连翘苷元大鼠28天重复静脉注射给药毒性研究

doi:10.19803/j.1672-8629.20250017

摘要/Abstract

摘要： 目的观察SD大鼠连续28 d重复静脉注射给药连翘苷元,考察动物可能出现的毒性反应及可逆性,为连翘苷元的临床使用提供参考。方法选用SPF级别SD大鼠150只,按体重随机分为5组,溶媒对照组,氢化可的松阳性对照组（30 mg·kg^-1·d^-1）,连翘苷元低、中、高剂量组（分别为4、12、40 mg·kg^-1·d^-1）。每组30只,雌雄各半。每日给药2次,上、下午各1次,连续给药28 d,停药恢复观察28 d。实验期间观察动物的一般状况,对体重、摄食量、血液学、血生化、眼科检查、尿液分析、脏器重量及系数和组织病理学进行检查。结果连续给药28 d,氢化可的松注射液对照组,动物体重、血生化、血液学、尿液检测均出现异常结果;胸腺发生萎缩,皮质区淋巴细胞吞噬作用增加,出现满天星样巨噬细胞。恢复期结束氢化可的松注射液对照组,动物体重、血生化、血液学、尿液检测均未出现异常结果;胸腺恢复正常,表明该病变为可逆性损伤。连翘苷元低、中、高剂量组连续静脉注射给药28 d及停药28 d,动物的一般状态正常,体重、摄食量、尿常规、血液学、凝血指标、血清生化学、血清电解质等指标及病理组织学检查未观察到可能与连翘苷元相关的异常改变。结论本研究条件下,未发现与连翘苷元毒性相关的异常改变,连翘苷元静脉注射给药28 d对SD大鼠无明显毒性。

关键词: 连翘苷元, 重复给药, 毒性, 免疫毒性, 静脉注射, 大鼠

Abstract: Objective To observe the possible toxic reactions and reversibility in SD rats after 28 consecutive days of repeated intravenous injection of forsythoside aglycone, and to provide a reference for its clinical applications. Methods One hundred and fifty SPF-grade rats (half male and half female) were randomly divided into 5 groups according to body weight: the solvent control group, hydrocortisone positive control group (30 mg·kg^-1·d^-1), and low, medium and high dose forsythoside aglycone groups (4、12、40 mg·kg^-1·d^-1), with 30 rats in each group. The rats were given respective drugs twice a day, in the morning and afternoon and for 28 consecutive days, followed by a 28-day recovery period. During the experiment, the condition of the rats was observed, and the body weight, food intake, hematology, blood biochemistry, ophthalmology, results of urine analysis, organ weight and coefficient, and data on histopathological examination were recorded. Results After 28 days of continuous administration, the hydrocortisone positive control group was abnormal in body weight, blood biochemistry, hematology and urine tests. Histopathological examination revealed atrophy of the thymus and increased phagocytosis of lymphocytes in the cortex, with starry-sky macrophages. At the end of recovery, no abnormal results were observed in body weight, blood biochemistry, hematology or urine tests in the hydrocortisone positive control group. Histopathological examination showed that the thymus returned to normal, suggesting that the lesion was reversible. After 28 days of continuous intravenous injection of forsythoside aglycone and 28-day recovery, the rats were in stable condition, and no abnormal changes related to forsythoside aglycone were observed in body weight, food intake, urine routine indexes, hematology, coagulation indicators, serum biochemistry, serum electrolytes or results of histopathological examination. Conclusion Under the conditions of this experiment, no abnormalities related to the toxicity of forsythoside aglycone are found. Twenty-eight days of intravenous injection of forsythoside aglycone have no obvious toxicity on SD rats.

Key words: Forsythoside Aglycone, Repeated Administration, Toxicity, Immunotoxicity, Injection, Rats

中图分类号:

R978
R994.11

仇德洋, 谭玉军, 王达丽, 李国超, 姚方方, 赵云, 杜建才, 李斌, 姚景春. 连翘苷元大鼠28天重复静脉注射给药毒性研究[J]. 中国药物警戒, 2025, 22(9): 994-1002.

QIU Deyang, TAN Yujun, WANG Dali, LI Guochao, YAO Fangfang, ZHAO Yun, DU Jiancai, LI Bin, YAO Jingchun. Toxicity Caused by 28 Days of Repeated Intravenous Injection of Forsythoside Aglycone in Rats[J]. Chinese Journal of Pharmacovigilance, 2025, 22(9): 994-1002.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://zgywjj.magtechjournal.com/CN/10.19803/j.1672-8629.20250017

https://zgywjj.magtechjournal.com/CN/Y2025/V22/I9/994

参考文献

[1] SHEN YQ, XIAO D, JIN J.Study on Clinical Efficacy of Shuganning Combined with Magnesium Isoglycyrrhizinate in the Treatment of Acute Hepatitis[J]. China Practical Medicine(中国实用医药), 2025, 20(1): 6-10.
[2] JIANG YH, CHENG G, FU CJ, et al.Material Basis and Action Mechanism of Ganlexin Capsules in the Treatment of Acute Hepatitis[J]. Guizhou Science(贵州科学), 2024, 42(3): 46-51.
[3] ZHAO ZY.Study on the Effect and Mechanism of Ethanol Extract from Purple Rice Bran on Improving Acute Hepatitis in Mice[D]. Kunming: Kunming University of Science and Technology, 2024.
[4] CHEN YX, CHEN C, LU LH, et al.Triptolide in the Treatment of Osteoarthritis: Network Pharmacology Analysis and Animal Model Validation[J]. Chinese Journal of Tissue Engineering Research(中国组织工程研究), 2026, 30(4): 805-815.
[5] WU HT, LIN JH.Disease Burden and Harm of Osteoarthritis[J]. Medical Journal of Peking Union Medical College Hospital(协和医学杂志), 2025, 16(1): 5-12.
[6] LI L, DU LL, TONG XH, et al.Research Progress on the Treatment of Mastitis with Forsythia suspensa[J]. Shanxi Journal of Traditional Chinese Medicine(山西中医), 2025, 41(6): 65-67.
[7] ZHOU YN, WANG RM, WANG D, et al.Research Progress on Anti-inflammatory Effects of Natural Active Components of Forsythia suspensa[J]. Modern Journal of Integrated Traditional Chinese and Western Medicine(现代中西医结合杂志), 2025, 34(12): 1725-1728.
[8] YUAN A, ZHAO MJ, LI Y, et al.The Review of Pharmacological Effects of Lianqiao[J]. Pharmacy and Clinics of Chinese Materia Medica(中药与临床), 2015, 6(5): 56-59.
[9] WANG EL, YAO JC, LIU Z.Effect of Forsythiaside on Immunological Hepatic Fibrosis of Rats[J]. Drug Evaluation Research(药物评价研究), 2015, 38(2): 161-164.
[10] Professional Committee of Reproductive Toxicology of Chinese Society of Toxicology. Association of Chinese Experimental Primates Breeding and Development. Proceedings of the Academic Exchange Conference on the Theory and Technology of Reproductive Toxicology and Pharmacology and the R&D of Scientific and Technological Products in 2019 and the Second Session of the Fifth General Assembly of the Association of Chinese Experimental Primates Breeding and Development in 2019 (2019年生殖毒理药理学理论与技术及科技产品研发学术交流大会暨2019年中国实验灵长类养殖开发协会第五届二次全体会员大会论文集)[C]. Linyi: Academic Exchange Conference on the Theory and Technology of Reproductive Toxicology and Pharmacology and the R&D of Scientific and Technological Products in 2019 and the Second Session of the Fifth General Assembly of the Association of Chinese Experimental Primates Breeding and Development, 2019.
[11] YANG JL, LI C, LIU Q, et al.Effects of Forsythoside on Oxidative Stress and Renal Function in Aged Rats[J]. Chinese Journal of Clinical Anatomy(中国临床解剖学杂志), 2019, 37(1): 77-82.
[12] GUO HY, QI LH, WANG L.Effects of Phillyrin on Chronic Pelvic Inflammatory Disease Rats by Regulating CXCL12/CXCR4 Signaling Pathway[J]. Shaanxi Medical Journal(陕西医学杂志), 2025, 54(2): 175-180.
[13] ZHANG YS, ZHANG Y, ZHANG X, et al.Effect of Phillyrin on Neuronal Apoptosis in Neonatal Rats with Hypoxic-Ischemic Encephalopathy Based on Nrf2/NF-κB Signaling Pathway[J]. Chinese Traditional and Herbal Drugs(中草药), 2025, 56(10): 3577-3584.
[14] ZHANG GM, WANG EL, LI GY, et al. Application of Forsythia Aglycone in Preparation of Drugs for Prevention or Treatment of Liver Fibrosis (连翘苷元在制备预防或治疗肝纤维化药物中的应用): China, 201510005489.6[P].2018-07-06.
[15] ZHAO ZQ, SONG HY, ZHANG YX, et al. The Use of Forsythia Aglycone in the Preparation of Drugs for Rheumatoid Arthritis (连翘苷元在制备治疗类风湿关节炎药物中的用途): China, 201410504690.4[P].2016-04-20.
[16] SUN L, SUN N, XU P, et al.Research Progress on Chemical Constituents of Lianqiao (Forsythiae Fructus) and Its Mechanisms of Action against Respiratory Viruses[J]. Guiding Journal of Traditional Chinese Medicine and Pharmacy(中医药导报), 2025, 31(3): 146-154.
[17] FU YJ, YUAN LJ, CHEN J, et al.The Effects and Mechanisms of Forsythla Suspense on the Expression of Foxp'on Splenocytes and Level of Treg in Peripheralblood in Severely Burnt Rats[J]. Journal of Cellular and Molecular Immunology(细胞与分子免疫学杂志), 2009, 25(10): 935-937.
[18] LIU Y, ZHU T, LI QL, et al.Effect of Phillyrin on Cardiomyocyte Injury Induced by High Glucose through Regulating cAMP/PKA Signaling Pathway[J]. Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease(中西医结合心脑血管病杂志), 2025, 23(1): 55-60.
[19] LU S, CHEN SN, GUAN JY, et al.Effects of Forsythoside on Cell Functions of RAW 264.7 Stimulated by LPS[J]. Chinese Agricultural Science Bulletin(中国农学通报), 2012, 28(20): 58-62.
[20] SHEN H, LU S, CHEN SN, et al.Effects of Forsythoside on Proliferation and Secretion of Mouse Spleen Lymphocytes in vitro[J]. Acta laboratorium Animalis Scientia Sinica(中国实验动物学报), 2012, 20(4): 66-70.
[21] YU HY, ZHANG XY, YE Y, et al.Progress in Research on Pharmacological Mechanism of Forsythoside A Based on Signaling Pathways[J]. Lishizhen Medicine and Materia Medica Research(时珍国医国药), 2025, 36(1): 137-143.
[22] JIANG CZ, LIU CH, PAN YL, et al.Immunomodulatory Effects of Two Plant Ferments on Hydrocortisone-Induced Immunosuppression in Mice[J]. Chinese Journal of Food Science(中国食品学报), 2018, 18(8): 42-47.
[23] WANG Y.Protective Effect of Artesunate on Hydrocortisone-Induced Immunosuppression in Mice and Its Mechanism[D]. Zunyi: Zunyi Medical University, 2020.
[24] WU XL, GUO YZ, FAN L, et al.Immunoprotective Effect of Tangcaopian on Mice Injected with Hydrocortisone[J]. Chinese Journal of Hospital Pharmacy(中国医院药学杂志), 2013, 33(23): 1931-1934.