中药注射剂致敏的实验模型及检测方法研究进展

doi:10.7501/j.issn.1674-6376.2023.11.026

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首页 > 过刊浏览>2023年第46卷第11期 >2023,46(11):2482-2489. DOI:10.7501/j.issn.1674-6376.2023.11.026

中药注射剂致敏的实验模型及检测方法研究进展

逯晓宇
逯晓宇
山西医科大学公共卫生学院劳动卫生学教研室, 山西太原 030001;中国辐射防护研究院放射医学与环境医学研究所, 山西太原 030006;药物毒理与放射损伤药物山西省重点实验室/中核放射毒理与放射性药物临床前评价重点实验室, 山西太原 030006
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孙鸽
孙鸽
中国辐射防护研究院放射医学与环境医学研究所, 山西太原 030006;药物毒理与放射损伤药物山西省重点实验室/中核放射毒理与放射性药物临床前评价重点实验室, 山西太原 030006
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郭婷婷
郭婷婷
中国辐射防护研究院放射医学与环境医学研究所, 山西太原 030006;药物毒理与放射损伤药物山西省重点实验室/中核放射毒理与放射性药物临床前评价重点实验室, 山西太原 030006
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秦秀军
秦秀军
中国辐射防护研究院放射医学与环境医学研究所, 山西太原 030006;药物毒理与放射损伤药物山西省重点实验室/中核放射毒理与放射性药物临床前评价重点实验室, 山西太原 030006
通讯作者.
Email: xiujunqin@163.com
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Research progress on experimental models and detection methods of sensitization by traditional Chinese medicine injections

LU Xiaoyu
LU Xiaoyu
Department of Labor Health, School of Public Health, Shanxi Medical University, Taiyuan 030001, China;Department of Radiology and Environment Medicine, China Institute for Radiation Protection, Taiyuan 030006, China;Key Laboratory of Drug Toxicology and Radiation Damage Drugs of Shanxi Province/Key Laboratory of Mesonuclear Radiation Toxicology and Preclinical Evaluation of Radiopharmaceuticals, Taiyuan 030006, China
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SUN Ge
SUN Ge
Department of Radiology and Environment Medicine, China Institute for Radiation Protection, Taiyuan 030006, China;Key Laboratory of Drug Toxicology and Radiation Damage Drugs of Shanxi Province/Key Laboratory of Mesonuclear Radiation Toxicology and Preclinical Evaluation of Radiopharmaceuticals, Taiyuan 030006, China
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GUO Tingting
GUO Tingting
Department of Radiology and Environment Medicine, China Institute for Radiation Protection, Taiyuan 030006, China;Key Laboratory of Drug Toxicology and Radiation Damage Drugs of Shanxi Province/Key Laboratory of Mesonuclear Radiation Toxicology and Preclinical Evaluation of Radiopharmaceuticals, Taiyuan 030006, China
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QIN Xiujun
QIN Xiujun
Department of Radiology and Environment Medicine, China Institute for Radiation Protection, Taiyuan 030006, China;Key Laboratory of Drug Toxicology and Radiation Damage Drugs of Shanxi Province/Key Laboratory of Mesonuclear Radiation Toxicology and Preclinical Evaluation of Radiopharmaceuticals, Taiyuan 030006, China
Contact Author.
Email: xiujunqin@163.com
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发布日期：2023-11-09

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[关键词]

中药注射剂 ; Ⅰ型过敏反应 ; 类过敏反应 ; 细胞模型 ; 动物模型

[摘要]

随着中药注射剂在临床上应用的日益广泛，其不良反应成为中药安全评价研究的热点和难点之一，日渐引起重视。中药注射剂常导致Ⅰ型过敏反应及类过敏反应，近年来针对这2种过敏反应已经开发出多种细胞、类过敏反应动物模型、Ⅰ型过敏反应动物模型以及酶联免疫吸附（ELISA）法、高通量筛选分离方法、虚拟技术筛选等。通过综述近年来中药注射剂致敏实验模型及检测方法原理、适用性及局限性，以期为建立新型过敏原筛选方法、寻找中药注射剂过敏原和研究潜在致敏机制提供更多参考。

[Key word]

traditional Chinese medicine injections ; type Ⅰ allergic reaction ; anaphylactoid reactions ; cell model ; animal model

[Abstract]

With the increasing application of traditional Chinese medicine (TCM) injection in clinic, the adverse reactions have become one of the hot spots and difficulties in the study of TCM safety evaluation, and has increasingly attracted people's attention. TCM injections often cause type I allergic reaction and anaphylactoid reactions. In recent years, a variety of cells, animal models of anaphylactoid reaction, animal models of type Ⅰ anaphylactoid reaction, and ELISA, a variety of high-throughput screening and isolation methods, and virtual technology screening have been developed for these two kinds of allergic reactions.In this paper, the principles, applicability and limitations of experimental models and detection methods for sensitization of traditional Chinese medicine injections in recent years are reviewed, in order to provide more references for establishing new screening methods for allergens, finding allergens for TCM injections, and studying potential sensitization mechanisms.

[中图分类号]

R285.5；R943

[基金项目]

山西省科技合作交流专项项目（202104041101032）；中国辐射防护研究院自主科研项目（YP21010202）

引用本文 / Get Citation

逯晓宇,孙鸽,郭婷婷,秦秀军.中药注射剂致敏的实验模型及检测方法研究进展[J].药物评价研究,2023,46(11):2482-2489

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历史 / History

收稿日期: 2023-05-03

在线发布日期: 2023-11-09

出版日期: 2023-11-08

[1] Tan L, Li M, Lin Y. Safety concerns of traditional Chinese medicine injections used in Chinese children[J]. Evid Based Compl Alternat Med, 2019, doi:10.1155/2019/8310368.

[2] Yang M, Zhu S J, Shen C, et al. Clinical application of Chinese herbal injection for cancer care:Evidencemapping of the systematic reviews, Meta-analyses, and randomized controlled trials[J]. Front Pharmacol, 2021, doi:10.3389/fphar.2021.666368.

[3] Zeng M, Liao Q, Cui Y, et al. The therapeutic efficacy and safety of traditional Chinese medicine injection combined with low-molecular-weight heparin on the acute lower extremity deep venous thrombosis:A protocol for systematic review and network Metaanalysis[J]. Medicine (Baltimore), 2021, 100(50):e28039.

[4] Zhang Y, Lu P, Qin H, et al. Traditional Chinese medicine combined with pulmonary drug delivery system and idiopathic pulmonary fibrosis:Rationale and therapeutic potential[J]. Biomed Pharmacother, 2021, 133:111072.

[5] Huang R, Cai Y, Yang L, et al. Safety of traditional Chinese medicine injection based on spontaneous reporting system from 2014 to 2019 in Hubei Province, China[J]. Sci Rep, 2021, 11(1):8875.

[6] 游鹏程, 王颂. 138例红花黄色素注射液临床使用分析[J]. 中国药物警戒, 2014, 11(2):112-113. You P C, Wang S. Clinical analysis of 138 cases of Carthamus Yellow for Injection[J]. Chin J Pharmacovig, 2014, 11(2):112-113.

[7] 徐晨阳, 陈云建. 中药注射剂的不良反应及其成因和防治措施[J]. 中国民族民间医药, 2018, 27(24):144-147. Xu C Y, Chen Y J. The adverse rreaction of ttraditional Chinese medicine injection, its cause and preventive measures[J]. Chin J Ethnomed Ethnopharm, 2018, 27(24):144-147.

[8] 李汉成, 朱钊铭, 曾茗, 等. 中药注射剂类过敏动物模型研究进展[J]. 今日药学, 2023, 33(3):175-179. Li H C, Zhu Z M, Zeng M, et al. Advances in animal models of anaphylactoid reaction to traditional Chinese medicine injection[J]. Pharm Today, 2023, 33(3):175-179.

[9] 张帆, 王璐, 戚进, 等. 中药注射剂致类过敏反应评价模型研究进展[J]. 海峡药学, 2019, 31(9):10-13. Zhang F, Wang L, Qi J, et al. Research progress of the evaluation model of pseudoallergic reactions induced by traditional Chinese medicine injection[J]. Strait Pharm J, 2019, 31(9):10-13.

[10] 万梅绪, 宋美珍, 李智, 等. 小鼠耳廓蓝染类过敏检测方法用于注射益气复脉(冻干)的质控研究[J]. 药物评价研究, 2018, 41(3):405-410, 428. Wang M X, Song M Z, Li Z, et al. Quality control study on Yiqi Fumai Lyophilized Injection for mouse ear blue staining pseudo-allergic reactions[J]. Drug Eval Res, 2018, 41(3):405-410, 428.

[11] 李璎峪, 文雯, 刘红宇, 等. 双黄连注射剂及参麦注射液类过敏反应的剂量相关性研究[J]. 湖南中医药大学学报, 2022, 42(11):1843-1848. Li Y Y, Wen W, Liu H Y, et al. Dose correlation study of anaphylactoid reaction induced by Shuanghuanglian Injection and Shenmai Injection[J]. J Hunan Univ Chin Med, 2022, 42(11):1843-1848.

[12] 崔宏玉, 易艳, 李春英, 等. 清开灵注射液类过敏反应的实验研究[J]. 中国中药杂志, 2014, 39(3):511-514. Cui H Y, Yi Y, Li C Y, et al. Experimental study on pseudoallergic reaction of Qingkailing injection[J]. China J Chin Mater Med, 2014, 39(3):511-514.

[13] 康黎静, 谢家骏, 赵琳, 等. 大鼠皮肤类过敏试验评定标准的探讨[J]. 中国中药杂志, 2015, 40(20):4044-4051. Kang L J, Xie J J, Zhao L, et al. Evaluation criteria for rat skin anaphylactoid test[J]. China J Chin Mater Med, 2015, 40(20):4044-4051.

[14] 易艳, 李春英, 赵雍, 等. 清开灵注射液类过敏反应特点及致敏物质初步筛选研究[J]. 中国中药杂志, 2018, 43(1):154-159. Yi Y, Li C Y, Zhao Y, et al. Pseudoallergic reaction characteristics of Qingkailing Injection and preliminary screening of allergic substances[J]. China J Chin Mater Med, 2018, 43(1):154-159.

[15] 张宇实, 易艳, 李春英, 等. 中药注射剂类过敏反应临床前评价:动物品系和性别差异研究[J]. 中国中药杂志, 2015, 40(14):2717-2722. Zhang Y S, Yi Y, Li C Y, et al. Preclinical evaluation of pseudoallergic reactions on Chinese herbal injections:study on animal strain and gender difference[J]. China J Chin Mater Med, 2015, 40(14):2717-2722.

[16] 陈文培, 张子扬, 周成浩, 等. 大鼠被动皮肤过敏反应实验条件的优化[J]. 中国药理学与毒理学杂志, 2016, 30(7):747-753. Chen W P, Zhang Z Y, Zhou C H, et al. Optimization of parameters of passive cutaneous anaphylaxis in rats[J]. Chin J Pharmacol Toxicol, 2016, 30(7):747-753.

[17] 陈怀广, 杨灿邦, 陈晓蕊, 等. 细辛脑注射液被动皮肤过敏试验及对血清IgE的影响[J]. 广东药科大学学报, 2020, 36(1):67-70. Chen H G, Yang C B, Chen X R, et al. A study on the passive cutaneous anaphylaxis test of asarone injection and its influence on serum IgE[J]. J Guangdong Pharm Univ, 2020, 36(1):67-70.

[18] 井中旭, 张妍妍, 冯宇飞. 改良被动皮肤过敏试验方法的建立[J]. 黑龙江中医药, 2017, 46(1):78-80. Jin Z X, Zhang Y Y, Feng Y F. Establishment of an improved test method for passive skin allergy[J]. Heilongjiang J Tradit Chin Med, 2017, 46(1):78-80.

[19] 毛宏梅, 韩超, 崔璐, 等. 4种不同类型药物的豚鼠全身主动过敏试验研究[J]. 军事医学, 2016, 40(5):405-408. Mao H M, Han C, Cui L, et al. Active systemic anaphylaxis test of guinea pigs for four different types of drugs[J]. Milit Med Sci, 2016, 40(5):405-408.

[20] 易艳, 李春英, 赵雍, 等. 一种新的小鼠过敏试验模型的建立及其在中药注射剂致敏性评价中的应用[J]. 中国中药杂志, 2022, 47(13):3581-3588. Yi Y, Li C Y, Zhao Y, et al. A novel mouse allergy tested model and its application for traditional Chinese medicine injections's allergy evaluation[J]. China J Chin Mater Med, 2022, 47(13):3581-3588.

[21] 刘兆华, 刘兆平, 周庚寅. 腘窝淋巴结试验在药物超敏反应研究中的应用[J]. 中国药理学与毒理学杂志, 2009, 23(1):70-75. Liu Z H, Liu Z P, Zhou G Y. Application of popliteal lymph node assay in the study of drug hypersensitivity[J]. Chin J Pharmacol Toxicol, 2009, 23(1):70-75.

[22] Nierkens S, Nieuwenhuijsen L, Thomas M, et al. Evaluation of the use of reporter antigens in an auricular lymph node assay to assess the immunosensitizing potential of drugs[J]. Toxicol Sci, 2004, 79(1):90-97.

[23] 林琳, 范潇予, 李恩灿, 等. 小鼠腘窝淋巴结模型评价3 种中药注射液的潜在免疫毒性[J]. 癌变·畸变·突变, 2018, 30(4):275-278, 285. Lin L,Fan X Y,Li E C, et al. Potential immunotoxicity of three traditional Chinese medicines using the popliteal lymph node assay in mice[J]. Carcinog Teratog Mutag, 2018, 30(4):275-278, 285.

[24] Ravel G, Descotes J. Popliteal lymph node assay:facts and perspectives[J]. J Appl Toxicol, 2005, 25(6):451-458

[25] 申茜, 李珍, 王玉, 等. 绿原酸致RBL-2H3细胞脱颗粒反应及机制研究[J]. 药物评价研究, 2023, 46(2):305-310. Shen Q, Li Z, Wang Y, et al. Degranulation response and mechanism of chlorogenic acid on RBL-2H3 cells[J]. Drug Eval Res, 2023, 46(2):305-310.

[26] 廖国平. 清开灵注射液致小鼠IgE介导的过敏反应模型建立与绿原酸变应原性研究[D]. 广州:南方医科大学, 2012. Liao G P. The study on modeling a murine model of immunoglobulin-E (IgE) -mediated Qingkailing injection anaphylaxis and the allergenicity of chlorogenic acid[D]. Guangzhou:Southern Medical University, 2012.

[27] 李黎明, 金若敏, 谢家骏, 等. 致敏RBL-2H3细胞在清开灵、痰热清中药注射剂过敏性评价中的应用[J]. 中草药, 2015, 46(1):86-89. Li L M, Jin R M, Xie J J, et al. Application of RBL-2H3 cells on allergenicity assessment of Qingkailing and Tanreqing Injections[J]. Chin Tradit Herbal Drugs, 2015, 46(1):86-89.

[28] Chan C L. Effects of Taiwan medicinal plants on asthmatic mediators releasing in mouse mastocytoma cell line P815[D]. Tainan:National Cheng Kung University, 2008.

[29] 刘玲, 王红, 朱星宇, 等. 血必净注射液及其成分对肥大细胞脱颗粒作用的影响[J]. 药学与临床研究, 2022, 30(3):207-211. Liu L, Wang H, Zhu X Y, et al. Effects of Xuebijing Injections and their components on degranulation of mast cells[J]. Pharm Clin Res, 2022, 30(3):207-211.

[30] Peng B, He R, Xu Q, et al. Comparison of RBL-2H3 and P815 cell lines for establishing in vitro model of mast cell degranulation[J]. Chin J Nat Med, 2011, 9(3):227-231.

[31] 朱远洪, 王青, 董燕, 等. 生脉注射剂致RBL-2H3细胞与大鼠腹腔肥大细胞脱颗粒研究[J]. 广州中医药大学学报, 2014, 31(3):410-413, 417, 496. Zhang Y H, Wang Q, Dong Y, et al. Effect of Shengmai Injection on degranulation of RBL-2H3 cells and rat peritoneal mast cells[J]. J Guangzhou Univ Tradit Chin Med, 2014, 31(3):410-413, 417, 496.

[32] 李咏梅, 刘炯, 赵源, 等. 大鼠腹腔肥大细胞与RBL-2H3细胞脱颗粒方法的建立及其在中药注射剂安全性评价上的应用[J]. 中国实验方剂学杂志, 2011, 17(22):152-157. Li Y M, Liu J, Zhao Y, et al. Studies on degranuation of rat peritoneal mast cells and RBL-2H3 cells caused by traditional Chinese medicine injections[J]. Chin J Exp Tradit Med Form, 2011, 17(22):152-157.

[33] Nguyen S, Rupprecht C P, Haque A, et al. Mechanisms governing anaphylaxis:Inflammatory cells, mediators, endothelial gap junctions and beyond[J]. Int J Mol Sci, 2021, 22(15):7785.

[34] Han J, Zhao Y, Zhang Y, et al. RhoA/ROCK signaling pathway mediates Shuanghuanglian Injection-induced pseudo-allergic reactions[J]. Front Pharmacol, 2018, 9:87.

[35] Han J, Yi Y, Li C, et al. Involvement of histamine and RhoA/ROCK in penicillin immediate hypersensitivity reactions[J]. Sci Rep, 2016, 6:33192.

[36] 尚再卓, 于瑞明, 张莉萍, 等. 猪δ冠状病毒抗体间接ELISA检测方法的建立[J]. 中国兽医学报, 2022, 42(12):2339-2346. Shang Z Z, Yu R M, Zhang L P, et al. Establishment of indirect ELISA for detection of porcine deltacoronavirus antibody[J]. Chin J Veterin Sci, 2022, 42(12):2339-2346.

[37] 刘丽鹤, 尹利辉, 金少鸿. 中药注射剂过敏反应体外评价方法研究进展[J]. 药物分析杂志, 2013, 33(8):1439- 1446. Liu L H, Yin L H, Jin S H. Review on in vitro experimental methods for evaluating hypersensitivity of traditional Chinese medicine injections[J]. Chin J Pharm Anal, 2013, 33(8):1439-1446.

[38] 刘润南, 包小燕, 曾姣丽, 等. 免疫指纹图谱法研究双黄连注射剂中绿原酸的致敏性[J]. 中南药学, 2019, 17(3):352-355. Liu R N, Bao X Y, Zeng J L, et al. Sensitivity of chlorogenic acid in Shuanghuanglian Injection by immune fingerprinting[J]. Central South Pharm, 2019, 17(3):352-355.

[39] 曾姣丽, 贺福元, 唐昱, 等. 双黄连注射剂中黄芩苷致敏原性的研究[J]. 中国实验方剂学杂志, 2012, 18(1):102-106. Zeng J L, He F Y, Tang Y, et al. Study of Allergenicity of Baicalin in Shuanghuanglian Injection[J]. Chin J Exp Tradit Med Form, 2012, 18(1):102-106.

[40] 尹婕, 尹利辉, 胡昌勤, 等. 双黄连注射液中半抗原成分酶联免疫检测方法的建立[J]. 中成药, 2013, 35(12):2678-2683. Yin J, Yin L H, Hu C Q, et al. Enzyme-linked immunosorbent assay of hapten in Shuanghuanglian Injection[J]. Chin Tradit Pat Med, 2013, 35(12):2678- 2683.

[41] 文雯, 贺福元, 刘文龙, 等. 基于免疫指纹图谱法筛查双黄连注射剂的致敏成分[J]. 中国中药杂志, 2019, 44(8):1588-1595. Wen W, He F Y, Liu W L, et al. Screening of Shuanghuanglian Injection allergenic ingredients based on immune fingerprint[J]. China J Chin Mater Med, 2019, 44(8):1588-1595.

[42] 贺福元, 邓凯文, 曾姣丽, 等. 中药注射剂致敏成分群筛查方法研究的现状与免疫综合法[J]. 中国中药杂志, 2012, 37(19):2836-2841. He F Y, Deng K W, Zeng J L, et al. Current state of studies on screening method for sensitinogens in injections for traditional Chinese medicine and synthetic immunity method[J]. China J Chin Mater Med, 2012, 37(19):2836-2841.

[43] Han S, Lv Y, Xue W, et al. Screening anaphylactic components of Mailuoning Injection by using rat basophilic leukemia-2H3 cell membrane chromatography coupled with HPLC-ESI-TOF-MS[J]. J Sep Sci, 2016, 39(3):466-472.

[44] Bu Y, Hu Q, Xu K, et al. Improved cell membrane bioaffinity sample pretreatment technique with enhanced stability for screening of potential allergenic components from traditional Chinese medicine injections[J]. J Mater Chem B, 2018, 6(4):624-633.

[45] Wang F, Li C Y, Zheng Y F, et al. Identification of the allergenic ingredients in Reduning Injection by ultrafiltration and high-performance liquid chromatography[J]. J Immunol Res, 2016, 2016:4895672.

[46] 冯迪, 刘湲, 孙影, 等. 基于计算机虚拟筛选技术寻找NDM-1抑制剂[J]. 国外医药:抗生素分册, 2018, 39(2):111-115. Feng D, Liu Y, Sun Y, Zheng H, et al. Search for NDM-1 inhibitors based on computer virtual screening techniques[J]. World Notes Antibiot, 2018, 39(2):111-115.

[47] 庞菲, 王弯弯, 郝瑞瑞, 等. 香丹注射液中致类过敏反应成分筛选及机制初探[J]. 中草药, 2022, 53(20):6500-6508. Pang F, Wang W W, Hao R R, et al. Screening and preliminary mechanism of inducer of anaphylactic reaction in Xiangdan Injection[J]. Chin Tradit Herbal Drugs, 2022, 53(20):6500-6508.

[48] Rebala G, Ravi A, Churiwala S. An Introduction to Machine Learning[M]. Cham:Springer Nature Switzerland AG, 2019:1-3.

[49] 刘景陶. 基于药效团模型的药物设计与筛选[J]. 科技创新与应用, 2020(34):69-71. Liu J T. Drug design and screening based on pharmacophore model[J]. Technol Innov Appl, 2020(34):69-71.

[50] 张佳颖. 以含三七皂苷成分中药注射液为例建立ADR前置预测系统[D]. 成都:电子科技大学, 2020. Zhang J Y. Establishment of ADR prediction system for traditional Chinese medicine injection containing panax notoginseng saponins[D]. Chengdu:University of Electronic Science and Technology of China, 2020.

[51] 高宇, 王凤雪, 刘海波. 虚拟筛选技术在天然产物新药研发中的应用[J]. 国际药学研究杂志, 2020, 47(8):602-608. Gao Y, Wang F X, Liu H B. Application of in silico screening technology in the medical research of natural products[J]. J Int Pharm Res, 2020, 47(8):602-608.

[52] 章新友, 张亚明, 刘梦玲, 等. 虚拟筛选技术在中药研究中的应用[J]. 中国新药杂志, 2022, 31(17):1676-1683. Zhang X Y, Zhang Y M, Liu M L, et al. Application of virtual screening technology in the research of traditional Chinese medicine[J]. Chin J New Drugs, 2022, 31(17):1676-1683.

[53] Han J, Zhang Y, Pan C, et al. Forsythoside A and forsythoside B contribute to Shuanghuanglian Injectioninduced pseudoallergic reactions through the RhoA/ROCK signaling pathway[J]. Int J Mol Sci, 2019, 20(24):6266.