药剂学课程教学改革体会

从理论教学的生动化、实验教学的多样化、新型教学方式的尝试及教师业务水平的提高等四个方面，对药利学教学改革做了全面的总结。其目的在于进一步深化药剂学课程教学改革，提高教学质量。     

两种方法测定灯盏花素经Caco-2细胞模型的转运

目的研究灯盏花素经Caco-2细胞模型转运的特性。方法用培养于Transwell上的Caco-2单层细胞模型研究灯盏花素双向转运;采用生物活性测定及HPLC的方法测定介质中灯盏花素或灯盏乙素的转运量。结果两种方法测定结果显示灯盏花素与灯盏乙素的双向转运Papp具有高度一致性,两者Papp(A-B)均小于1×10-6cm.s-1,流出率ER均大于2。结论采用生物活性法测定灯盏花素Papp具可行性。灯盏花素在Caco-2细胞单层吸收上存在明显外排,这可能是其生物利用度极低的重要原因。     

中药（复方）成分提取动力学数学模型的建立及对六味地黄汤梓醇的验证试验

目的建立封闭体系中药复方成分溶出动力学数学模型，并对六味地黄汤中有效成分梓醇的提取动力学参数进行研究与分析。方法将数学建模方法应用于中药提取过程的研究中，根据提取原理、Fick定律建立中药提取过程的数学模型，对数学模型进行拟合和参数分析。可求得函数表达式，运用该模型研究六味地黄汤中梓醇的动力学参数。结果建立了包舍三项e的指数形式的成分溶出浓度解析厦各参数分析方法。结论封闭可溶中药复方扩散体系的成分溶出符合线性动力学数学模型，各参数可根据溶出浓度表达式关系计算得到。     

Human plasma concentrations of herbicidal carbamate molinate extrapolated from the pharmacokinetics established in in vivo experiments with chimeric mice with humanized liver and physiologically based pharmacokinetic modeling

To predict concentrations in humans of the herbicidal carbamate molinate, used exclusively in rice cultivation, a forward dosimetry approach was carried out using data from lowest-observed-adverse-effect-level doses orally administered to rats, wild type mice, and chimeric mice with humanized liver and from in vitro human and rodent experiments. Human liver microsomes preferentially mediated hydroxylation of molinate, but rat livers additionally produced molinate sulfoxide and an unidentified metabolite. Adjusted animal biomonitoring equivalents for molinate and its primary sulfoxide from animal studies were scaled to human biomonitoring equivalents using known species allometric scaling factors and human metabolic data with a simple physiologically based pharmacokinetic (PBPK) model. The slower disposition of molinate and accumulation of molinate sulfoxide in humans were estimated by modeling after single and multiple doses compared with elimination in rodents. The results from simplified PBPK modeling in combination with chimeric mice with humanized liver suggest that ratios of estimated parameters of molinate sulfoxide exposure in humans to those in rats were three times as many as general safety factor of 10 for species difference in toxicokinetics. Thus, careful regulatory decision is needed when evaluating the human risk resulting from exposure to low doses of molinate and related carbamates based on data obtained from rats.     

甲基莲心碱对2型糖尿病模型大鼠作用的代谢组学研究

目的研究甲基莲心碱对2型糖尿病模型大鼠尿液的代谢产物的影响。方法高脂高糖饲料喂养联合腹腔注射链尿佐菌素造2型糖尿病大鼠模型,糖尿病造模成功后腹腔注射甲基莲心碱20 mg.kg-1.d-1,4周后测大鼠空腹血糖。收集大鼠24 h尿液,样品经处理后进行UPLC/QTOF-MS分析。结果甲基莲心碱处理组大鼠空腹血糖较糖尿病模型组降低(P<0.05)。甲基莲心碱处理糖尿病大鼠后有4种代谢物的含量发生了明显变化,其中二羟延胡索酸(di-hydroxyfumaric acid)下降,前列腺素I2(prostaglandin I2,PGI2)、脂氧素A4(lipoxin A4,LXA4)、脂氧素B4(lipoxinB4,LXB4)升高。结论甲基莲心碱可降低糖尿病大鼠的血糖,改变糖尿病大鼠尿液的代谢产物,其机制可能与其抗氧化应激、抗炎等作用有关。     

二乙基亚硝胺诱导大鼠肝细胞癌系列病理改变及其磁共振成像

目的　探讨新型 1 5T双梯度多通道临床磁共振机对二乙基亚硝胺 (DEN)诱发大鼠肝癌模型肝脏系列病理变化的成像效果 ,并对该技术的价值及前景进行初步探讨。方法　雄性Wistar大鼠 4 0只 ,对其中 30只实施DEN干预 ,另外 10只作为对照 ,根据前期实验的病理结果确定该模型干预期为 14周 ,扫描采样时段在第7～ 2 0周 ,其中 7～ 13周为早期 ,14～ 2 0周为晚期。每 2周随机抽取干预组大鼠 4只、正常组 1～ 2只进行磁共振扫描。采用 3英寸表面线圈 ,并在控制呼吸伪影方面采取了一些措施。于扫描次日处死动物 ,选择性分区取样分析了 72个结节。结合病理检查结果 ,对不同阶段的磁共振显示效果进行分析。结果　实验中有 4只干预组大鼠意外死亡。干预组 2 6只、对照组 10只被完整实施相应的处置。在早、晚期中包含的干预组及对照组大鼠数分别为 14、5只和 12、5只 ,在晚期干预组中 8只有肝癌结节出现 ,其直径可达 2 0mm以上。对这 36只进行的磁共振扫描显示 ,在大鼠的肝癌演进过程中 ,先后有肝组织中毒性炎症、轻度纤维化、肝再生结节 (RN)的形成、肝变异结节 (DN)及癌结节 (HCC)的出现等改变。对 72个不同性质结节的分析显示 ,在T1WI上HCC以低信号为主 (7/11) ,但部分DN也可以呈低信号 (4/ 18) ;T2 WI可以显示更多?     

金钱草及其民间混用品种对高尿酸血症小鼠的效用

目的研究金钱草及其民间混用品种对高尿酸血症小鼠的效用。方法选择化学诱导剂氧嗪酸钾盐作为尿酸酶抑制剂，腹腔注射造成小鼠高尿酸血症模型。将金钱草及其混用品种水提取物灌胃给药，持续4d。采用磷钨酸法测定小鼠血清尿酸水平。结果水提取物能显著地减少高尿酸血症小鼠的血清尿酸水平。结论金钱草及其混用品种水提取物对高尿酸血症小鼠具有降低血清尿酸水平的效用。     

两种国产盐酸西替利嗪片溶出度比较

目的考察盐酸西替利嗪片的体外溶出度,为评价其质量提供参考。方法 采用转篮法测定溶出度,用威布尔(Wcibull)分布模型拟合溶出曲线,并对溶出参数m、T50、Td等采用t检验进行统计分析。结果 两厂家盐酸西替利嗪片的溶出参数无显著性差异(P>0.05)。结论 两国产厂家制剂的溶出度均符合规定。     

沧州市急性阑尾炎“医保”患者药品费用分析

目的:了解沧州市"医保"患者药品使用情况及药品费用控制政策的实施效果。方法:以算术平均数和构成比等指标描述急性阑尾炎患者的药品费用水平,利用秩和检验与多元线性回归模型等方法比较"医保"患者和自费患者的药品费用。结果:"医保"患者药品费用占住院总费用的30%~35%,《沧州市城镇职工基本医疗保险药品目录》以外药品费用占全部药费的9%以下,"医保"患者的药费高于自费患者。结论:沧州市"医保"患者药品费用控制效果较好,但药品费用仍有降低的空间。     

Comparative study of dissolved and nanoparticulate Ag effects on the life cycle of an estuarine meiobenthic copepod,Amphiascus tenuiremis

Many nanotoxicological studies have assessed the acute toxicity of nanoparticles (NPs) at high exposure concentrations. There is a gap in understanding NP chronic environmental effects at lower exposure concentrations. This study reports life-cycle chronic toxicity of sublethal exposures of polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) relative to dissolved silver nitrate (AgNO₃) for the estuarine meiobenthic copepod, Amphiascus tenuiremis, over a range of environmentally relevant concentrations, i.e., 20, 30, 45, and 75?µg-Ag?L^?1. A concentration-dependent increase in mortality of larval nauplii and juvenile copepodites was observed. In both treatment types, significantly higher mortality was observed at 45 and 75?µg-Ag?L^?1 than in controls. In AgNO₃ exposures, fecundity declined sharply (1.8–7 fold) from 30 to 75?µg Ag?L^?1. In contrast, fecundity was not affected by PVP-AgNPs exposures. A Leslie matrix population-growth model predicted sharply 60–86% of decline in overall population sizes and individual life-stage numbers from 30–75?µg-Ag L^?1 as dissolved AgNO₃. In contrast, no population growth suppressions were predicted for any PVP-AgNPs exposures. Slower release of dissolved Ag from PVP-AgNPs and/or reduced Ag uptake in the nanoform may explain these sharp contrasts in copepod response.