机械生长因子E肽在产后压力性尿失禁模型大鼠中的作用

目的通过尿道横纹括约肌及肛提肌局部注射机械生长因子E肽(MGF-Ct24E),观察其在产后压力性尿失禁(PPSUI)模型大鼠中的作用。方法 116只雌性未孕SD大鼠,随机选取16只作为正常对照组,不做处理;剩余100只模拟妊娠分娩难产产伤建立PPSUI模型大鼠。将建模成功的64只PPSUI模型大鼠随机分为4组:生理盐水对照组,尿道中段及肛提肌注射无菌0.9%氯化钠注射液各10μl;实验1组,尿道中段及肛提肌各注射MGF-Ct24E 10μl,浓度0.1μg/μl;实验2组,尿道中段注射MGF-Ct24E,剂量浓度同上,肛提肌中注射无菌0.9%氯化钠注射液10μl;实验3组,尿道中段注射无菌生理盐水,肛提肌注射MGF-Ct24E,剂量浓度同上,各组16只。分别于注射后7、14 d(8只/次)行尿动力学检测各组最大膀胱容量(MBC)和漏尿点压力(LPP),随后处死大鼠,提取各组尿道中段及肛提肌行苏木精-伊红(HE)染色,观察各组尿道横纹括约肌和肛提肌组织的形态学变化。结果注射治疗后7 d LPP及MBC比较:各实验组与0.9%氯化钠注射液对照组之间差异无统计学意义,各组均低于正常对照组(P<0.01)。注射治疗后14 d LPP及MBC比较:实验1组高于实验2组、3组及0.9%氯化钠注射液对照组(P<0.01),低于正常对照组,差异无统计学意义;实验2组、3组较0.9%氯化钠注射液对照组高(P<0.01),实验2组较实验3组高,差异无统计学意义。PPSUI大鼠尿道横纹括约肌及肛提肌损伤后肌组织出现断裂、萎缩、结构紊乱、含量减少,随着时间点延长,出现逐渐修复现象,有部分纤维瘢痕形成。结论肛提肌及尿道括约肌局部注射MGF-Ct24E能提高PPSUI大鼠LPP和MBC、能促进组织损伤后修复,对PPSUI大鼠可能有治疗作用,括约肌联合肛提肌注射治疗可能较单一注射治疗PPSUI大鼠效果更好。     

黄芪注射液对脓毒性休克大鼠循环功能的影响

目的 观察静脉给予黄芪注射液是否对脓毒性休克大鼠模型存在抗休克作用,并对机制进行初步探讨.方法 Wistar大鼠30只分3组,对照组(n=10):0 min开始经股静脉连续注射0.9%氯化钠溶液1 ml·kg-1·h-1,20 min后经颈静脉连续注射0.9%氯化钠溶液;模型组(n=10):0 min开始经股静脉脂多糖...     

维生素E对多柔比星所致生殖毒性雄性大鼠的保护作用

目的探讨维生素E对多柔比星致生殖毒性雄性大鼠的保护作用。方法通过一次性静脉注射多柔比星7.5 mg.kg-1制备多柔比星致雄性大鼠生殖毒性损伤模型。维生素E组(n=8)从造模前1 d起,灌服维生素E 100mg.d-1连续14 d。模型组(n=8)造模后,每日经腹腔注射0.9%氯化钠溶液1 mL。对照组(n=8)不造模,每日经腹腔注射0.9%氯化钠溶液1 mL。通过观察大鼠血清超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量和睾丸病理组织学变化评估多柔比星对雄性大鼠生殖毒性作用。结果与对照组比较,模型组大鼠血清SOD活性降低,MDA含量升高(P<0.05),睾丸重量和睾丸系数降低(P<0.05),精曲小管生精细胞明显减少,精母细胞和精子细胞退变,部分坏死、脱落。维生素E组大鼠血清SOD活性和MDA含量与对照组比较差异无显著性(P>0.05),睾丸重量和睾丸系数的变化和睾丸病理损伤程度轻于模型组。结论维生素E对多柔比星所致生殖毒性雄性大鼠具有保护作用,其药理作用机制与提高机体抗氧化能力、抑制脂质过氧化反应有关。     

依达拉奉促进大鼠脊髓损伤神经功能恢复作用研究

目的 观察依达拉奉对急性脊髓损伤大鼠神经功能评分的影响，探讨依达拉奉促进大鼠脊髓损伤神经功能恢复的作用。方法 采用改良Allen法制作SD大鼠脊髓中度损伤模型，将模型鼠随机分为实验组和对照组各16只。实验组按3 mg·kg^-1的剂量将依达拉奉用0.9%氯化钠溶液稀释后，每隔12 h腹腔注射1次，给药时间为30 min，共14 d。对照组采用同样方式给予0.9%氯化钠溶液。比较实验开始后不同时间大鼠斜板试验、神经功能评分变化。结果 从伤后2周和3周起，实验组的斜板最大角度和神经功能评分分别与对照组比较均差异有极显著性（均P＜0.01）。结论 依达拉奉对大鼠脊髓损伤神经功能的恢复具有促进作用。     

乌司他丁对大鼠缺血-再灌注损伤肝脏的保护作用

目的 研究乌司他丁对大鼠肝脏缺血-再灌注后肝细胞线粒体的保护作用. 方法 30只SD大鼠随机分为3组：假手术对照组、模型对照组、药物实验组, 每组10只. 大鼠肝脏缺血-再灌注模型为阻断肝门30 min, 再灌注120 min. 缺血前30 min, 假手术对照组、模型对照组经尾静脉注入0.9%氯化钠溶液2 mL, 药物实验组经尾静脉注入含乌司他丁（5万U&#8226;kg-1）的0.9%氯化钠溶液2 mL. 再灌注后立即检测肝细胞线粒体的细胞色素C、三磷腺苷（ATP）含量及超氧化物歧化酶(SOD)活性和丙二醛（MDA）含量. 结果再灌注后, 模型对照组细胞色素C、ATP含量及SOD活性显著低于假手术对照组（P<0.01）, MDA含量高于假手术对照组（P<0.01）;药物实验组细胞色素C、ATP含量及SOD活性显著高于模型对照组（P<0.05或P<0.01）, MDA含量低于模型对照组（P<0.01）. 结论乌司他丁对大鼠肝脏缺血再灌注后肝细胞线粒体具有保护作用.     

缬草提取物对大鼠实验性肺纤维化的干预作用

目的 探讨缬草提取物对博莱霉素所致大鼠肺间质纤维化的干预作用及其机制。方法 健康Wistar大鼠气管内一次性注入博莱霉素5 mg&#8226;kg –1制作肺纤维化模型，取造模存活大鼠65只，随机分为缬草低、高剂量组和秋水仙碱组各16只，模型组17只。造模后第2天始分别灌胃给予缬草提取物100，20 mg&#8226;kg-1和秋水仙碱100 μg&#8226;kg–1，以及0.9%氯化钠溶液10 mL&#8226;kg-1，每天1次。各组于第7天处死大鼠6只，第28天处死剩余大鼠。另取8只正常大鼠，气管内一次性注入0.9%氯化钠溶液1.0 mL&#8226; kg –1，灌胃给予0.9%氯化钠溶液10 mL&#8226; kg–1作为健康对照组，于第28天处死。大鼠处死后，取右下肺叶做HE染色和Masson染色观察肺组织结构改变；免疫组织化学法检测肺组织中的转化生长因子β1（transforming growth factor β1,TGF β1）表达改变；取左下肺叶检测羟脯氨酸（HYP）含量。结果模型组大鼠观察期内死亡3只（18.75%），7 d肺组织呈现重度肺泡炎改变合并有TGF β1表达显著升高，28 d肺组织胶原纤维重度增生并HYP水平显著升高；缬草不同剂量组及秋水仙碱组第7天肺泡炎较模型组减轻，TGF β1表达较模型组弱（P＜ 0.05)，第28天缬草不同剂量组及秋水仙碱组肺纤维化病变较模型组减轻，羟脯氨酸含量较模型组低（P＜0.05)。结论缬草提取物可以有效防治博莱霉素诱导的大鼠肺泡炎及肺纤维化，其机制可能是降低TGF β1表达。     

畅肺防喘方对哮喘模型大鼠支气管肺泡灌洗液中白细胞及嗜酸性粒细胞的影响

目的 观察畅肺防喘方对大鼠支气管肺泡灌洗液（BALF）中白细胞（WBC）及嗜酸性粒细胞（eosinophils,EOS）的影响. 方法 SD雄性大鼠60只,随机分为6组,每组10只. 大鼠于第1天皮下注射含卵蛋白1 mg,氢氧化铝200 mg的0.9%氯化钠溶液1 mL,同时腹腔注射百日咳杆菌疫苗6×10⁹个作免疫增强剂. 正常对照组仅腹腔注射0.9%氯化钠溶液1 mL. 第15天雾化吸入2%卵蛋白激发,qd,每次30 min,连续7 d. 正常对照组吸入0.9%氯化钠溶液. 低、中和高剂量药物组于致敏后第8天开始灌胃给药,分别给予畅肺防喘方大、中、小剂量,相当于生药33.8,16.9,8.5 g&#8226;kg^-1&#8226;d^-1,分早晚2次给药; 阳性对照组给予地塞米松0.75 mg&#8226;kg^-1&#8226;d^-1; 正常对照组和模型对照组给予等量0.9%氯化钠溶液,给药容积为20 mL&#8226;kg^-1,连续7 d. 观察WBC及EOS的变化. 结果 模型对照组BALF中WBC总数、EOS及百分比与正常对照组比较,均明显升高（P＜0.01）,说明哮喘模型大鼠炎症反应较强; 经过治疗后,WBC总数、EOS及百分比均明显降低,说明炎症反应减轻,其中高、中剂量药物及地塞米松均可降低显著模型大鼠肺泡灌洗液中的WBC及EOS（P＜0.05或P＜0.01）. 结论 畅肺防喘方可显著抑制哮喘大鼠BALF中炎症细胞上升,尤其是对EOS的抑制作用更为明显,说明其治疗和预防作用可能通过降低炎症反应,降低EOS水平,起到抗气道炎症反应作用.     

神经生长因子对神经源性痛大鼠脊髓保护作用研究

目的 探讨神经生长因子对神经源性痛大鼠脊髓的保护作用及其机制。方法 取成年雄性Wistar大鼠66只，随机分为3组，神经生长因子组30只，结扎坐骨神经后腹腔注射神经生长因子，20 μg·kg^-1;0.9%氯化钠溶液组30只，结扎左侧坐骨神经中段后腹腔注射等量0.9%氯化钠溶液;假手术组6只，手术仅暴露而不结扎坐骨神经。于术前和术后6 h、1，3，7，14 d分别进行行为学测定，记录大鼠缩爪与尾弹时间。应用免疫组织化学方法和图像分析系统检测脊髓中TNF-α和IL-6的表达，采用TUNEL法观察脊髓神经元凋亡，采用HE染色及尼氏染色法观察脊髓的病理形态学变化。结果 与0.9%氯化钠溶液组比较，神经生长因子组大鼠脊髓TNF-α和IL-6表达降低，脊髓神经元凋亡指数降低且疼痛减轻(均P＜0.01)。 病理学检查显示，神经生长因子组脊髓组织损伤程度较0.9%氯化钠溶液组明显减轻。结论 神经生长因子对大鼠脊髓有保护作用。其机制可能与抑制促炎性细胞因子的表达，从而抑制神经元凋亡和疼痛有关。     

鞘内注射芬太尼对糖尿病周围神经病变大鼠脊髓TNF-α表达的影响

目的 观察芬太尼对糖尿病周围神经病变模型大鼠脊髓肿瘤坏死因子α（TNF-α）表达的影响,以及其脊髓保护作用,探讨其镇痛机制。方法 成年雌性Wistar大鼠70只,随机取10只设为正常对照组（A组）,腹腔注射0.9%氯化钠溶液3 mL&#8226;kg 1&#8226;d 1;其余大鼠腹腔注射链脲菌素（STZ）建立糖尿病模型,得48只糖尿病模型大鼠。对照组和糖尿病模型大鼠实施鞘内置管,分别成功8只和32只。A组8只鞘内各注射0.9%氯化钠注射液10 μL;将糖尿病大鼠随机等分为2组,糖尿病对照组（B组）16只鞘内注射与A组等体积0.9%氯化钠注射液;芬太尼治疗组（C组）16只鞘内注射芬太尼0.5 μg&#8226;（10 μL）^-1;于给药后第1,2,3,4周分别进行行为学测定,记录机械缩足阈值;取脊髓切片,用尼氏染色法观察脊髓的病理形态学改变;应用免疫组化方法和图象分析系统检测脊髓背角TNF-α的表达。结果 与A组比较,B、C组大鼠机械缩足阈值降低（均P＜0.05）,脊髓背角组织中TNF-α表达显著升高（均P＜0.01）;与B组比较,C组机械缩足阈值升高 （P＜0.05）,TNF-α表达显著降低（P＜0.01）。尼氏染色显示,B组大鼠脊髓尼氏小体呈现破碎和溶解性改变,鞘内注射芬太尼可改善尼氏小体的变化。结论 糖尿病大鼠周围神经病变引起的神经痛与脊髓背角促炎性细胞因子TNF-α有关。鞘内注射芬太尼对脊髓有保护作用,并可明显抑制脊髓背角TNF-α的表达,减轻糖尿病神经痛。     

低剂量精氨酸血管加压素提高大鼠空间学习与记忆能力研究

目的 探讨多次外周给予低剂量精氨酸血管加压素（AVP）对大鼠空间学习和记忆能力的影响。方法分别将不同剂量(0.5,1.0 μg&#8226;kg 1) AVP或0.9%氯化钠溶液0.12 mL（对照组）于每次训练前30 min经皮下注入Wistar大鼠体内,采用Morris水迷宫检测对大鼠学习和记忆能力的影响及其量 效关系。结果皮下注射0.5和1.0 μg&#8226;kg 1AVP组大鼠在4 d训练中,隐匿平台试验中潜伏期和潜伏距离与对照组比较差异无显著性。空间搜索实验显示,0.5和1.0 μg&#8226;kg 1AVP组大鼠在原平台象限游泳时间百分比和距离百分比均明显高于对照组,各组大鼠寻找平台的动机和视敏度差异无显著性。结论训练前经外周多次注射低剂量AVP可提高大鼠长期记忆能力。     

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.     

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.     

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.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.