呋喃唑酮促睾丸细胞凋亡作用

目的探讨呋喃唑酮(NFZ)诱导大鼠睾丸细胞凋亡的作用,为指导临床药物及禽畜药物的使用提供一定的理论依据。方法采用免疫组化、细胞培养、亚细胞器分离、无细胞体系及免疫沉淀技术,观察睾丸细胞在NFZ作用下形态变化;检查睾丸细胞及其无细胞系统在NFZ作用后的DNA梯状电泳图谱以及与凋亡相关的Bcl-2、caspase-3等因子表达。结果睾丸细胞在NFZ作用下,形态变化具有明显的凋亡特征。DNA电泳出现梯状电泳带,即DNA片段化。分析与凋亡相关的因子表达,均符合细胞程序死亡的规律。结论呋喃唑酮可促进精子细胞凋亡。     

二乙胺在呋喃唑酮含量测定中应用的研究

本文概述二乙胺在呋喃唑酮含量测定中应用的研究。以二乙胺取代吡啶或 N,N-二甲基甲酰胺,消除了不利因素。该法的测定精度和准确度完全能满足分析要求,且溶剂体系的稳定性尚可。     

氟吗啉原药对Wistar大鼠致畸性毒性研究

以Wistar大鼠为实验动物,进行了氟吗啉(SYP-L190)原药对该品系大鼠的致畸性毒性研究.设计剂量为30mg/kg、132mg/kg、300mg/kg3个剂量组和1个阴性对照组(食用油)及1个阳性对照组(敌枯双),对妊娠大鼠于第6～15天染毒.在动物怀孕第20天将妊娠大鼠脱颈椎处死,取出胎鼠进行检查.结果表明:在本试验条件下,以300mg/kg剂量经口投与wistar妊娠大鼠,可产生较明显的胚胎毒性作用,但没有出现致畸作用.     

雷贝拉唑、呋喃唑酮、阿莫西林三联治疗幽门螺杆菌相关消化性溃疡的临床观察

目的观察雷贝拉唑、呋喃唑酮、阿莫西林三联疗法对幽门螺杆菌相关消化性溃疡的疗效。方法63例幽门螺杆菌相关消化性溃疡患者分为两组,对照组(31例)给予奥美拉唑、克拉霉素、阿莫西林三联治疗1周后,继续单用奥美拉唑3周。实验组(32例)给予雷贝拉唑、呋喃唑酮、阿莫西林三联治疗1周。治疗后不同时间点比较两组症状改善情况;治疗结束4周后,观察幽门螺杆菌清除及溃疡治愈情况。结果治疗1周后,实验组症状缓解率明显高于对照组,有显著差异性(P<0.05);而其余时间点两组无明显区别。治疗结束4周后,实验组在幽门螺杆菌清除率及溃疡治愈率方面与对照组无显著差异性(P>0.05)。结论雷贝拉唑、呋喃唑酮、阿莫西林三联治疗幽门螺杆菌相关消化性溃疡,具有症状改善迅速、治疗周期短、幽门螺杆菌根除率、溃疡治愈率与传统三联疗法相似的优点。     

呋喃唑酮代谢物单克隆抗体及其新型免疫层析检测试纸条的制备

目的制备呋喃唑酮代谢物AOZ单克隆抗体及其胶体金与荧光淬灭免疫层析试纸条。方法将AOZ衍生成CPAOZ后,与载体蛋白BSA偶联,制备完全抗原CPAOZ-BSA,经皮下多点注射免疫BALB/c小鼠,共5次,取小鼠脾细胞与SP2/0细胞融合,获得稳定分泌特异性抗体的杂交瘤细胞株。利用获得的抗CPAOZ单克隆抗体制备胶体金及荧光淬灭免疫层析试纸条,并对试纸条的灵敏度及特异性进行验证。结果制备的完全抗原经紫外扫描鉴定偶联成功。共获得3株能稳定分泌抗CPAOZ单克隆抗体的杂交瘤细胞株,其中效价和特异性最好的1株2H11针对CPAOZ的50%抑制质量浓度(IC50)为0.88 ppb。以该抗体制备的胶体金及荧光淬灭免疫层析试纸条的最低检测限分别为7.5和0.062 5 ppb;两种试纸条与其他3种硝基呋喃类代谢物CPAMOZ、CPAHD、CPSEM均不存在交叉反应。结论成功制备了抗CPAOZ单抗及其胶体金免疫层析和荧光淬灭免疫层析试纸条,两种试纸条均具有较高的灵敏度和较强的特异性,其中荧光淬灭免疫层析试纸条的灵敏度较胶体金免疫层析试纸条高约100倍,具有良好的应用前景。     

95．7％高效氟吡甲禾灵原药对Wistar大鼠的13周饲喂毒性

用95.7%高效氟吡甲禾灵原药对Wistar大鼠进行了13周喂饲毒性实验,实验设0、40(低)、200(中)、1000(高)mg/kg饲料4个剂量组,每组雌、雄鼠均为10只.实验结果表明:雄鼠中、高剂量组和雌鼠高剂量组的体重增长受到抑制;雄鼠低、中、高剂量组肝脏、睾丸的相对重最增高,雌鼠中、高剂量组动物肝脏相对重量增高;雄鼠低、中、高剂量组均出现睾丸无精子或精子形成低下、单个肝细胞坏死、小叶中心区肝细胞肿大等症状,而雌鼠中、高剂量组观察到单个肝细胞坏死,小叶中心区肝细胞肿大等症状;雄鼠低、中、高剂量组和雌鼠中、高剂量组动物碱性磷酸酶(ALP)水平增高,雌鼠和雄鼠的中、高剂量组动物丙氨酸氰基转氨酶(ALT)水平均增高,雄鼠高剂毋组总胆同醇水平增高,与对照相比差异显著.根据实验结果,在实验条件下,95.7%高效氟吡甲禾灵原药最大无作用剂量为雄性小于(3.01±0.31)mg/kg·d),雌性(3.10±0.18)mg/(kg·d),靶器官为肝脏和雄性动物的睾丸.     

硒化卡拉胶寡糖的制备及其抑制血管生成作用研究

在酸性条件下,利用亚硒酸钠和卡拉胶反应制备硒化卡拉胶寡糖,硒含量达到30μg·mg-1。以鸡胚尿囊膜为模型研究硒化卡拉胶寡糖抑制血管生成作用,通过血管内皮细胞划痕实验和分化成管实验研究硒化卡拉胶寡糖抑制人脐静脉血管内皮细胞迁移和分化成管作用。结果发现,硒化卡拉胶寡糖具有抑制血管生成的作用,其抑制血管生成作用与其抑制血管内皮细胞迁移和分化成管作用相关,而且在50~200μg·mL-1的范围内抑制作用与浓度正相关。     

溶栓治疗大鼠急性脑梗死的实验研究

目的采用大鼠大脑中动脉梗死(MCAO)模型,评价不同时间窗尿激酶溶栓疗法疗效的差异。方法自体血栓法制作大鼠MCAO模型,90只大鼠随机分为6组。在栓塞后2h、4h、6h分别给予尿激酶及生理盐水。在溶栓前后2h、4h、6h各时点分别记录神经功能评分,TTC染色,计算梗死体积,光镜观察。结果神经功能评分,仅2h治疗组有显著性差异;脑梗死体积,2h和4h治疗组有显著性差异;光镜发现2h治疗组病理改变较轻。结论脑梗死后2h尿激酶治疗可减小梗死体积、改善神经功能。光镜观察发现病理改变最轻。     

碳酸二甲酯羰基化合成呋喃唑酮

介绍了所开发的呋喃唑酮的碳酸二甲酯羰基化合成清洁工艺,并叙述了对催化剂,原料配比,反应精馏,反应时间以及溶剂等多种因素对过程影响的考察结果,从而确立了较佳的工艺条件。     

溴氟菊酯的大鼠两代繁殖毒性实验

为保证溴氟菊酯原油的安全使用,选用Wistar大鼠进行两代繁殖毒性的实验。溴氟菊酯原油在各喂饲饲料中的含量分别为0、20、200、1000mg/kg。试验中观察了亲代及子代实验动物的体重、行为表现、血液常规、血清生化、病理学检查以及幼仔的身长、尾长、窝重等指标,并计算繁殖指数指标。结果显示,在本试验条件下溴氟菊酯原油对大鼠的最大无繁殖毒性剂量分别为雄性大鼠1.87mg/kgbw·d、雌性大鼠1.97mg/kgbw·d。     

神经生长因子对大鼠视网膜缺血-再灌注损伤的保护作用

用眼内高压法造成大鼠视网膜缺血45min,然后回复常压,造成缺血-再灌注损伤。采用符合临床给药途径的眼球分注射法,小鼠颌下腺神经生长因子（NGF）250、500、1000BU／眼,于缺血损伤前及其后球旁注射,每天1次,连续4天,第10天取材病检。观察到NGF500、1000BU／眼可减轻视网膜缺血-再灌注损伤,使神经节细胞存活率增加,视网膜全层及内核层萎缩减轻。提示NGF球旁注射可扩散到视网膜,对视网膜缺血-再灌注损伤产生保护作用。     

慢性粒细胞白血病树突状细胞对T细胞增殖作用的研究

目的　体外诱导慢性粒细胞白血病 (CML)患者外周血单个核细胞 (PBMCs)为树突状细胞 (DCs) ,并对其形态、表型及对T细胞刺激增殖作用进行研究。方法　利用GM CSF、IL 4、TNF α体外定向诱导生成树突状细胞 ,对所诱生的细胞进行细胞表型及形态检测 ,用D FISH方法检测所诱生DCs的白血病源性 ,应用MTT法检测所诱生的DCs刺激T细胞增殖的能力。结果　CML患者PBMCs在体外可诱导生成bcr/abl融合基因阳性的DCs(CMLDCs)。CMLDCs对自体T细胞有明显刺激增殖作用 ,而CML细胞无此作用。CMLDCs刺激同一异体T细胞增殖能力弱于正常DCs,但当培养体系中加入 30 0U/ml干扰素 α(IFN α)时可使其刺激能力接近正常DCs。结论　CMLDCs具有刺激自体及异体T细胞增殖的能力 ,但对异体T细胞的刺激作用弱于正常DCs,IFN α可提高CMLDCs刺激T细胞增殖能力     

Effect of Glucocorticoid Receptor Antagonism on Alcohol Self-Administration in Genetically-Selected Marchigian Sardinian Alcohol-Preferring and Non-Preferring Wistar Rats

Alcoholism is a chronically relapsing disorder characterized by high alcohol intake and a negative emotional state during abstinence, which contributes to excessive drinking and susceptibility to relapse. Stress, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and alterations in glucocorticoid receptor (GR) function have been linked to transition from recreational consumption to alcohol use disorder (AUD). Here, we investigated the effect of pharmacological antagonisms of GR on alcohol self-administration (SA) using male and female Wistar and Marchigian Sardinian alcohol-preferring (msP) rats, a rodent line genetically selected for excessive alcohol drinking and highly sensitive to stress. Animals were trained to self-administer 10% (v/v) alcohol. Once a stable alcohol SA baseline was reached, we tested the effect of the GR antagonists mifepristone (0.0, 10, 30 and 60 mg/kg; i.p.) and CORT113176 (0.0, 10, 30 and 60 mg/kg) on alcohol SA. To evaluate whether the effects of the two compounds were specific for alcohol, the two drugs were tested on a similar saccharin SA regimen. Finally, basal blood corticosterone (CORT) levels before and after alcohol SA were determined. Systemic injection with mifepristone dose-dependently reduced alcohol SA in male and female Wistars but not in msPs. Administration of CORT113176 decreased alcohol SA in male and female Wistars as well as in female msPs but not in male msP rats. At the highest dose, mifepristone also reduced saccharin SA in male Wistars and female msPs, suggesting the occurrence of some nonspecific effects at 60 mg/kg of the drug. Similarly, the highest dose of CORT113176 (60 mg/kg) decreased saccharin intake in male Wistars. Analysis of CORT levels revealed that females of both rat lines had higher blood levels of CORT compared to males. Alcohol consumption reduced CORT in females but not in males. Overall, these findings indicate that selective blockade of GR selectively reduces alcohol SA, and genetically selected msP rats are less sensitive to this pharmacological manipulation compared to heterogeneous Wistars. Moreover, results suggest sex differences in response to GR antagonism and the ability of alcohol to regulate GR transmission.     

Inducing Effect of Clofibric Acid on Stearoyl‐CoA Desaturase in Intestinal Mucosa of Rats

Fibrates have been reported to elevate the hepatic proportion of oleic acid (18:1n‐9) through inducing stearoyl‐CoA desaturase (SCD). Despite abundant studies on the regulation of SCD in the liver, little is known about this issue in the small intestine. The present study aimed to investigate the effect of clofibric acid on the fatty acid profile, particularly monounsaturated fatty acids (MUFA), and the SCD expression in intestinal mucosa. Treatment of rats with a diet containing 0.5 % (w/w) clofibric acid for 7 days changed the MUFA profile of total lipids in intestinal mucosa; the proportion of 18:1n‐9 was significantly increased, whereas those of palmitoleic (16:1n‐7) and cis‐vaccenic (18:1n‐7) acids were not changed. Upon the treatment with clofibric acid, SCD was induced and the gene expression of SCD1, SCD2, and fatty acid elongase (Elovl) 6 was up‐regulated, but that of Elovl5 was unaffected. Fat‐free diet feeding for 28 days increased the proportions of 16:1n‐7 and 18:1n‐7, but did not effectively change that of 18:1n‐9, in intestinal mucosa. Fat‐free diet feeding up‐regulated the gene expression of SCD1, but not that of SCD2, Elovl6, or Elovl5. These results indicate that intestinal mucosa significantly changes its MUFA profile in response to challenges by clofibric acid and a fat‐free diet and suggest that up‐regulation of the gene expression of SCD along with Elovl6 is indispensable to elevate the proportion of 18:1n‐9 in intestinal mucosa.     

Matrine Exerts a Strong Anti-Arthritic Effect on Type II Collagen-Induced Arthritis in Rats by Inhibiting Inflammatory Responses

To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA) in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days). Subsequently, blood was collected to determine serum levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-IκB, IκB, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-κB pathway.     

The Effect of Osteoblast Isolation Methods from Adult Rats on Osteoclastogenesis in Co-Cultures

Co-cultures of osteoblasts and osteoclasts are on the rise because they enable a more complex study. Diseases such as osteoporosis are related to a higher age. Thus, cell isolation from adult individuals is necessary. Osteoblasts can be isolated from the rat femur by three methods: explant culture, explant culture with enzymatic pre-treatment, or enzymatic treatment. The isolation methods yield different populations of osteoblasts which, in a co-culture with peripheral blood mononuclear cells, might result in differences in osteoclastogenesis. Therefore, we examined the differences in osteogenic markers, cell proliferation, and the metabolic activity of isolated osteoblast-like cells in a growth and differentiation medium. We then evaluated the effect of the isolated populations of osteoblast-like cells on osteoclastogenesis in a subsequent co-culture by evaluating osteoclast markers, counting formed osteoclast-like cells, and analyzing their area and number of nuclei. Co-cultures were performed in the presence or absence of osteoclastogenic growth factors, M-CSF and RANKL. It was discovered that enzymatic isolation is not feasible in adult rats, but explant culture and explant culture with enzymatic pre-treatment were both successful. Explant culture with enzymatic pre-treatment yielded cells with a higher proliferation than explant culture in a growth medium. The differentiation medium reduced differences in proliferation during the culture. Some differences in metabolic activity and ALP activity were also found between the osteoblast-like cells isolated by explant culture or by explant culture with enzymatic pre-treatment, but only on some days of cultivation. According to microscopy, the presence of exogenous growth factors supporting osteoclastogenesis in co-cultures was necessary for the formation of osteoclast-like cells. In this case, the formation of a higher number of osteoclast-like cells with a larger area was observed in the co-culture with osteoblast-like cells isolated by explant culture compared to the explant culture with enzymatic pre-treatment. Apart from this observation, no differences in osteoclast markers were noted between the co-cultures with osteoblast-like cells isolated by explant culture and the explant culture with enzymatic pre-treatment. The TRAP and CA II activity was higher in the co-cultures with exogenous growth than that in the co-cultures without exogenous growth factors on day 7, but the opposite was true on day 14. To conclude, explant culture and explant culture with enzymatic pre-treatment are both suitable methods to yield osteoblast-like cells from adult rats capable of promoting osteoclastogenesis in a direct co-culture with peripheral blood mononuclear cells. Explant culture with enzymatic pre-treatment yielded cells with a higher proliferation. The explant culture yielded osteoblast-like cells which induced the formation of a higher number of osteoclast-like cells with a larger area compared to the explant culture with enzymatic pre-treatment when cultured with exogenous M-CSF and RANKL.     

乙烯装置减缓结焦结垢新技术及其应用评述

介绍了乙烯装置减缓结焦结垢新技术，如设备结构改进、表面涂层、高效阻聚剂、在线吹扫等，讨论了这些新技术应用效果，提出了综合应用新技术实现乙烯装置长周期运转的建议。