诱导血红素加氧酶-1对肝硬化大鼠肠黏膜屏障的保护作用

目的 探讨血红素加氧酶-1(HO-1)对肝硬化大鼠肠黏膜屏障的保护作用.方法 建立四氯化碳(CCl4)致大鼠肝硬化动物模型,钴原卟啉诱导HO-1表达.FITC-荧光标记法检测大鼠肠黏膜通透性.ELISA法检测血浆TNF-α及IL-6含量.分光光度法检测肠组织HO活性及MDA含量.TUNEL染色法检测肠黏膜细胞凋亡.Western blot检测肠组织Bcl-2蛋白表达.结果 与control组比较,肝硬化(HC)组大鼠肠道通透性显著增高(P＜0.01);HC+HO组大鼠肠道通透性比HC组显著降低(P＜0.05).血浆TNF-α水平在HC组显著高于control组(P＜0.01),而在HC+HO组显著低于HC组(P＜0.05);IL-6水平在HC组显著高于control组(P＜0.01).肠组织匀浆MDA含量在HC组显著高于control组(P＜0.01),而在HC+HO组显著低于HC组(P＜0.01).诱导HO-1可有效抑制肝硬化大鼠肠黏膜细胞凋亡.HC组大鼠Bcl-2蛋白表达量显著低于control组(P＜0.01),诱导HO-1可使Bcl-2蛋白表达量显著高于control组(P＜0.01).结论 诱导HO-1可能通过抑制炎症与细胞凋亡保护肝硬化大鼠肠黏膜屏障.     

肾衰养真胶囊对CRF营养不良模型大鼠NPY及NPY mRNA表达的影响

目的 探讨肾衰养真胶囊改善慢性肾衰竭(CRF)营养不良的作用机理.方法 采用0.5%腺嘌呤+4%酪蛋白饲料喂养4周制作CRF营养不良大鼠模型32只,随机分为模型组、肾衰养真胶囊(实验)组和复方α-酮酸(开同)组,另取正常大鼠8只为对照组.4周后,腹主动脉采血,检测血肌酐(SCr)、尿素氮(BUN)、24 h尿蛋白(24 h Upr)、白蛋白(Alb)、血红蛋白(Hb)、血浆神经肽Y(NPY)、下丘脑NPY mRNA表达水平.结果 与模型组和开同组比较,实验组大鼠24 h Upr减少、NPY降低(P＜0.01,P(0.05),下丘脑NPY mRNA表达卜调(P＜0.01).结论 肾衰养真胶囊可改善CRF营养不良,其机制可能是通过降低血浆NPY水平和上调下丘脑NPY mRNA表达.     

木糖醇对糖尿病大鼠肾小管环氧化酶-2表达的影响

目的:探讨不同剂量木糖醇对糖尿病大鼠肾小管环氧化酶-2(COX-2)表达的影响.方法:将大鼠随机分为正常对照组、糖尿病对照组、5%木糖醇组(低剂量组)、10%木糖醇组(中剂量组)和20%木糖醇组(高剂量组).第8周末,测定每组大鼠血清及尿液中尿酸、尿囊素和肌酐水平,取肾脏测定肾小管COX-2免疫组化表达情况.结果:(1)血尿酸、尿囊素水平在低、中剂量组高于糖尿病对照组,其中中剂量组升高差别有统计学意义(P＜0.05);高剂量组低于糖尿病对照组(P＞0.05).(2)尿尿酸水平在低、中剂量组尿尿酸低于糖尿病对照组,但差异无统计学意义(P＞0.05),低、中剂量尿尿囊素低于糖尿病对照组(P＜0.05);高剂量组尿尿酸、尿囊素高于糖尿病对照组(P＜0.05).(3)尿酸清除分数在低、中剂量组低于糖尿病对照组(P＜0.05);高剂量组高于糖尿病对照组(P＜0.05).(4)肾小管COX-2表达与糖尿病对照组相比,低、中剂最组呈高表达(P＜0.05),高剂量组则呈低表达(P＜0.05).结论:低、中剂量木糖醇致血尿酸水平升高,COX-2表达增强,加重肾小管的损伤.高剂量木糖醇可使糖尿病大鼠尿酸排泄增加,血尿酸水平降低,肾小管COX-2表达降低.     

发育期大鼠高热惊厥脑损伤CO变化及Znpp对其影响

目的:研究锌原卟啉对大鼠高热惊厥脑损伤CO变化的影响及作用机制.方法:21日龄Wistar大鼠,随机分为对照组、高热未惊厥组、FC组及Znpp治疗组.采用热水浴诱导FC大鼠动物模型和Znpp治疗模型.用分光光度计检测各组大鼠脑组织匀浆和血浆CO含量,用HE染色观察大鼠海马神经元形态学改变.结果:FC组血浆CO含量明显升高,与对照组、高热未惊厥组及Znpp治疗组比较,有显著性差异(P＜0.01),Znpp治疗组血浆CO含量升高与高热未惊厥组比较,亦有显著性差异(P＜0.05);FC组脑组织匀浆CO含量增高,与对照组、高热未惊厥组及Znpp治疗组比较有显著性差异(P＜0.01),Znpp治疗组脑组织匀浆CO含量升高,与对照组、高热未惊厥组比较有显著性差异(P＜0.01),高热未惊厥组与对照组比较差异无显著性(P＞0.05);结论:FC能够引起脑损伤且CO水平增高, Znpp能够使CO水平下降,对脑损伤有保护作用.     

槲皮素对大鼠慢性肾功能衰竭及促红细胞生成素水平的影响

目的:探讨腺嘌呤诱导大鼠慢性肾功能衰竭(CRF)模型的特点及中药成分槲皮素对CRF的作用及对促红细胞生成素(EPO)水平的影响.方法:以喂饲0.75%腺嘌呤制成大鼠CRF模型后,灌胃给予槲皮素100 mg·kg-1·d-1,共喂药8周,观察治疗组与肾衰组病理变化,测定大鼠肾功能、肾组织羟脯氨酸及血浆和肾组织EPO含量.结果:治疗组肾组织病理损害明显轻于肾衰对照组;血浆BUN、Scr、肾组织羟脯氨酸含量明显下降(P＜0.01);血浆和肾组织中EPO的含量均明显升高(P＜0.01).结论:槲皮素对防治CRF有显著效果并能有效提高CRF时血浆及肾组织中EPO含量及减轻肾间质纤维化.     

地塞米松对野百合碱诱导肺动脉高压模型大鼠血管活性物质的影响

目的 探讨地塞米松早期干预对野百合碱(MCT)诱导肺动脉高压(PAH)大鼠肺血管活性物质的影响.方法 成年雄性SD大鼠30只随机均分为对照(C)组、MCT模型(M)组、MCT+地塞米松(MD)组.建立MCT诱导PAH模型,应用放射免疫法观察血浆一氧化氮(NO)和内皮素1(ET-1)水平的变化.结果 注射MCT3周后,M组大鼠肺动脉平均压(mPAP)显著高于C组和MD组(P＜0.05);与C组和MD组比较,M组血浆ET-1含量升高,NO含量降低(P＜0.05);而MD组ET-1和NO含量与C组比较无统计学差异.结论 地塞米松能抑制MCT诱导的PAH大鼠血浆中的ET-1含量升高和NO含量降低,从而改善内皮细胞功能,降低PAH.     

甘氨酸对烧伤大鼠失控炎症反应的调控作用及机制研究探讨

目的 探讨对于烧伤大鼠采用甘氨酸调控过度炎症反应的作用及其相关机制.方法 本次研究主要是通过对大鼠腹腔巨噬细胞内游离钙离子浓度影响的分析来确定甘氨酸对烧伤大鼠失控炎症反应的调控作用.结果 3、6、12、24 h,烧伤合并脓毒症组血浆LPS水平与其他3组比较,差异具有统计学意义(均P＜ 0.05).3h,烧伤合并脓毒症组血浆TNF-α水平与单纯烧伤组比较,差异具有统计学意义(P＜0.05);6、12h,烧伤合并脓毒症组TNF-α水平与其他3组比较,差异具有统计学意义(均P＜ 0.05);24h,烧伤合并脓毒症、谷氨酰胺治疗组TNF-α水平与其他3组比较,差异具有统计学意义(均P＜ 0.05).:3h,4组大鼠血浆IL-10水平整体比较,差异无统计学意义(均P＞0.05);6h,烧伤合并脓毒症、甘氨酸治疗组血浆IL-10水平与其他3组比较,差异具有统计学意义(均P＜0.05);12、24 h,烧伤合并脓毒症、甘氨酸治疗组血浆IL-10水平与烧伤合并脓毒症、谷氨酰胺治疗组比较,差异具有统计学意义(均P＜ 0.05).结论 Gln及Gly在临床上具有抗炎及抗脓毒症作用,能够在一定程度上降低烧伤后脓毒症大鼠血浆LPS水平以及抑制炎性细胞因子TNF-α分泌,并促进抗炎因子IL-10分泌.     

炎性反应和交感神经系统在慢性心力衰竭大鼠中枢调控中的相互作用

目的 探讨慢性心力衰竭(CHF)大鼠免疫炎性反应和交感神经系统在中枢调控中的相互作用.方法 36只Sprague Dawley大鼠随机分为假手术组、冠状动脉结扎组和中枢干预组,每组12只.冠状动脉结扎组和中枢干预组采用结扎冠状动脉前降支的方法制备大鼠CHF模型,假手术组仅穿线不结扎.中枢干预组术后采用血管紧张素Ⅱ(AT1)受体阻断剂一氯沙坦中枢干预,检测3组大鼠基础交感神经活动水平、心功能、儿茶酚胺及炎性因子水平.结果 与假手术组比较,CHF大鼠交感神经活动水平明显增强,血浆及中枢肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)和去甲肾上腺素(NE)水平均明显升高,心功能减退(P＜0.05);与冠状动脉结扎组比较,中枢干预组交感神经活动水平降低,血浆及中枢TNF-α、IL-1 β和血浆NE水平下降,心功能增强(P＜0.05).结论 抑制CHF大鼠中枢肾素血管紧张素系统,可降低交感系统兴奋性及免疫炎性反应,改善心功能.     

免疫球蛋白联合血浆置换治疗重症肌无力的疗效观察及对免疫细胞因子水平的影响

目的 分析免疫球蛋白+血浆置换在重症肌无力(MG)中的应用效果,观察对患者免疫细胞因子的影响.方法 纳入本院收治的重症肌无力患者48例,随机分成实验组与对照组各24例,对照组为血浆置换治疗,实验组在此基础上加用免疫球蛋白,比较两组治疗效果、肿瘤坏死因子-α(TNF-α)、白介素-2(IL-2)以及免疫细胞水平.结果 实验组有效率为95.83％,高于对照组的75.00％,两组比较差异有统计学意义(P＜0.05);实验组治疗后的TNF-α、IL-2低于对照组,IgG、IgM、IgA高于对照组,组间比较差异均有统计学意义(均P＜ 0.05).结论 在血浆置换基础上对重症肌无力患者采用免疫球蛋白治疗,能改善淋巴细胞因子与免疫功能水平,疗效显著,值得临床推广.     

脑内肿瘤坏死因子-α参与高血压发病机制的研究

目的探讨脑内肿瘤坏死因子(TNF)-α通过调节下丘脑室旁核去甲肾上腺素影响高血压大鼠交感神经活动的机制。方法雄性成年SD大鼠,将血管紧张素Ⅱ(ANGⅡ)溶解在生理盐水中由静脉内以10ng.kg-1.min-1持续给药4周制作高血压模型,对照组大鼠给予生理盐水,治疗组通过侧脑室给予TNF-α阻断剂己酮可可碱(PTX)4周,非治疗组给予人工脑脊液(aCSF)4周。大鼠分为高血压治疗组(ANGⅡ+PTX)、高血压非治疗组(ANGⅡ+aCSF)、对照治疗组(生理盐水+PTX)和对照非治疗组(生理盐水+aCSF)。4周后采用高效液相色谱法(HPLC)测量下丘脑室旁核和血浆中去甲肾上腺素水平。结果高血压大鼠下丘脑室旁核和血浆中去甲肾上腺素水平升高(P<0.05),经侧脑室给予PTX4周后可降低下丘脑室旁核和血浆中去甲肾上腺素水平(P<0.05)。结论脑内TNF-α可通过调节下丘脑室旁核去甲肾上腺素水平参与高血压的发病机制,阻断中枢TNF-α合成可在一定程度上降低交感神经兴奋性。     

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.

---

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.