雄黄对乳腺癌MCF-7/ADM细胞多药耐药的逆转及机制研究

目的　探讨中药雄黄对乳腺癌多药耐药细胞系 (MCF 7/ADM )的逆转作用及可能的逆转机制。方法　药物敏感试验采用四氮唑蓝 (MTT)比色法 ,细胞内药物浓度测定采用荧光分光光度法 ;基因表达水平检测采用RT -PCR法。结果　雄黄在 0～ 2 5 μg/ml浓度范围内对MCF 7/ADM细胞未见明显毒副作用 ;15 μg/ml、2 5 μg/ml雄黄逆转倍数分别为 2 0倍和 2 8倍 ,并能明显抑制mdr 1基因的转录水平。 结论　雄黄可以逆转MCF 7/ADM细胞的多药耐药性 ,并呈剂量依赖性 ;可能的逆转机制为下调mdr 1基因的表达     

雄黄诱导K562／ADM细胞凋亡的研究

探讨雄黄诱导多药耐药细胞Ｋ５６２／ＡＤＭ细胞凋亡的能力,并初步探讨其分子机制,方法：采用荧光标记形态学观察,流式细胞仪进行ＤＮＡ分析及测定细胞表面ｐ－ｇｐ的表达。结果显示：雄黄能明显诱导Ｋ５６２／ＡＤＭ细胞凋亡,且在４８ｈ后ｐ－ｇｐ的表达下调。     

雄黄与毒砂及其升华物的鉴别研究

对雄黄与毒砂及其升华物的形性及理化性质进行了比较鉴别,结果表明:雄黄和毒砂在性状及理化性质上均有显著差异,特别是二者升华物的不同必将直接影响剧毒中药信石的质量。     

Relation of Blood Arsenic Concentration with Effect and Safety of Arsenic-Containing Qinghuang Powder (青黄散) in Patients with Myelodysplastic Syndrome

Objective: To investigate the relation of blood arsenic concentration(BAC) with clinical effect and safety of arsenic-containing Qinghuang Powder(青黄散, QHP) in patients with myelodysplastic syndrome(MDS). Methods: Totally 163 patients with MDS were orally treated with QHP for 2 courses of treatment, 3 months as 1 course. The BACs of patients were detected by atomic fluorescence spectrophotometry at 1, 3, and 6 months during the treatment, and the effective rate, hematological improvement and safety in patients after treatment with QHP were analyzed. Results: After 2 courses of treatment, the total effective rate was 89.6%(146/163), with 31.3%(51/163) of hematological improvement and 58.3%(95/163) of stable disease. The hemoglobin increased from 73.48±19.30 g/L to 80.39±26.56 g/L(P0.05), the absolute neutrophil count increased from 0.81±0.48×10~9/L to 1.08±0.62×10~9/L(P0.05), and no significant changes were observed in platelet counts(P0.05). Among 46 patients previously depended on blood transfusion, 28.3%(13/46) completely got rid of blood transfusion and 21.7%(10/46) reduced the volume of blood transfusion by more than 50% after treatment. The BACs were significantly increased in patients treated for 1 month with 32.17±18.04 μg/L(P0.05), 3 months with 33.56±15.28 μg/L(P0.05), and 6 months with 36.78±11.92 μg/L(P0.05), respectively, as compared with those before treatment(4.08±2.11 μg/L). There were no significant differences of BACs among the patients treated for 1, 3 and 6 months(P0.05). The adverse reactions of digestive tract during the treatment were mild abdominal pain and diarrhea in 14 cases(8.6%), and no patients discontinued the treatment. The BACs of patients with gastrointestinal adverse reactions were significantly lower than those without gastrointestinal adverse reactions(22.39±10.38 vs. 37.89±11.84, μg/L, P0.05). The BACs of patients with clinical effect were significantly higher than those failed to treatment(40.41±11.69 vs. 23.84±12.03, μg/L, P0.05). Conclusion: QHP was effective and safe in the treatment of patients with MDS and the effect was associated with BACs of patients.     

雄黄对细粒棘球蚴原头节体外生长及抗氧化酶活性的影响

目的初步探讨雄黄对体外细粒棘球蚴原头节生长及抗氧化酶的影响。方法在体外培养的基础上,将不同浓度雄黄分别作用细粒棘球蚴原头节2 d,光镜下观察原头节活力及形态变化;扫描电镜(SEM)和透射电镜(TEM)观察原头节表面及内部超微结构改变;采用ELISA法测定SOD、ROS、HO-1和NQO-1表达情况;采用Caspase-3试剂盒检测原头节Caspase-3酶活性。结果250、500、1000、2000μmol/L雄黄体外作用于细粒棘球蚴原头节均能抑制其生长,雄黄作用2 d后光镜下观察原头节形态结构均发生改变,虫体萎缩,伊红染色呈红色(正常虫体为透明无色);SEM下观察原头节虫体皱缩,原头节正常形态被破坏;TEM下观察原头节内部微绒毛减少,合胞体带变薄、结构松散并有少量脂滴。EUSA检测SOD、HO-1和NQO-1活性均呈下降趋势,ROS和caspase-3酶活性均呈升高趋势(均P<0.05)。结论雄黄体外可抑制细粒棘球蚴原头节生长,破坏原头节形态结构,降低抗氧化酶活性,该抑制作用与机体抗氧化防御系统平衡失调有关。     

论雄黄的安全性以及对其监管的建议

雄黄药用历史悠久,临床应用广泛,很多传统中药名方包括儿科方剂中含有雄黄.由于雄黄为含砷矿物药,人们常以含砷的砒霜类推其毒性,对其安全性缺乏客观认识.临床上雄黄基本以炮制品入药,而不用生品.《中国药典》2020年版记载的炮制方法为水飞法,研究证明水飞炮制的雄黄毒性较低."雄黄"被列入《医疗用毒性药品管理办法》,然而其名称...     

复方黄黛片治疗急性早幼粒细胞白血病204例经验总结

急性早幼粒细胞白血病（acute promyelocytic leukemia．APL）是一种特殊类型的急性白血病，其临床特征为极易合并感染、出血及弥漫性血管内凝血（disseminated intravascular coagulation，DIC）等并发症，死亡率较高。黄世林教授早年毕业于北京中医学院，40余年来，主要从事中医内科血液学的临床与实验研究，一直在临床一线工作，在血液学疾病的治疗上多有建树。尤其在白血病的治疗研究上造诣较深，其以攻驱毒邪理论指导组方研制成的复方黄黛片．治疗APL取得了良好的疗效。     

超细微粒径雄黄的药代动力学研究及抑瘤作用比较

目的:了解随着雄黄粒度的降低,其在血液中浓度的变化及含药血清对肿瘤细胞增殖的影响。方法:以原子荧光吸收法测定小鼠血液中的砷浓度,用MTT法测定雄黄含药血清对SMMC7721肝癌细胞的抑制作用。结果:雄黄制备成粒径不同的3种颗粒后,药代动力学参数发生了变化,随着粒径的下降,最大峰浓度上升,曲线下面积加大,生物利用度提高,含药血清对SMMC7721细胞的增殖抑制程度也加大。结论:降低雄黄粒度,可减少用药量,提高生物利用度。     

雄黄纳米微粒对人白血病细胞株HL-60的诱导分化作用

目的：探讨雄黄（As4S4）纳米微粒对于人急性早幼粒白血病细胞HL-60的抑制增殖和诱导分化作用。 方法：采用MTT法观察低浓度雄黄对HL-60细胞增殖的影响,Wright-Giemsa 染色观察细胞形态,硝基四氮唑蓝（NBT）还原反应和流式细胞术抗原检测等鉴定细胞的分化。结果：细胞经雄黄处理后呈现明显的分化形态。经0.25～1.0 μmol·L^-1 雄黄作用24 h 后,NBT阳性率升高。用0.50 μmol·L^-1雄黄处理48 h,细胞表面分化抗原CD11b表达升高,细胞周期阻滞于G1期。 结论：低浓度雄黄对HL-60细胞具有诱导分化作用。     

含与不含朱砂和雄黄的安宫牛黄丸对大鼠局灶性脑缺血的影响

目的：观察含与不含朱砂和雄黄的安宫牛黄丸对大脑中动脉栓塞模型大鼠脑梗塞面积、脑含水量及过氧化氢酶（CAT）、脂质过氧化物（LPO）、谷胱甘肽过氧化物酶（GPX）、乳酸(LD）含量的影响，探讨安宫牛黄丸中朱砂、雄黄对药效的影响。方法：动物连续灌胃给药3天后，采用大脑中动脉三氯化铁法造成大鼠脑局灶性缺血。分别用TTC染色法、烘干称重法、TBA法和按试剂盒说明书，测定大鼠脑梗塞面积、脑含水量和LPO、CAT、GPX、LD的含量。结果：含与不含朱砂、雄黄的安宫牛黄丸各剂量组大脑中动脉栓塞大鼠脑梗塞面积明显减少；脑缺血侧含水量降低；CAT和GPX含量增加，LPO和LD含量降低。结论：含与不含朱砂、雄黄的安宫牛黄丸对大脑中动脉栓塞大鼠脑组织损伤均有一定的保护作用，两者之间未见显著差异，提示安宫牛黄丸中朱砂、雄黄对大鼠脑缺血梗塞的保护作用未有明显影响。