麦冬水煎剂的遗传毒性研究

目的采用小鼠淋巴瘤细胞试验（MLA）和小鼠骨髓微核试验（MNT）研究麦冬水煎剂的遗传毒性。方法在MLA中,3．36、6．73、13．45、26．90mg（原药材）／mL 4个浓度组在非代谢活化（-S9）和代谢活化（＋S9）条件下与L5178Y细胞作用3h,表达2d,制备突变频率平板并培养12d,计数大、小细胞集落的孔教,计算总突变率（MF）和小集落突变百分率（SC％）;在MNT中,每组10只ICR小鼠,雌雄各半,13．35、6．68、3．34g（原药材）／kg3个剂量组间隔24h灌胃给药2次,制作骨髓涂片,计数每只小鼠2000个嗜多染红细胞中含微核的嗜多染红细胞数,计算每组动物嗜多染红细胞微核率的平均值。结果MLA4个浓度组在＋／-S9条件下诱发的MF呈现剂量相关性增加,与阴性对照组比较有统计学意义（P〈0．01）,SC％与阴性对照组相仿;MNT各剂量组未显示骨髓抑制作用,诱发的微核率与阴性对照组比较未见明显增加。结论麦冬水煎剂在＋／-S9条件下均可诱发L5178Y细胞tk位点突变,提示其可能存在诱变物质;但该供试品对小鼠骨髓细胞染色体无损伤,经体内代谢活化后未显示遗传毒性作用。     

三组中药对耐药菌株的联合作用研究

 目的探讨中药对耐药菌株的联合抑菌作用。方法采用药基法测定了黄芩、大黄、蒲公英、大青叶、鸡屎藤、柳叶白前乙醇提取物对耐药菌株的抑制作用,用棋盘试验法评价了黄芩与大黄、蒲公英与大青叶、鸡屎藤与柳叶白前对耐药菌株的联合作用,用沙门氏菌耐药株人工感染小鼠,观察了鸡屎藤与柳叶白前配伍的体内抗感染效果。结果黄芩、大黄对金黄色葡萄球菌标准株与耐药株的MIC相同,对其他几株耐药菌有较好的抑制作用,蒲公英、大青叶、鸡屎藤、柳叶白前作用较弱,黄芩与大黄存在部分协同或相加作用,蒲公英与大青叶为拮抗作用,鸡屎藤与柳叶白前为部分协同作用并具有较好的体内抗感染作用。结论黄芩与大黄配伍、鸡屎藤与柳叶白前配伍对耐药菌株有较好的抑制作用。     

超声-微波协同萃取法提取杜梨果实多糖

目的提取杜梨果实多糖,并测定其含量。方法采用超声-微波协同萃取法和常规水浴提取杜梨果实多糖,并用蒽酮-硫酸比色法测定多糖含量。结果超声波-微波协同萃取法比较常规水浴法提取杜梨果实多糖效果更好,两种方法提取多糖的含量分别是13.91%和12.74%;葡萄糖浓度在25.15～100.6μg·ml~(-1)范围内呈良好的线性关系,平均回收率为100.5%,RSD1.59%(n=5)。结论超声-微波协同萃取法可作为杜梨果实多糖提取的首选方法,蒽酮-硫酸比色法测定多糖含量的方法准确,重复性好。     

Ames波动试验和GADD45a-GFP GreenScreen两种快速筛选方法评价大黄素和芫花素的遗传毒性

目的 使用Ames波动试验和GADD45a-GFP GreenScreen两种快速筛选方法,对有毒中药芫花和了哥王的主要单体成分大黄素和芫花素的遗传毒性进行评价。方法 （1）Ames波动试验：在非代谢活化（-S9）和代谢活化（+S9）条件下使用鼠伤寒沙门菌TA100开展基于96孔液态培养法的细菌回复性突变试验,大黄素和芫花素（终质量浓度范围均为0.1~10 μg/mL）与菌液充分混合后在37℃下培养72 h。（2）GADD45a GreenScreen高通量筛选试验：在非代谢活化（-S9）和代谢活化条件下（+S9）将表达GADD45a基因的TK细胞（GenM-T01和GenM-C01）与大黄素（0.13~32.0 μg/mL）和芫花素（0.07~16.0 μg/mL）分别作用48 h（-S9）和3 h（+S9）,之后通过酶标仪和流式细胞仪检测绿色荧光蛋白（enhanced green fluorescent protein,EGFP）的荧光强度。结果 有无代谢活化条件下,10 μg/mL大黄素均可诱导TA100的回复性突变率显著性升高（P<0.05、P<0.001）;代谢活化条件下,10 μg/mL芫花素可诱导TA100的回复性突变率显著性升高（P<0.001）,16.0 μg/mL芫花素诱导TK6细胞表达的GADD45a-EGFP荧光强度也超过了遗传毒性阈值（1.3倍）。结论 当前研究提示大黄素和芫花素为可疑遗传毒性,需要开展深入研究明确其遗传毒性及机制。Ames波动试验和GADD45a GreenScreen是良好的高通量筛选备选试验,可极大优化浩繁的药物的毒性筛选工作,尤其适宜诸如中药等成分和配伍复杂的药物。     

药物遗传毒性研究相关要求进展

遗传毒性研究是药物非临床安全性评价的重要内容。人用药品注册技术要求国际协调会(ICH)对药物遗传毒性指导原则进行修订改版,于2008年颁布了S2(R1)人用药物遗传毒性试验和结果分析指导原则,该指导原则对于我国药物遗传毒性研究具有借鉴作用。文中简介了该指导原则修订的科学背景、主要修订内容,并讨论了目前我国药物遗传毒性研究中应关注的几个问题。     

左旋肉碱修饰的壳聚糖-硬脂酸协载槲皮素口服紫杉醇纳米胶束的制备、表征及在体肠循环研究

目的制备左旋肉碱修饰的壳聚糖-硬脂酸(LC-SA/CS-SA)纳米胶束,包载紫杉醇(PTX)且协载槲皮素,考察胶束特性,并以大鼠在体肠循环评估给药系统对PTX口服吸收的促进作用。方法将硬脂酸(SA)通过酰胺化反应接枝于壳聚糖(CS),形成共聚物CS-SA;采用核磁共振H谱、红外光谱鉴定产物结构;以PTX为主药,槲皮素为辅药,采用激光粒径分析、Zeta电位分析和HPLC分析分别考察了胶束的粒径、Zeta电位、载药量、包封率;透射电子显微镜观察胶束形貌;芘荧光探针法测定LC-SA/CS-SA胶束的临界胶束浓度(critical micelle concentration,CMC);透析袋法考察胶束的体外释放行为;大鼠在体肠吸收实验评估载药胶束的促吸收作用。结果红外与核磁结果表明SA通过酰胺键接枝于CS;协载槲皮素的LC-SA/CS-SA载PTX胶束呈类球形,粒径为(148.3±1.7)nm,多分散系数(PDI)为0.16±0.07,Zeta电位为(24.600±0.167)mV,CMC为14.31μg/mL;体外释放结果表明,与市售紫杉醇注射剂相比,协载槲皮素的LC-SA/CS-SA载PT...     

厄洛替尼联合山奈酚诱导卵巢癌细胞凋亡协同作用

目的 探讨厄洛替尼和山奈酚对表皮生长因子受体酪氨酸激酶(EGFR-TPK)的抑制作用,并阐明两者诱导卵巢癌细胞凋亡的协同作用机制。方法 在EGFR-TPK、SKOV-3人卵巢癌细胞株中加入不同浓度(0.1、0.5、1.0、2.5、5.0 mg/mL)山奈酚与厄洛替尼,采用酶联免疫吸附试验(ELISA)测定山奈酚和厄洛替尼对EGFR-TPK的抑制作用,四甲基偶氮唑盐(MTT)法测定山奈酚和厄洛替尼对SKOV-3人卵巢癌细胞株生长的抑制作用和协同效应,酶标仪法检测山奈酚和厄洛替尼对细胞凋亡蛋白caspase-3活性的影响。结果 山奈酚和厄洛替尼对EGFR-TPK的半抑制率(IC₅₀)分别为(2.33±0.32)和(1.75±0.18) mg/mL,差异无统计学意义(P>0.05);与空白对照组比较,0.1、0.5、1.0、2.5、5.0 mg/mL山奈酚和厄洛替尼组肿瘤细胞转移数量均减少,差异均有统计学意义(P<0.05);山奈酚和厄洛替尼协同能力检测结果显示,0.5 mg/mL厄洛替尼与0.5、2.5和5.0 mg/mL山奈酚联合使用对抑制SKOV-3人卵巢癌细胞生长均具有协同效应,2.5和5.0 mg/mL厄洛替尼与0.5、2.5和5.0 mg/mL山奈酚联合使用对抑制SKOV-3人卵巢癌细胞生长均具有加和效应。结论 山奈酚联合厄洛替尼能够诱导SKOV-3人卵巢癌细胞的凋亡,并对SKOV-3人卵巢癌细胞转移起到抑制作用。     

Combined Influence of Lithium Nitrate and Metakaolin on the Reaction of Aggregate with Alkalis

The best known and effective methods for the reduction of the negative effects of an alkali–silica reaction in concrete include the application of mineral additives with an increased aluminium content and reduced share of calcium, as well as chemical admixtures in the form of lithium compounds. Because both aluminium and lithium ions increase the stability of reactive silica in the system with alkalis, it is possible to presume that the application of both corrosion inhibitors together will provide a synergistic effect in the ASR limitation. The paper presents the results of studies on the influence of combined application of metakaolin and lithium nitrate on the course of corrosion caused by the reaction of opal aggregate with alkalis. The potential synergistic effect was studied for the recommended amount of lithium nitrate, i.e., the Li/(Na + K) = 0.74 molar ratio and 5%, 10%, 15%, and 20% of cement mass replacements with metakaolin. The effectiveness of the applied solution was studied by measurements of mortars expansion in an accelerated test, by microstructure observations, and by determination of the ASR gels composition by means of SEM-EDS. The influence of metakaolin and the chemical admixture on the compressive and flexural strengths of mortars after 28 and 90 days of hardening were also analysed. The results of the studies revealed a synergistic effect for mixtures containing metakaolin at 15% and 20% cement replacement and lithium nitrate admixture in alkali–silica reaction expansion tests. It was found that corrosion processes in mortars with 5 and 10% levels of metakaolin became more severe after adding a lithium admixture to mortars with metakaolin only. The obtained results were confirmed by observations of the mortars’ microstructures. There was no synergistic impact of lithium nitrate and metakaolin on compressive strength characteristics. The compressive strength of mortars containing a combination of metakaolin and lithium nitrate decreased both after 28 and after 90 days, compared to mortars with metakaolin alone.     

氟达拉滨的药代动力学及其与阿糖胞苷协同作用的研究进展

氟达拉滨(F-ara-A)作为一种治疗白血病的药物。通过从分子生物学角度研究其作用机制和药代动力学,证明了该药除具有抗肿瘤作用外,还对阿糖胞苷(Ara-C)有增敏作用。在以F-ara-A和Ara-C为基础的临床治疗中,最常见的是FLAG方案,主要用于高危骨髓增生异常综合征及白血病患者。文章综述F-ara-A联合Ara-C在白血病治疗上的研究进展。     

Oral Administration of East Asian Herbal Medicine for Inflammatory Skin Lesions in Plaque Psoriasis: A Systematic Review,Meta-Analysis,and Exploration of Core Herbal Materials

Psoriasis is an inflammatory autoimmune skin disease with various clinical manifestations. The aim of this review was to systematically evaluate the efficacy and safety of oral administration of East Asian herbal medicine (EAHM) for inflammatory skin lesions in psoriasis and to explore core herbal materials for drug discovery. A comprehensive search was conducted in 10 electronic databases for randomized controlled trials from their inception until 29 July 2021. Statistical analysis was performed in R version 4.1.2 and R studio. When heterogeneity in studies was detected, the cause was identified through sensitivity analysis, meta-regression, and subgroup analysis. Methodological quality was independently assessed using the revised tool for risk of bias in randomized trials. A total of 56 trials with 4966 psoriasis patients met the selection criteria. Meta-analysis favored EAHM monotherapy on Psoriasis Area Severity Index (PASI) 70 (RR: 1.2845; 95% CI: 1.906 to 1.3858, p < 0.0001), PASI 60 (RR: 1.1923; 95% CI: 1.1134 to 1.2769, p < 0.0001), continuous PASI score (MD: −2.3386, 95% CI: −3.3068 to −1.3704, p < 0.0001), IL-17, IL-23, TNF-α, and Dermatology Life Quality Index. Patients treated with EAHM monotherapy had significantly reduced adverse events incidence rate. In addition, based on additional examination of the herb data included in this meta-analysis, 16 core materials were identified. They are utilized in close proximity to one another, and all have anti-inflammatory properties. The findings in this study support that oral EAHM monotherapy may be beneficial for inflammatory skin lesions in psoriasis. Meanwhile, the identified core materials are expected to be utilized as useful drug candidate hypotheses through follow-up studies on individual pharmacological activities and synergistic effects.