显著升高；经组间比较，ＬＰＯ的     

甘糖酯治疗高脂血症40例

对４０例高血脂患者（男２４例女１６例，年龄５７±９岁）口服甘糖酯１００ｍｇ，每日３次，疗程为２８天，并在治疗前及服药后１５天，２８天分别观察其血脂的变化。结果：治疗后１５天和２８天胆固醇，甘油三酯均明显降低（Ｐ〈０．０５～０．０１），治疗后２８天高密度脂蛋白胆固醇才明显升高（Ｐ〈０．０５），治疗过程中除１例口干外，未见严重副作用，我们认为甘糖酯治疗高脂血症安全，有效，值得临床推广使用。     

硫酸镁对大鼠局灶性脑缺血再灌注损伤的神经保护作用

急性脑缺血再灌注后神经损伤在临床上发生率高 ,病人预后差 ,目前尚缺乏确切有效的治疗手段。研究表明Ｎ 甲基 Ｄ 天门冬氨酸 (ＮＭＤＡ)受体介导的神经兴奋毒性在缺血性脑损伤中起关键性作用。硫酸镁是ＮＭＤＡ受体的非竞争性拮抗剂 ,本实验意在探讨其对大鼠脑缺血再灌注后神经损伤的保护作用 ,为临床应用硫酸镁防治脑缺血损伤提供实验依据。方法和结果方法 :选 50只ＳＤ大鼠 ,参照Ｌｏｎｇａ ｓ插线法 ,制备左侧局灶性脑缺血—再灌注动物模型 ,4小时后拔除插线。将大鼠随机分为 5组 ,每组 10只。 ( 1)再灌注前高硫酸镁组 (ＨＢ) ,于再灌…     

甘糖酯对高脂血症大鼠血脂及脂蛋白脂酶的调节作用

目的探讨甘糖酯调节血脂的分子机制。方法以不同剂量甘糖酯(37.8,75.6 mg·kg^-1·d^-1)给高脂血症大鼠ig给药3周,禁食12 h后,测定大鼠血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)的浓度变化,用反转录聚合酶链式反应(RT-PCR)法检测组织中脂蛋白脂酶(LPL)mRNA的表达。结果甘糖酯有降低血清TC,TG和LDL-C,升高HDL-C的作用,同时提高LPL mRNA的表达,且呈剂量依赖性关系。甘糖酯对LPL mRNA转录的促进作用与其降低TC,TG和LDL-C的作用呈正比关系。结论甘糖酯通过促进LPL mRNA转录而调节血脂水平,这可能是甘糖酯降血脂、预防动脉粥样硬化等心脑血管疾病的机制之一。     

甘糖酯对培养的牛脑微血管平滑肌细胞增殖的影响

应用牛脑微血管平滑肌细胞(BCMSMCs)体外培养技术,观察了酸性多糖药物甘糖酯(PGMS)对10％小牛血清(FCS)、白细胞介素1(IL-1)致BCMSMCs过度增殖的影响。将培养的5～8代细胞接种于96孔板,正常组加入含10％FCS的MEM培养液(或含有50u/ml IL-1的0.4％FCS培养液),给药组分别加入含有PGMS0.05、0.1、0.2、0.4、0.8、1.6mg/ml浓度的10％FCS培养液(或50u/ml IL-1的0.4％FCS培养液),以结晶紫染色,MTT比色,测定72h后细胞生长情况。结果显示,与10％FCS组和IL-1组比较,PGMS组BCMSMCs的增殖受到明显抑制(P<0.01),提示PGMS对10％FCS和IL-1引起的BCMSMCs异常增殖具有明显的抑制作用。     

甘糖酯的抗血栓作用及其作用机理

本文研究了硫酸甘糖酯(PGMS)对家兔实验性血栓形成及急性实验性肺动脉血栓栓塞的影响,并与等抗凝效价肝素进行了比较。结果提示,PGMS具有较好的抗血栓作用。为探讨其作用机理,还观察了PGMS对家兔凝血系统和纤维蛋白溶解系统的影响。研究结果提示,PGMS可通过抑制凝血系统和激活纤维蛋白溶解系统而发挥其抗血栓作用。     

甘糖酯对鹌鹑肝脏和动脉壁胆固醇及丙二醛含量的影响

甘糖酯(PGMS)是类肝素海洋药物。本文以鹌鹑高脂血症为模型观察了PGMS对鹌鹑肝脏和动脉壁胆固醇及丙二醛含量(MDA)的影响。结果表明,口服PGMS 6周,能明显抑制高脂饮食所致TC、(LDL VLDL)-C水平的升高,提高HDL-C/TC及HDL_2-C/HDL_3-C值;明显减少鹌鹑肝脏和动脉壁胆固醇含量,特别是减少胆固醇酯在动脉壁的沉积和脂质过氧化物的终末产物MDA的生成。     

甘糖酯在小鼠体内的药代动力学研究

用同位素标记法研究了[~3H]甘糖酯1次灌胃后在小鼠体内的药代动力学,其血药浓度——时间曲线符合一室开放模型。小鼠灌服[~3H]甘糖酯25mg/kg(4.48MB_q/kg)后的药动学参数为:t_(1/2)Ka 0.24h;t_(1/2)β67h,V_d921mL,Cl9.58ml/h,AUC41.45mg/(mL·h),F79.3％,PPB54.9％。该药广泛分布于肝、肾、脾、胸腺、肾上腺、肺、心、肌肉和脑内。主要经尿道与粪便排泄。     

牛磺酸对大鼠心肌缺血再灌注损伤的保护作用

目的 探讨牛磺酸对大鼠心肌缺血再灌注损伤的保护作用及其机理。方法 采用在体大鼠冠脉结扎后再通的方法,观察牛磺酸对大鼠心肌缺血再灌注后心肌梗塞的范围,血清和心肌中SOD活性、MDA和NO含量的影响。结果 牛磺酸可明显减少大鼠心肌缺血再灌注的心肌梗塞范围（P＜0．05,0．01）,提高大鼠心肌缺血再灌注后血清和心肌中的SOD活性（P＜0．01）,降低心肌和血清中MDA和NO含量（P＜0．05,0．01）。结论 牛磺酸对大鼠心肌缺血再灌注损伤具有保护作用,可能与其提高血清和心肌组织中SOD活性、降低MDA和NO含量有关。     

QN胶囊对小鼠和大鼠脑缺血的保护作用

目的探讨QN胶囊对小鼠和大鼠脑缺血损伤的保护作用及机制。方法采用小鼠密闭缺氧实验,观察QN胶囊对小鼠存活时间的影响;结扎小鼠双侧颈总动脉及迷走神经造成急性脑缺血,观察QN胶囊对小鼠存活时间的影响;选用Wistar健康大白鼠,采用急性不完全性脑缺血再灌注模型,观察QN胶囊对大鼠脑含水量、脑指数、脑毛细血管通透性、组织形态学、脑组织中的超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH Px)、一氧化氮(NO)含量的影响。结果QN胶囊可延长缺氧小鼠和急性脑缺血小鼠的存活时间;可显著降低脑缺血再灌注模型大鼠的脑含水量、脑指数、脑毛细血管通透性及脑组织中的MDA和NO的含量;显著升高SOD和GSHPx的活性。结论QN胶囊对脑缺血及再灌注损伤有保护作用。     

Effect of 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on oxidative stress in cerebral cortex of rats

The objective of this study was to verify the effect of the organochalcogen 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on some parameters of oxidative stress in the brain of 10-day-old rats. Cerebral cortex was incubated for 1 h in the presence or absence of 1, 10 or 30 μM of 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one and thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), nitric oxide (NO) production and the release of the cytosolic enzyme lactate dehydrogenase (LDH) were measured. The organotellurium was not capable to alter TBARS and carbonyl assays. In contrast, the compound at 10 and 30 μM provoked a reduced of protein thiol groups measured by the sulfhydryl assay. Furthermore, the activity of the antioxidant enzyme CAT (10 and 30 μM) and GPx (1, 10 and 30 μM) was reduced by the organochalcogen. On the other hand, the activity of SOD and GST were enhanced respectively by 1, 10 and 30 μM of the compound. Furthermore, NO production was also increased by 30 μM of this organochalcogen. Finally, we verified that the organotellurium was capable of enhance the LDH release at 30 μM concentration. Our findings indicate that this organotellurium compound induces in vitro oxidative stress in the cerebral cortex of rats being potentially toxic for the brain of rats.     

Suppression of oxidative stress and pro-inflammatory mediators by Cymbopogon citratus D. Stapf extract in lipopolysaccharide stimulated murine alveolar macrophages

Exploration of antioxidants of plant origin and their scientific validation for their immense pharmacological potential is emerging as an issue of intense research now-a-days.The effect of Cymbopogon citratus extract was seen on cell viability, oxidative stress markers i.e. ROS production, SOD activity, lipid peroxidation and GSH content of murine alveolar macrophages stressed with lipopolysaccharide. Modulation in release of NO and pro-inflammatory cytokine TNF-α along with alterations in mitochondrial membrane potential under stress were compared with known plant derived antioxidant quercetin. The extract was not found to be cytotoxic at any of the selected doses. At 5 and 10 μg the extract showed significant increase in SOD activity, GSH content (p < 0.001), decrease in ROS production as seen by fluorescent dye DCFH-DA and also MDA formation (lipid peroxidation marker) significantly. The extract also showed reduction in the release of pro-inflammatory mediators TNF-α and NO significantly indicating an anti-inflammatory effect. The extract was able to restore mitochondrial membrane potential as estimated by spectrofluorimetry using the fluorescent dye Rhodamine 123. The results suggest potential use of the cytoprotective, antioxidant and anti-inflammatory property of C. citratus in the form of dietary component and also in formulations against lung inflammatory diseases where oxidative stress plays an important role.     

Catalase and glutathione peroxidase mimics

Overproduction of the reactive oxygen species (ROS) superoxide (O₂⁻) and hydrogen peroxide (H₂O₂) are increasingly implicated in human disease and aging. ROS are also being explored as important modulating agents in a number of cell signaling pathways. Earlier work has focused on development of small catalytic scavengers of O₂⁻, commonly referred to as superoxide dismutase (SOD) mimetics. Many of these compounds also have substantial abilities to catalytically scavenge H₂O₂ and peroxynitrite (ONOO⁻). Peroxides have been increasingly shown to disrupt cell signaling cascades associated with excessive inflammation associated with a wide variety of human diseases. Early studies with enzymatic scavengers like SOD frequently reported little or no beneficial effect in biologic models unless SOD was combined with catalase or a peroxidase. Increasing attention has been devoted to developing catalase or peroxidase mimetics as a way to treat overt inflammation associated with the pathophysiology of many human disorders. This review will focus on recent development of catalytic scavengers of peroxides and their potential use as therapeutic agents for pulmonary, cardiovascular, neurodegenerative and inflammatory disorders.