纳米雄黄抗肿瘤的药理毒理研究及临床应用
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摘要
雄黄,辛温,有毒,归肝、大肠经,属于以毒攻毒的药物,具有解疟抗癌、解毒杀虫、燥湿祛痰的作用。古代医家常应用雄黄治疗痈肿疔疮,聚积腹痛等,近现代医家用以治疗恶性肿瘤及血液病,由古到今为临床所用。雄黄的毒性导致其用药安全范围小,现代学者将传统中药与纳米科技手段相结合,将雄黄研磨成为纳米雄黄,相比较雄黄可言,提高了生物利用度,降低了雄黄的体内毒性,将雄黄的临床应用推动到了新的高度。现代药理研究通过运用纳米雄黄干预肺癌细胞、卵巢癌细胞、皮肤癌细胞、宫颈癌细胞和白血病细胞等实验,证实纳米雄黄具有抑制细胞增殖,诱导细胞凋亡、诱导细胞分化、抑制核酸合成、抑制新生血管生成等功能,还具有抗病毒、杀菌镇痛的功效。现代毒理研究通过应用不同浓度的纳米雄黄制剂给予小鼠灌胃治疗,记录各时间段小鼠的症状体征及各项辅助检查指标,得出安全剂量下纳米雄黄对血液生化指标等影响均处于正常范围内。临床试验应用纳米雄黄外敷治疗恶性肿瘤破溃创面,发现纳米雄黄有促进患者肿瘤破溃创面愈合,减轻疼痛,缓解渗血、流脓、散发恶臭味等临床症状,提高患者生活质量的作用。并且用药简易,患者依从性好,无需住院治疗,节约医疗资源,值得临床推广应用。
Realgar is toxic and belongs to drug of poison attack,with anti-cancer,anti-pest,dry wet and expectorant effects. Ancient doctors often used realgar to treat carbuncle,boil,abdominal pain and other diseases.Modern doctors use it to treat malignant tumors and blood diseases. The toxicity of realgar results in a small range of safety in its drug use. Modern scholars combine traditional Chinese medicine with nano-technology means to grind realgar into nano-realgar. Compared with realgar,nano-realgar has an improved bioavailability and reduced toxicity in vivo. Modern pharmacological researches use nano-realgar to interven lung cancer cells,skin cancer cells,cervical cancer cells,ovarian cancer cells and leukemia cells in experiments,which confirmed that nano-realgar has effects in inhibiting cell proliferation,inducing apoptosis and cell differentiation,inhibiting nucleic acid synthesis and angiogenesis,but with antiviral,sterilization of analgesic effects. Modern toxicological studies have been conducted in mice through intragastric treatment with different concentrations of nano-realgar preparation. The symptoms and signs of mice and various auxiliary examination indexes were recorded at different time periods. It was concluded that nano-realgar has regular effects on blood biochemical indexes at safe doses. In clinical trials,nano-realgar was applied to treat damaged wound surface of malignant tumor. It was found that nano-realgar can promote healing of wound surface of tumor,alleviate pain,relieve clinical symptoms,such as bleeding,purulence and odor,and improve quality of life of patients. In addition,with a simple usage and good patient compliance,administration with nano-realgar requires no hospitalization,can save medical resources,and is worthy of clinical promotion and application.
Realgar is toxic and belongs to drug of poison attack,with anti-cancer,anti-pest,dry wet and expectorant effects. Ancient doctors often used realgar to treat carbuncle,boil,abdominal pain and other diseases.Modern doctors use it to treat malignant tumors and blood diseases. The toxicity of realgar results in a small range of safety in its drug use. Modern scholars combine traditional Chinese medicine with nano-technology means to grind realgar into nano-realgar. Compared with realgar,nano-realgar has an improved bioavailability and reduced toxicity in vivo. Modern pharmacological researches use nano-realgar to interven lung cancer cells,skin cancer cells,cervical cancer cells,ovarian cancer cells and leukemia cells in experiments,which confirmed that nano-realgar has effects in inhibiting cell proliferation,inducing apoptosis and cell differentiation,inhibiting nucleic acid synthesis and angiogenesis,but with antiviral,sterilization of analgesic effects. Modern toxicological studies have been conducted in mice through intragastric treatment with different concentrations of nano-realgar preparation. The symptoms and signs of mice and various auxiliary examination indexes were recorded at different time periods. It was concluded that nano-realgar has regular effects on blood biochemical indexes at safe doses. In clinical trials,nano-realgar was applied to treat damaged wound surface of malignant tumor. It was found that nano-realgar can promote healing of wound surface of tumor,alleviate pain,relieve clinical symptoms,such as bleeding,purulence and odor,and improve quality of life of patients. In addition,with a simple usage and good patient compliance,administration with nano-realgar requires no hospitalization,can save medical resources,and is worthy of clinical promotion and application.
引文
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[2] Pule M A,Sawoldo B,Myers G D,et al. Virus-specific T cells engineered to coexpress tumor-specific receptors:persistence and antitumor activity in individuals with neuroblastoma[J]. Nat Med,2008,14(11):1264-1270.
[3]张湉,郭伟.免疫检查点阻滞剂治疗恶性黑色素瘤进展[J].中国口腔颌面外科杂志,2017,15(4):377-381.
[4] Weizman E,Cohen C J. Engineering T-cell specificity genetically to generate anti-melanoma reactivity[J].Methods Mol Biol,2016:20.
[5] Morgan R A,Dudley M E,Wunderlich J R,et al.Cancer regression in patients after transfer of genetically engineered lymphocytes[J]. Science,2006,314(5796):126-129.
[6] Riley J L. PD-1 signaling in primary T cells[J].Immunol Rev,2009,229(1):114-125.
[7] Ghaeminia H,Perry J,Nienhuijs M E,et al. Surgical removal versus retention for the management of asymptomatic disease-free impacted wisdom teeth[J].Cochrane Database Syst Rev,2016,31(8):51-55.
[8] QIU Y Y,QIU J. Prevention and treatment of postradiotherapy dental implant complications:a review of the literature[J]. Stomatology,2016,36(7):641-644.
[9] Christina E C,Cornelia C,Edgar S. Neoadjuvant radiotherapy plus radical surgery for locally advanced stageⅢ/Ⅳoral cancer:analysis of prognostic factors affecting overall survival[J]. Oral Oncol,2016,9(60):1-7.
[10]韩建军,李传行,丁娅,等. CT导向下125Ⅰ粒子植入治疗手术后复发/转移恶性黑色素瘤的近期疗效和安全性观察[J].当代医学,2011,17(5):33-38.
[11]张素欣,陈彦平,刘哲敏,等. 125I放射性粒子植入在口腔颌面部恶性肿瘤治疗中的应用.中国肿瘤临床,2012,39(23):1943-1945.
[12]方红. UHR2000型深部微波热疗机联合化疗治疗皮肤转移癌的近期疗效分析[J].中华高血压杂志,2015,23(2):390-391.
[13]石钿印,彭歆,蔡志刚,等.术中液氮冷冻加术后放疗在治疗腮腺癌保留面神经中的应用[J].现代口腔医学杂志,2011,25(1):7-11.
[14]曾毅,何汉. 5-氟尿嘧啶联合胰岛素、庆大霉素、rh EGF换药治疗转移癌性皮肤溃疡效果观察[J].临床血液学杂志:输血与检验版,2009,22(6):671-672.
[15]程佩佩,方玉,夏叶,等.纳米雄黄炮制方法的探讨[J].中国实验方剂学杂志,2016,22(22):22-25.
[16] AN Y L,NIE F,WANG Z Y,et al. Preparation and characterization of realgar nanoparticles and their inhibitory effect on rat glioma cells[J]. Int J Nanomedicine,2011,6:3187-3194.
[17] CHENG Y X,LIU R,WANG Q,et al. Realgar-induced apoptosis of cervical cancer cell line Siha via cytochromec release and Caspase-3 and Caspase-9activation[J]. Chin J Integr Med,2012,18(5):359-365.
[18] CHEN S,FANG Y,MA L,et al. Realgar-induced apoptosis and differentiation in all-trans retinoic acid(ATRA)-sensitive NB4 and ATRA-resistant MR2 cells[J]. Int J Oncol,2012,40(4):1089-1096.
[19]王永胜,周思彤,魏虎来.纳米雄黄对药物敏感性白血病细胞的凋亡诱导作用[J].中国中药杂志,2013,38(13):2202-2205.
[20]傅承彬,王信琪,纪淑仪.雄黄治疗慢性粒细胞型白血病的近期疗效观察[J].蚌埠医学院学报,1978,3(1):11-19,10.
[21]高学熙,王信琪,马建军.雄黄治疗骨髓异常增生综合症14例[J].临床内科杂志,1998,15(3):125.
[22]高学熙,马建军,宁红程.雄黄治疗急性早幼粒细胞性白血病的疗效观察[J].临床肿瘤学杂志,1998,3(2):30-32.
[23]陆道培,王勤,刘延芳,等.中国急性早幼粒细胞白血病的治疗进展[J].北京大学学报:医学版,2002,34(5):427-430.
[24]贾彦民,刘陕西.雄黄治疗急性早幼粒细胞白血病的临床研究[J].中国基层医药,2004,11(2):138-139.
[25]关键平,袁炜,杨浩,等.雄黄治疗维甲酸耐药急性早幼粒细胞白血病临床研究[J].陕西肿瘤医学,2002,10(4):281-282.
[26]黄世林,郭爱霞,向阳,等.复方青黛片为主治疗急性早幼粒细胞白血病的临床研究[J].中华血液学杂志,1995(1):26-28,53-54.
[27]南虎松,金春姬,刘红.全反式维甲酸联合复方黄黛片序贯治疗小儿急性早幼粒细胞白血病的临床研究[J].中国现代医学杂志,2014,24(36):105-108.
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