通络明目膏对糖尿病大鼠视网膜血管内皮生长因子表达的影响

目的 探究通络明目膏对糖尿病大鼠视网膜血管内皮生长因子（VEGF）表达的影响。方法 选择60只实验大鼠,应用随机数表法将其分为空白组（n=10）、阳性对照组（n=10）、模型组（n=10）以及通络明目膏低剂量组（n=10）、通络明目膏中剂量组（n=10）、通络明目膏高剂量组（n=10）。除空白组外,其余5组大鼠通过高脂高糖饮食+2%链脲佐菌素注入建立糖尿病视网膜病变模型,同时通络明目膏低剂量组、通络明目膏中剂量组、通络明目膏高剂量组分别灌胃10、40、60 mg/（kg·d）通络明目膏,阳性对照组灌胃等效剂量100 mg/（kg·d）的羟苯磺酸钙胶囊,模型组、空白组灌胃等量蒸馏水,干预12周。比较各组大鼠外周血血清胰岛素样生长因子1(IGF-1)、血管内皮素（ET-1）、VEGF表达量以及大鼠视网膜组织中血管内皮生长因子受体2(VEGFR-2)、VEGF表达量的差异。结果 干预12周后,模型组大鼠视网膜组织VEGFR-2、VEGF阳性表达以及血清IGF-1、ET-1、VEGF表达量显著高于其他5组（P <0.05）。通络明目膏低剂量组的血清IGF-1、ET-1、VEGF表达量及视...     

通络明目膏对糖尿病视网膜病变大鼠微血管的保护作用及其作用机制研究

目的 探究通络明目膏对糖尿病视网膜病变大鼠微血管的保护作用,并分析其可能作用机制。方法选择60例SD大鼠作为实验对象,应用随机数表法将其分为6组,每组各10只。其中,空白组大鼠正常饮食水,阳性对照组、模型组、中药低剂量组、中药中剂量组、中药高剂量组以高脂高糖饮食联合注射2%链脲佐菌素溶液建立糖尿病视网膜病变大鼠模型。实验开始时,中药低剂量组、中药中剂量组、中药高剂量组分别灌胃通络明目膏10、40、60 mg/（kg·d）,阳性对照组灌胃等效剂量100 mg/（kg·d）羟苯磺酸钙胶囊,模型组和空白组灌胃等效剂量生理盐水。干预12周后,观察比较各组大鼠视网膜血管周细胞数、血管内皮细胞数、伊文思蓝（EB）渗透量以及视网膜组织中血管内皮细胞生长因子受体2(VEGFR-2)、血管内皮生长因子（VEGF）表达情况。结果 中药低剂量组、中药中剂量组、中药高剂量组、阳性对照组大鼠视网膜血管周细胞数显著高于模型组,血管内皮细胞数、EB渗透量显著低于模型组（P <0.05）,且中药低剂量组与阳性对照组上述各项指标比较差异无统计学意义（P> 0.05）,而中药低剂量组、中药中剂量组、中药高剂量...     

银杏叶提取物对糖尿病大鼠视网膜神经节细胞凋亡的作用观察

目的 观察银杏叶提取物（EGB）对糖尿病大鼠视网膜神经节细胞凋亡的影响,探讨EGB防治糖尿病性视网膜病变的作用机制. 方法 选择健康成年Wistar 大鼠50只, 随机分成正常对照组、模型组、低剂量EGB组、中剂量EGB组、高剂量EGB组.腹腔内注射链脲佐菌素（STZ） 诱发大鼠糖尿病.低、中和高剂量EGB组分别给予EGB溶液50 ,100和200 mg·kg^-1·d^-1,灌胃给药,模型组和正常组均灌胃等体积0.9%氯化钠溶液,均连续12周.制备大鼠视网膜石蜡切片行末端脱氧核苷酸转移酶介导的dUTP缺口末端标记 （TUNEL） 法, 检测视网膜神经节细胞凋亡指数（AI）,并对染色结果行计算机图像分析.电镜观察各组神经节细胞的超微结构变化. 结果 模型组大鼠神经节细胞AI比正常对照组显著增加（P＜0.01), 中、高剂量EGB组神经节细胞AI与模型组比较明显减少（P＜0.01),低剂量EGB组神经节细胞AI与模型组比较差异无显著性（P＞0.05）.中、高剂量EGB组神经节细胞超微结构的损害明显减轻. 结论 EGB可以通过抑制视网膜神经节细胞的凋亡来减轻糖尿病性视网膜病变.     

滋阴明目汤联合复方血栓通胶囊治疗单纯性糖尿病视网膜病变

目的：观察滋阴明目汤联合复方血栓通胶囊对单纯性糖尿病性视网膜病变患者视功能恢复的治疗作用。方法收集糖尿病性视网膜病变I～Ⅲ期的患者共52例（92眼）。随机分成两组,观察组29例（49眼）,给予滋阴明目汤联合复方血栓通胶囊治疗;对照组23例（43眼）,予羟苯磺酸钙胶囊治疗。两组分别连续用药3个月,观察患者治疗前后视力、眼底、视野、荧光血管造影及视觉电生理的变化。结果观察组的视力较治疗前明显提高,与对照组比较,差异有统计学意义（P＜0.05）。观察组视网膜小出血斑、微血管瘤数目及视野灰度值（MD）较治疗前明显减少,与对照组比较,差异有统计学意义（P＜0.05）。结论滋阴明目汤联合复方血栓通胶囊对糖尿病性视网膜病变患者视力的改善有显著疗效,对视网膜微血管瘤和小出血斑有良好的控制作用,对视功能的恢复有积极作用。     

金乌健骨方对关节炎模型大鼠的抗炎作用研究

目的观察金乌健骨方对胶原诱导性关节炎（CIA）大鼠血清肿瘤坏死因子α（TNF α）、白细胞介素1（IL 1）及白细胞介素1β（IL 1β）水平的影响,探讨其作用机制。方法将60只Wistar大鼠随机分为空白对照组,模型对照组,金乌健骨方高、中、低剂量组和雷公藤多苷对照组,每组10只。除空白对照组外,其余各组制备CIA模型。给药组分别于造模后第3周开始连续灌胃给药4周,并于用药前及用药后每周观测CIA大鼠关节肿胀程度和关节炎指数,给药结束后检测血清TNF α、IL 1及IL 1β。结果金乌健骨方高、中剂量组关节肿胀程度和关节炎积分均明显降低,优于雷公藤多苷对照组（P＜0.01,P＜0.05）。与模型组比较,金乌健骨方高、中剂量组大鼠血清TNF α、IL 1、IL 1β表达水平显著下降（P＜0.01）,与雷公藤多苷对照组相当;高、中剂量金乌健骨方对IL 1β的影响优于雷公藤多苷（P＜0.01）。结论金乌健骨方能减轻CIA大鼠关节肿胀程度,降低关节炎积分,下调CIA大鼠血清TNF α、IL 1及IL 1β的表达。     

羟苯磺酸钙改善糖尿病大鼠视网膜病变及其机制研究

目的观察羟苯磺酸钙对糖尿病大鼠视网膜病变的影响并探讨其机制.方法以65 mg/kg一次性ip链脲佐菌素诱导糖尿病模型,将糖尿病模型大鼠分为模型组、复方血栓通组(1.05 g/kg)和羟苯磺酸钙组(0.334 g/kg),另设对照组,均ig给药,1次/d,对照组给予等剂量蒸馏水,共12周.采用Real-time PCR法检测Ⅳ型胶原及血管内皮生长因子(VEGF) mRNA 在视网膜组织中的表达;光镜下观察视网膜血管形态学改变,测定视网膜毛细血管面积密度;透视电镜观察大鼠视网膜超微结构.结果与对照组比较,模型组大鼠视网膜Ⅳ型胶原mRNA表达升高(P<0.05),VEGF mRNA升高(P<0.01),毛细血管面积密度显著增高(P<0.001).与模型组比较,羟苯磺酸钙组大鼠视网膜Ⅳ型胶原mRNA、VEGF mRNA表达和毛细血管面积密度均降低(P<0.05).结论 羟苯磺酸钙能下调视网膜中Ⅳ型胶原、VEGF的表达,抑制纤维组织增生和血管新生,从而改善糖尿病视网膜病变.     

注射用益气复脉（冻干）对阿霉素所致心肌损伤大鼠药效及肠道菌群的影响

目的 探讨注射用益气复脉（冻干）（YQFM）对阿霉素导致的心肌损伤大鼠的药效作用及对肠道菌群的影响。方法 将24只阿霉素导致心肌损伤模型成功的SD大鼠随机分为3组：模型组和YQFM低、高剂量（464.3、928.6 mg·kg^-1）组,另取8只健康SD大鼠为对照组。每天尾iv给药1次,连续14 d,对照组和模型组尾iv 0.9%氯化钠注射液。给药过程中观察大鼠状态并称体质量。给药结束后,酶联免疫吸附（ELISA）法检测大鼠血清中超氧化物歧化酶（SOD）、丙二醛（MDA）、乳酸脱氢酶（LDH）和肌酸激酶（CK）水平;取出心脏进行HE染色观察病理改变;取出盲肠位置粪便,进行高通量16S rRNA测序分析。结果 对照组大鼠一般状态正常,模型组出现毛色变差、厌食、腹胀、腹泻、口鼻出血、眼球出血的动物数明显多于给药组;与对照组比较,模型组大鼠体质量显著降低（P<0.001）;与模型组比较,YQFM低、高剂量组的大鼠体质量显著上升（P<0.01、0.001）。与对照组相比,模型组MDA、LDH、CK水平均显著升高,SOD活性显著性下降（P<0.001） ;与模型组比较,YQFM低、高剂量组MDA、LDH、CK水平显著下降,SOD活性显著升高（P<0.001）。HE结果显示,对照组心肌细胞排列整齐,模型组有心肌细胞溶解和出血现象,给予YQFM后心肌细胞溶解和出血现象减轻。Alpha多样性分析结果显示,与对照组相比,模型组肠道菌群的多样性和丰度均显著下降（P<0.05、0.01） ;与模型组比较,YQFM组肠道菌群的多样性和丰度显著上升（P<0.05、0.01、0.001）。距离矩阵与PCoA分析结果显示,给药组和对照组之间的差异比模型组和对照组的差异小。肠道丰度的结果显示,与对照组相比,模型组在门和属的水平上的菌群数量均显著减少（P<0.01） ;与模型组比较,YQFM低剂量组在门的水平上和低、高剂量组在属的水平上菌群数量均显著增加（P<0.01、0.001）。在菌群物种的组成差异度分析中,与模型组比较,给予YQFM后有助于有益菌的生长和抑制致病菌生长（P<0.05、0.01、0.001） ;在肠道菌群均匀度的分析中,与对照组比,模型组的肠道菌群均匀度降低,给予YQFM后,肠道菌群的均匀度恢复。结论 YQFM对阿霉素导致的大鼠心肌损伤发挥改善作用,并且可改善心肌损伤造成的肠道菌群多样性及丰度下降,抑制致病菌的生长,促进有益菌的生长。     

芍药二酮对糖尿病视网膜病变大鼠血管损伤及NLRP3活性的影响

目的 探究芍药二酮对链脲佐菌素诱导的糖尿病视网膜病变中视网膜血管炎性和血管通透性的影响及分子机制.方法 采用腹腔注射链脲佐菌素(STZ)建立糖尿病视网膜病变大鼠模型,随机将 SD大鼠分为对照组、模型组、芍药二酮低剂量组(25 mg/kg)、中剂量组(50 mg/kg)、高(100 mg/kg)剂量组.给药结束后,摘眼球...     

益气明目口服液对光化学损伤大鼠视网膜保护作用的研究

目的:研究益气明目口服液对光化学损伤大鼠视网膜的保护作用。方法:48只SD大鼠随机分为阴性对照组、模型组及益气明目口服液高、低剂量组。除阴性对照组外,各组大鼠接受(1 900±106.9)Lux绿色荧光灯24h持续光照射,制备大鼠视网膜光化学损伤模型。益气明目口服液高、低剂量组分别于光照前7d灌胃给药30、15mL.kg-1.d-1;阴性对照组及模型组予以等量生理盐水灌胃。光照后6h、6d、14d检测视网膜组织中超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,并进行视网膜透视电子显微镜和光学显微镜的组织学观察。结果:光化学损伤后6d及14d,益气明目口服液高剂量组视网膜中SOD的活性显著高于模型组(P<0.05),益气明目口服液高、低剂量组视网膜中MDA的含量均显著低于模型组(P<0.05);通过视网膜透视电子显微镜和光学显微镜的组织学观察,益气明目口服液高、低剂量组的病理组织学损害较模型组显著减轻。结论:益气明目口服液对视网膜光化学损伤有显著的保护作用。     

注射用益气复脉（冻干）对慢性心力衰竭大鼠肠道菌群的影响

目的 探讨注射用益气复脉（冻干）（YQFM）对慢性心力衰竭（CHF）大鼠的肠道菌群的影响。方法 采用腹主动脉缩窄法制备CHF大鼠模型，选取造模成功的大鼠随机分为3组：模型组和YQFM低、高剂量（464.3、928.6 mg·kg^-1，464.3 mg·kg^-1为临床等效剂量）组；假手术组大鼠进行切口和缝合，但不进行结扎缩窄。每天尾iv给药1次，连续给药14 d，假手术组和模型组尾iv给予0.9%氯化钠注射液。给药前后采用超声诊断仪检测大鼠心功能；给药14 d后取血，ELISA法检测大鼠血清心钠肽（ANP）、脑钠肽（BNP）、肌酸激酶同工酶（CK-MB）、内皮素（ET）、丙二醛（MDA）水平；取出盲肠位置粪便，进行高通量16S rRNA测序分析。结果 与模型组比较，YQFM组大鼠的左室短轴缩短率（LVFS）和左室射血分数（LVEF）均显著升高（P＜0.01、0.001），ANP、BNP、CK-MB、ET、MDA水平均显著下降（P＜0.001）。Venn图结果显示，CHF模型可以使大鼠肠道菌群数量下降；α多样性分析结果显示，与模型组比较，YQFM组的Chao1、Shannon、Simpson指数均显著上升（P＜0.05、0.01）；在非度量多维尺度（NMDS）和主坐标分析（PCoA）中，YQFM组与假手术组的差异比模型组与假手术组的差异小；在门水平下，与模型组相比，YQFM组的厚壁菌门相对丰度升高，高剂量组差异显著（P＜0.01），YQFM组的拟杆菌门相对丰度有降低趋势，YQFM低、高剂量组的厚壁菌门/拟杆菌门（F/B）呈升高趋势。在丰度等级曲线中，模型组与假手术组的差距大，YQFM组更接近假手术组，肠道菌群的均匀度明显回升。结论 YQFM改善CHF大鼠的心功能，缓解炎症反应，改善肠道菌群紊乱。     

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.     

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.     

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.