朱砂对大鼠的肝肾毒性研究

目的:研究朱砂的肝、肾毒性特点,提出朱砂安全用药剂量和用药时间建议,为朱砂的临床安全用药提供科学依据.方法:小鼠单次灌胃给药,测定最大耐受量.采用SD大鼠随机分为对照组和朱砂0.025,0.05,0.1,0.4,0.8 g·kg-1·d~(-1)(相当于《中国药典》剂量高限的1/2,1,2,8,16倍)剂量组.各剂量组均每日灌胃给药1次,连续3个月,于给药后1,2,3个月和停药1个月,测定尿液定性、血常规以及血清生化指标,并观察肝、肾、心、脑等主要脏器的组织形态学变化,确定无明显不良作用水平(NOAEL).结果:朱砂在HgS为98%、可溶性汞为21.5μg·g~(-1)情况下,给小鼠单次灌胃给药最大耐受量达到24g·kg~(-1)(等于摄入可溶性汞516μg·kg~(-1)),相当于人日用量约3 000倍,未见明显毒性反应.朱砂超过一定剂量用药达到1个月以上,肾脏和肝脏均可见与朱砂毒性有关的病理改变,其中,肾脏对朱砂更为敏感.大鼠灌胃朱砂1个月和3个月的无明显毒性剂量分别为0.1,0.05 g·kg~(-1)·d~(-1)(累积摄入可溶性汞64.5,96μg·kg~(-1)).按照安全系数为60计算出人服用朱砂的日允许摄入量(acceptable daily intake,ADI)约为0.000 9～0.001 7 g·kg~(-1)·d~(-1),相当于60 kg人日用剂量为0.05～0.1 g.结论:反复使用朱砂时,建议在可溶性汞含量≤21 μg·g~(-1)的条件下,朱砂的用药剂量不宜超过0.05～0.1 g,用药时间不宜超过2周.     

微波消解-ICP-OES法检测湘产朱砂中重金属的含量

目的建立微波消解-电感耦合等离子体原子发射光谱法（ICP-OES）检测湘产朱砂中Cd、Cr、Cu、Pb的含量,为矿物药的重金属检测提供参考。方法通过对比湿法消解,优选出微波消解作为朱砂样品的前处理方法,结合电感耦合等离子体发射光谱法（ICP-OES）的分析手段,对湖南产的11批朱砂样品中重金属含量进行检测。结果方法的线性相关系数为0.999 8～1.000 0,检出限为0.18～5.54μg·L^-1,RSD为0.55%～3.20%,回收率为84.30%～108.36%,经方法学验证适合同时测定朱砂中Cd、Cr、Cu、Pb的含量。结论该方法简便、准确,可同时检测朱砂中重金属Cd、Cr、Cu、Pb的含量。     

Behavior and single gene substitution inDrosophila melanogaster. I. Mating and courtship differences withw,cn, andbw Loci

The effect of single allele substitutions into an isogenic background in Oregon-R inbred lines of Drosophila melanogaster on courtship and mating patterns has been studied. A comparison has been made between the white locusw, w ^co ,w ^e , the wild typew ⁺ ,cn, bw, andcn bw to test the effect of eye pigmentation in influencing courtship and mating patterns. It was found thatw, w ^e ,w ^co ,cn, andbw females were more successful in mating than were wild-type andcn bw females,cn bw females being less successful than wild-type females. Also,w andcn bw males were equally successful in mating but less successful than wild-type males during the 20-min test period. The mutant males performed as well as the wild-type after courtship was initiated. The behavioral parameters measured were (1) courtship latency, the time from exposure of male to female until orientation; (2) mating speed, the time from beginning of orientation of male to female until successful copulation; and (3) copulation time.Contribution No. 525 from the Department of Biological Sciences, Northern Illinois University, DeKalb, Illinois.     

Chemical form of metals in traditional medicines underlines potential toxicity in cell cultures

Ethnopharmacological relevance

Mercury (Hg) and arsenic (As) are frequently found in traditional medicines as sulfides, such as cinnabar (HgS) and realgar (As₄S₄). There is a general perception that any medicinal use of such metal-containing remedies is unacceptable. An opposing opinion is that different chemical forms of arsenic and mercury have different toxic potentials.

Aim of the study

To clarify this question, cinnabar, realgar, and cinnabar- and realgar-containing traditional medicine An-Gong-Niu-HuangWan (AGNH), were compared to well-known mercurials (HgS, HgCl₂ and MeHg) and arsenicals (As₂S₂, As₂O₃, NaAsO₂, and Na₂HAsO₄) for their cytotoxicity in human and rodent cell lines.

Materials and method

Cultured cells derived from target organs such as brain (HAPI) and liver (Hep3B, HepG2 and TRL1215) were treated with chemicals for 48 h and cytotoxicity was determined by the MTS assay.

Results

MeHg was most toxic with LC₅₀ of 4-20 μM, followed by NaAsO₂ (LC₅₀, 25-250 μM) and HgCl₂ (LC_50, 50-100 μM), Na₂HAsO₄(LC₅₀, 60-400 μM), As₂O₃(LC₅₀, 30-900 μM), and As₂S₂ (LC₅₀, 100-500 μM). In comparison, the LC₅₀ of realgar ranged from 250 to1500 μM; whereas cinnabar or HgS were approximately 20,000 μM and the toxicity of AGNH was in the range of 1500-8000 μM. Approximately 5000-fold differences exist between MeHg and HgS, and over 10-fold differences exist between NaAsO₂ and As₄S₄.

Conclusions

Chemical forms of metals are important factor in determining their toxicity in traditional medicines, both cinnabar and realgar are much less toxic than well-known mercurial and arsenicals.     

朱砂中HgS含量、形态和晶形研究

目的:对朱砂中HgS含量、形态和晶形进行研究,并与伪品朱砂进行比较.方法:采用性状、显微、理化鉴别的方法,确立朱砂鉴别特征;采用X-射线衍射和电镜分析法,对朱砂的粒径大小、形貌和晶型进行表征;采用容量分析测定朱砂中HgS含量.结果:可通过性状、显微、理化特征等的差异鉴别朱砂及其伪品;朱砂有两种变体(α-HgS和β-HgS),不同产地的朱砂样品具有相对稳定的X-射线单晶衍射特征.结论:朱砂中HgS含量、形态和晶形是影响朱砂药材质量的重要因素.     

传统中药朱砂应用概况及其安全性

朱砂作为传统中药已有2000多年历史，1963年至2005年《中国药典》各版均予收载。朱砂主要用于治疗心悸易惊、失眠多梦、癫痫发狂、小儿惊风、视物昏花、口疮、喉痹和疮疡肿毒等。近年研究证明，朱砂具有镇静催眠、抗惊厥、抗心律失常、抗菌、抗寄生虫等作用。《中国药典》规定朱砂的日用剂量为0．1～0．5g。但据不完全统计，目前约有170多种朱砂制剂中的朱砂用量超过上述剂量。朱砂的主要成分为硫化汞（HgS），其毒性很小；但大剂量或长期服用可引起急、慢性中毒，这可能与朱砂含有游离汞和可溶性汞盐有关。朱砂所致中毒表现为口腔黏膜溃疡、急性胃肠炎、神经和肾功能损害、循环衰竭，甚至死亡。作者认为对朱砂临床应用的利弊有待对朱砂及其制剂的有效性和安全性作深入研究的基础上再作科学评价。     

丹酚酸B预处理的心脏微血管内皮细胞延迟保护作用研究

目的探讨丹酚酸B通过保护心脏微血管内皮细胞(CMEC)抗心肌缺氧损伤作用机制.方法基于缺血预适应延迟保护机制,通过缺氧/复氧的CMEC损伤模型,观察丹酚酸B预处理的CMEC保护作用.结果丹酚酸B预处理与缺氧预处理作用相似,均可提高细胞存活率和SOD活性,降低LDH、NO水平.结论丹酚酸B预处理可激活CMEC内源性延迟保护机制,发挥了拮抗心肌缺血缺氧损伤效应.     

朱砂溶出的体外研究

目的：研究胃肠道中存在的各种化学因素（酸度，蛋白质，氨基酸，离子强度，Na2S）对朱砂溶出的影响。方法：分别使用紫外可见分光光度仪、纳米粒度仪、质谱仪对朱砂在不同化学体系溶出液中汞的浓度、溶出液的粒度分布以及溶出物的组成进行分析。结果：朱砂主要不以纳米颗粒形式溶出，含巯基的氨基酸对朱砂的促溶作用有限，而Na2S对朱砂中汞溶出量的影响显著高于其他，pH对朱砂中汞的溶出量也有较大的影响。结论：推测朱砂在胃肠道中的溶出物可能主要为汞的各种含硫配合物。     

科学评价含雄黄、朱砂中成药的安全性

雄黄和朱砂与其他中药配伍应用于临床已有上千年历史,但由于雄黄含砷,朱砂含汞,其安全性近年来引起了越来越多的关注,加之现有对含雄黄和朱砂中药的金属含量仍以总砷和总汞为标准进行评价,所以含雄黄和朱砂的中成药因砷、汞超标引起了民众的广泛忧虑,不但治疗作用受质疑,毒性作用被夸大,而且使其出口受限制,声誉受影响.因此,含雄黄、朱砂中成药安全性评价就尤为重要,本文就含雄黄和朱砂中成药的毒理研究进展作一综述.     

含与不含朱砂的万氏牛黄清心丸对高热惊厥大鼠模型的影响

目的 比较含与不含朱砂的万氏牛黄清心丸的抗惊厥作用.方法 制备大鼠高热惊厥模型,记录模型大鼠给予万氏牛黄清心丸(1号方)、去除朱砂的万氏牛黄清心丸(2号方)、酸枣仁替代朱砂的万氏牛黄清心丸(3号方)后的惊厥潜伏期;取大鼠海马切片,HE染色和尼氏染色,观察海马CA1、CA2、CA3区神经元形态并海马神经元计数;以安宫牛黄丸作为阳性对照.结果 随着惊厥诱导次数的增加,各组动物惊厥潜伏期均延长,与模型组比较,各给药组不同程度地延长惊厥潜伏期;与1号方比较,2号方及3号方各剂量组大鼠惊厥潜伏期均无明显差异;模型大鼠海马各区神经元形态发生明显的病理改变,1号方能明显增加模型大鼠海马神经元数目,与模型组比较差异非常显著;2号方和3号方对海马神经元的影响与1号方无明显差异.结论 1号方、2号方和3号方均有明显的抗惊厥作用,三者作用无明显差异.