人参皂苷Rg1对脑缺血再灌注大鼠nNOS，iNOS表达的影响

【摘要】 目的 探讨人参皂苷Rg1对脑缺血再灌注大鼠脑组织一氧化氮合酶（NOS）表达的影响。方法 将大鼠随机分成假手术组,模型组（脑缺血再灌注损伤组）,人参皂苷Rg1 10,20,40mg/kg组,尼莫地平组（阳性药物对照组）,每组10只。采用大鼠中动脉栓塞法制作大鼠脑缺血再灌注模型,观察大鼠再灌注后神经功能缺损情况,采用比色法检测大鼠nNOS,iNOS和一氧化氮（NO）的含量,应用免疫组化和免疫印迹法检测脑组织缺血再灌注后nNOS,iNOS的表达。结果 （1）人参皂苷Rg1各组大鼠脑缺血后神经功能评分明显低于模型组（p<0.05）;（2）与模型组相比,人参皂苷Rg1各组随浓度增高nNOS含量及表达增高（p<0.05）,iNOS含量及表达明显降低（p<0.05）;（3）免疫组化和免疫印迹的结果也证明这一趋势。结论 人参皂苷Rg1防治大鼠脑缺血再灌注损伤的机制可能与激活nNOS,抑制iNOS有关,且以高剂量效果较好。     

人参皂苷Rg1对大鼠脑缺血再灌注损伤细胞凋亡的影响

目的:研究人参皂苷Rg1对大鼠脑缺血再灌注损伤时细胞凋亡的影响。方法:采用大鼠右侧大脑中动脉阻断(middle cerebral artery occulusion,MCAO)局灶性脑缺血再灌注模型,缺血前给予人参皂苷Rg1 25、501、00 mg.kg-1灌胃,7 d。末次给药1h后制备MCAO模型,缺血2 h,再灌注22 h后,分别用Longa’s法T、TC染色法评价大鼠的神经功能状态及脑梗死面积;用TUNEL法测定缺血再灌后神经细胞凋亡的程度;用Western blot法测定大脑缺血侧脑组织中与凋亡相关基因Caspase-3、Bcl-2的蛋白表达。结果:人参皂苷Rg1(50、100 mg.kg-1)可明显减少MCAO再灌注后脑梗死面积,改善神经功能症状,与模型组比较具有显着性差异(P<0.05或P<0.01);脑缺血2 h再灌22 h后,模型组大鼠缺血侧细胞凋亡程度、Caspase-3蛋白表达明显增加,同时Bcl-2的蛋白表达降低。给予人参皂苷Rg1(50,100mg.kg-1)后,缺血侧细胞凋亡程度、Caspase-3蛋白表达降低,而Bcl-2的蛋白表达增加,与模型组相比具有统计学意义(P<0.01或P<0.05)。结论:人参皂苷Rg1对大鼠脑缺血再灌注损伤引起的细胞凋亡具有明显的保护作用,其机理可能与人参皂苷Rg1影响Caspase-3、Bcl-2的表达有关。     

人参皂苷Rg_1对大鼠脑缺血再灌注损伤及内皮细胞粘附作用的影响(英文)

目的研究抑制白细胞浸润和粘附分子表达是否为人参皂苷Rg1改善大鼠脑缺血再灌注损伤的作用机理之一。方法大鼠给予人参皂苷Rg125,50和100 mg·kg-1ig,7 d。末次给药1 h后采用右侧大脑中动脉阻断制备缺血再灌注模型。缺血2 h,再灌注22 h后,分别用Longa等的计分法和TTC染色法测定大鼠神经功能及脑梗死面积;用伊文思蓝法测定脑缺血2 h再灌注4 h后对血脑屏障的损伤程度。缺血2 h再灌注22 h后测定髓过氧化物酶(MPO)活性,并用蛋白质印迹法测定大脑缺血区粘附分子细胞间粘附分子-1(ICAM-1)和E-选择素的表达。结果缺血再灌注前给予人参皂苷Rg1(50和100 mg·kg-1)可明显改善神经功能症状,减少脑梗死面积,减轻血脑屏障的损伤,降低缺血再灌注所致脑组织内MPO活性及ICAM-1和E-选择素的表达增高。结论人参皂苷Rg1可通过抑制白细胞浸润和粘附分子表达的途径改善大鼠脑缺血再灌注损伤。     

人参皂甙Rb1对大鼠脑缺血再灌注后巢蛋白表达的影响

目的:观察大鼠脑缺血再灌注后脑组织内巢蛋白的表达以及人参皂甙Rb1(Ginsenoside Rb1,GRb1)对神经的保护机制.方法:阻塞大鼠大脑中动脉2h制备脑缺血再灌注模型,大鼠随机分为缺血再灌注组(I/R组)和GRb1给药组(GRb1组).两组按不同的再灌注时间(3h、12h、1d、2d、3d、5d、10d)分为7个亚组,应用免疫组织化学技术检测脑内巢蛋白的表达.结果:与I/R组相比,GRb1能减轻脑组织的病理改变,上调各时间点巢蛋白阳性细胞数.结论:GRb1对脑缺血再灌注损伤有神经保护作用,其机制与上调缺血再灌注大鼠脑内巢蛋白表达水平有关.     

人参皂苷Rg1对抗脑缺血-再灌注大鼠脑组织p—JNK蛋白表达的定量分析

目的：探讨人参皂苷Rg1对脑缺血-再灌注大鼠脑组织p-JNK表达的影响。方法：取健康雄性SD大鼠30只，将其随机分为假手术组，模型组，人参皂苷Rg1 10、20、40mg／kg组，阳性药物对照组，每组5只。采用线栓法制作大脑中动脉栓塞模型。于MCAO术后6h，采用免疫印迹法对CA1区的州NK蛋白表达情况进行定量检测。结果：模型组p-JNK含量最高；假手术组含量最低；Rg1 20、40mg／kg组和阳性药物对照组p-JNK蛋白含量显著降低，与模型组比较有显著性差异（P〈0．05），其中Rg1 40mg／kg组p-JNK蛋白含量最低。结论：人参皂苷Rg1防治大鼠脑缺血-再灌注损伤的机制可能与抑制脑组织p-JNK表达有关，且以高剂量效果较好。     

新生鼠脑缺血预处理后海马CA1区脑源性神经营养因子的表达和意义

目的观察脑缺血预处理对新生Wistar大鼠脑缺血再灌注后海马CAl区脑源性神经营养因子(BDNF)表达的影响和意义。方法通过阻断7日龄新生Wistar大鼠右侧颈总动脉45分钟制备脑缺血模型,设置假手术组、缺血再灌注组和预缺血-缺血再灌注组。采用免疫组化方法和计算机图像分析技术检测3组新生鼠不同时点海马CAl区脑组织BDNF的动态变化及3组光镜下脑组织病理改变。结果(1)脑组织病理改变:预缺血组病理损伤较缺血再灌注组轻。(2)BDNF表达: 预缺血-缺血再灌注组BDNF表达在再灌注后3h开始增高,12h达高峰,24h开始下降,与假手术组和缺血再灌注组比较均有显著性差异(P<0．05),3天降至假手术组水平。结论新生鼠脑缺血预处理早期可诱导海马CAl区BDNF表达和合成增加,对防止再次严重的脑缺血损伤有明显的保护作用, 可能与脑缺血后神经细胞的内源性保护机制有关。     

三七总皂苷对大鼠局灶燃血再灌注损伤TGF－β1表达的影响

目的：观察三七总皂苷（PNs）对局灶性脑缺血再灌注后大鼠脑组织TGF－β1表达的影响,探讨PNS的脑保护机制。方法：采用线栓法制作大鼠大脑中动脉栓塞缺血再灌注损伤模型,将30只成年雄性Sprague－Darley大鼠随机分为假手术组、缺血再灌注组和PNS治疗组,每组10只,各组分别于再灌注24h后做神经功能缺陷评估,并断头取脑,用免疫组织化学法和半定量RT－PCR法检测各组缺血区脑组织TGF－β1表达的变化。结果：与缺血再灌注组相比,PNS治疗组术后大鼠神经功能缺陷评分显著降低,脑组织中TGF－β1的表达水平明显增高。结论：三七总皂苷对脑缺血再灌注大鼠有保护作用,其作用机制可能与促进TGF－β1的表达有关。     

葛根素对大鼠脑缺血/再灌注损伤缺血区细胞粘附分子ICAM-1的影响

目的探讨葛根素对大鼠脑缺血/再灌注损伤缺血区细胞粘附分子ICAM-1的影响。方法采用模拟临床上缺血性卒中的大鼠中脑动脉阻塞局灶性脑缺血/再灌注模型,预先给予葛根素腹腔注射7d后,运用免疫组织化学方法 ,检测大鼠脑缺血/再灌注损伤脑组织中ICAM-1蛋白的表达。结果葛根素能明显降低脑组织缺血区血管内皮细胞ICAM-1蛋白的表达,与模型组相比差异有统计学意义（P〈0.01）。结论葛根素能明显抑制大鼠局灶性脑缺血/再灌注所致炎症反应,对大鼠脑缺血-再灌注造成的脑血管内皮损伤具有明显保护作用。     

缺血后处理对局灶性脑缺血再灌注大鼠Bcl-xl、Bax的影响

目的:观察缺血后处理对局灶性脑缺血再灌注大鼠Bcl-xl、Bax的影响.方法:线栓法建立大鼠大脑中动脉缺血再灌注模型,将成年雄性Wistar大鼠144只,随机分成三组:假手术组、对照组(脑缺血再灌注组)、缺血后处理组.假手术组只进行假手术;对熙组(脑缺血再灌注组)给予90min大脑中动脉缺血(MCAO);缺血后处理组在大脑中动脉缺血90min后,给予灌注30s缺血30s,反复3次.各组分别再灌注12h、24h、48h、72h后测定脑组织Bcl-xl、Bax的表达.结果:局灶性脑缺血后再灌注前给予后处理,缺血后处理组与缺血再灌注组相比,Bcl-xl蛋白的表达明显增加,而Bax蛋白的表达明显减少.结论:脑缺血后处理增加脑缺血再灌注后Bcl-xl蛋白的表达、减少Bax蛋白的表达,从而抑制缺血周围区的细胞凋亡.     

小牛血去蛋白注射液对大鼠脑缺血再灌注损伤的保护作用

目的：研究小牛血去蛋白注射液(depmteinised calf blood iniection，DCBI)对大鼠脑缺血及再灌注损伤的保护作用。方法：采用SD大鼠双侧颈总动脉结扎法制作不完全性脑缺血再灌注模型，观察DCBI对脑缺血再灌注SD大鼠的脑组织水含量，脑组织丙二醛(MDA)含量的影响，并通过光镜观察其病理组织学变化。结果：缺血组与缺血再灌注组脑组织水含量、MDA含量较假手术组明显增高；DCBI组脑组织水含量、MDA含量较缺血组与缺血再灌注组下降。病理组织学检查可见缺血组与假手术组相比大脑皮层细胞出现肿胀改变。缺血再灌注组脑组织水肿加剧，细胞周围呈海绵状。用药组脑细胞仅有轻度肿胀改变。结论：DCBI对大鼠脑缺血及缺血再灌注损伤具有保护作用。     

Role of glutathione in reduction of arsenate and of gamma-glutamyltranspeptidase in disposition of arsenite in rats

Arsenate (AsV), the environmentally prevalent form of arsenic, is converted sequentially in the body to arsenite (AsIII), monomethylarsonic acid (MMAsV), monomethylarsonous acid (MMAsIII), and dimethylarsinic acid (DMAsV) and some trimethylated metabolites. Although the biliary excretion of arsenic in rats is known to be glutathione (GSH)-dependent, involving transport of arsenic-GSH conjugates, the role of GSH in the reduction of AsV to the more toxic AsIII in vivo has not been defined. Therefore, we studied how the fate of AsV is influenced by buthionine sulfoximine (BSO), which depletes GSH in tissues. Control and BSO-treated rats were given AsV (50 micromol/kg, i.v.) and arsenic metabolites in bile, urine, blood and tissues were analysed by HPLC-HG-AFS. BSO increased retention of AsV in blood and tissues and decreased appearance of AsIII in blood, bile (by 96%) and urine (by 63%). The biliary excretion of MMAsIII was also nearly abolished, the appearance of MMAsIII and MMAsV in the blood was delayed and the renal concentrations of these monomethylated arsenicals were decreased by BSO. Interestingly, appearance of DMAsV in blood and urine remained unchanged and the concentrations of this metabolite in the kidneys and muscle were even increased in response to BSO. To test the role of gamma-glutamyltranspeptidase (GGT) in arsenic disposition, the effect of the of the GGT inhibitor acivicin was investigated in rats injected with AsIII (50 micromol/kg, i.v.). Acivicin lowered the hepatic and renal GGT activities and increased the biliary as well as urinary excretion of GSH, but failed to alter the disposition (i.e. blood and tissue concentrations, biliary and urinary excretion) of AsIII and its metabolites. In conclusion, shortage of GSH decreases not only the hepatobiliary transport of arsenic, but also reduction of AsV and the formation of monomethylated arsenic, while not hindering the production of dimethylated arsenic. While GSH plays an important role in the disposition and toxicity of arsenic, GGT, which hydrolyses GSH and GSH conjugates, apparently does not influence the fate of the GSH-reactive trivalent arsenicals in rats.     

微透析取样技术在中药体内分析中的应用研究进展

本文综述了微透析取样技术在中药体内分析中的应用,介绍微透析取样技术的原理、组成、探针类型、特点,重点阐述了微透析取样技术在测定脑、血液、皮肤等组织器官中中药有效成分浓度的应用实例。表明微透析取样技术在中药药效研究中具有广阔的前景。     

Role of desacetylation in the detoxification of cephalothin in renal cells in culture

The toxicity of three cephalosporin antibiotics to rabbit kidney cells in culture was compared to their known nephrotoxic potential in vivo (cephaloridine greater than cefazolin greater than cephalothin). While cephalothin is considered to be a relatively nonnephrotoxic cephalosporin when administered to many species including humans and rabbits, in several in vitro systems involving rabbit renal tissue, cephalothin was comparatively more toxic than anticipated based on in vivo data. Cephalothin is extensively desacetylated in rabbits to a less microbiologically active metabolite, desacetylcephalothin. When a microsomal S9 fraction from rabbit kidney was added to the in vitro assay in cultured rabbit renal cells, cephalothin was desacetylated and its toxicity to kidney cells was reduced. The addition of S9 in vitro provided a toxicity ranking of the cephalosporins that correlated with their known in vivo nephrotoxic potentials (cephaloridine greater than cefazolin greater than cephalothin). The in vitro detoxification of cephalothin by S9 was blocked by the coadministration of the esterase inhibitor, aminocarb. Desacetylcephalothin was relatively nontoxic to rabbit renal tissue in vitro. These results suggest that the desacetylation of cephalothin in vivo represents a previously unrecognized mechanism of detoxification of this cephalosporin antibiotic. Furthermore, this mechanism of detoxification may be applicable to other acetylated cephalosporins.     

2009年某院住院患者抗真菌药用药调查

目的:分析讨论某院抗真菌药使用的合理性,为临床安全有效地使用抗真菌药提供参考。方法:回顾性统计分析某院2009年住院患者抗真菌药用药信息。结果:2009年某院住院患者抗真菌药DDDs排名前3名分别为:氟康唑、制霉菌素和伊曲康唑;使用金额排名前3名分别为:氟康唑、米卡芬净及卡泊芬净;更换一种抗真菌药进行治疗的患者数为176人,在全部患者中占13.4%。结论:应进一步强化用药指征的意识,提高标本送检率,同时改善某些抗真菌用药不合理更换的现象,以避免耐药性发生,从而更好更长远地体现抗真菌药的治疗价值。     

应用PASS系统对我院2008年住院医嘱的分析

目的监测分析2008年我院住院患者用药情况。方法将PASS系统嵌入医生工作站、临床药学工作站等子系统,构建合理用药计算机网络系统,对住院医嘱进行及时监测,将监测结果向医生反馈,并对其进行统计、分析。结果2008年共监测医嘱3 620 241条,不合理医嘱908条,占0.02%。不合理医嘱中,配伍禁忌(381条)占41.96%,用法用量(381条)占41.96%,药物相互作用(108条)占11.89%,儿童用药(38条)占4.19%。经与医生沟通后,更改不合理医嘱856条,占94.27%。结论PASS系统可有效监测医嘱中的不合理用药,通过与医生交流,大大减少药物不良事件的发生,值得临床推广应用,也为临床药师开展工作带来了极大的便利。但PASS系统尚存在局限性,有待进一步完善。     

Kinetics of in vitro metabolism of methoxyphenamine in rats

1. Methoxyphenamine (MP) was metabolized in vitro by rat liver preparations to O-desmethylmethoxyphenamine (O-desmethyl-MP), N-desmethylmethoxyphenamine (N-desmethyl-MP) and 5-hydroxymethoxyphenamine (5-hydroxy-MP). These metabolic pathways were inhibited by SKF 525-A and carbon monoxide, which indicates that these reactions were mediated at least partly by an NADPH-dependent cytochrome P-450 system. 2. Strain differences in the metabolism of this drug in vitro were observed in female Lewis and Dark Agouti (DA) rats, which are proposed models for human debrisoquine phenotypes. Methoxyphenamine O-demethylase and 5-hydroxylase activity in DA rats were lower than those in Lewis rats. 3. The metabolic transformation of methoxyphenamine in vitro to O-desmethyl-MP was inhibited competitively by debrisoquine and sparteine. This indicates that the cytochrome P-450 isoenzyme mediating the metabolism of MP to O-desmethyl-MP is similar to that mediating metabolism of debrisoquine and sparteine. However, no inhibition was observed with methenytoin.     

应用PASS系统分析我院2010年住院医嘱

目的:了解我院2010年住院患者的合理用药情况,探讨如何利用合理用药监测系统( PASS)提高合理用药水平.方法:利用PASS对我院2010年15 966例住院患者的1 184 997条用药医嘱进行监测,以黑色警示医嘱为依据,收集不合理用药信息,并对监测结果进行统计、分析.结果:不合理用药医嘱50 261条,发生率为4.24％.绝对禁止黑色医嘱5441条,主要为药物相互作用(66.54％)、注射液体外配伍(17.86％)、用法用量(15.46％)、儿童警告(1.14％).结论:应用PASS系统能有效监测医嘱中的不合理用药情况,有利于提高临床合理用药水平,但PASS系统尚存在局限性,有待进一步完善.     

Changes in levels of dependency and predictors of mortality in elderly people in institutional care in Dunedin

The 1983 study of dependency of subjects in institutional care in Dunedin was repeated two years later. A significant increase in levels of dependency in residential homes, particularly in the Religious and Welfare sector was found. In 1983 there were 29 high dependency residents and 73 medium dependency residents in residential homes. In 1985 these numbers had increased to 55 and 86 respectively. There was no change in the number of low dependency residents. In 1983, 6 high dependency residents had been admitted to residential home care in the year prior to the study. In 1985 the number of high dependency residents recently admitted had increased to 23. There had also been a significant increase in the dependency of patients in Religious and Welfare continuing care hospitals. Of the 933 subjects in institutional care in 1983 who were able to be followed, 354 (37.9%) died in the following 2 years. Mortality rate was higher for those in hospital care (48.1%) than for those in residential home care (29.6%). Mortality rates were higher in more dependent subjects and this was evident for each measure of dependency.     

基层医院护士在临床合理用药中的作用

目的充分利用护士在医师和患者间的特殊地位和作用,促进基层临床合理用药。方法从护士的工作性质出发,论述护士参与促进合理用药的方便和优势。结果通过实践,护士在促进合理用药中的作用得到有效发挥,基层合理用药环境得到极大改善。结论充分利用护士与医师和患者间的特殊桥梁作用,在基层医院促进合理用药,规范医师用药行为,防止药物滥用,引导患者安全用药,降低药源性疾病。