苦参碱联合不同抗生素抗炎作用比较研究

doi:10.11843/j.issn.0366-6964.2023.10.037

摘要/Abstract

摘要： 旨在比较苦参碱与不同抗生素联合使用的抗炎作用。研究选取5种抗生素：阿莫西林、金霉素、盐酸多西环素、氟苯尼考和替米考星，以猪繁殖与呼吸综合征病毒（porcine reproductive and respiratory syndrome virus，PRRSV）5'UTR RNA和脂多糖（lipopolysaccharide，LPS）共刺激的原代猪肺泡巨噬细胞（porcine alveolar macrophage，PAMs）为炎症模型，IL-1β为检测指标，筛选与苦参碱具有相似抗炎作用的抗生素，并采用qPCR和Western blot检测苦参碱与抗生素联合用药对IL-1β的影响。结果发现，5种抗生素中，阿莫西林和金霉素对IL-1β mRNA抑制效果与苦参碱相似。联合用药结果显示，苦参碱和阿莫西林之间存在交互作用，苦参碱可替代部分阿莫西林的用量，而苦参碱和金霉素之间不存在交互作用。在抗PRRSV 5'UTR RNA和LPS共刺激诱导IL-1β表达的过程中，苦参碱和阿莫西林联合使用后，苦参碱能替代部分阿莫西林的药效，降低阿莫西林的使用量。本研究为苦参碱作为抗生素替代物的临床应用提供数据支持。

关键词: 苦参碱, 抗生素, 阿莫西林, 抗生素替代, 抗炎

Abstract: The aim of this study was to compare the anti-inflammatory effects of matrine combined with different antibiotics. Five antibiotics including amoxicillin, chlortetracycline, doxycycline hydrochloride, florfenicol and tilmicosin were selected in this experiment. Using porcine reproductive and respiratory syndrome virus (PRRSV) 5'UTR RNA and lipopolysaccharide (LPS) co-stimulated porcine alveolar macrophage (PAMs) as inflammatory model, IL-1β as the detection index, to screen antibiotics with similar anti-inflammatory effect to matrine. Then using qPCR and Western blot to detect the effect of matrine combined with antibiotics on IL-1β expression. The results showed that, the inhibitory effect of amoxicillin and aureomycin treatment group were consistent with that of matrine on IL-1β mRNA expression. When matrine was used in combination with amoxicillin or aureomycin, an interaction was noted between matrine and amoxicillin, while matrine and aureomycin lack such type of interation, which indicated that matrine could minimize part dosage of amoxicillin. These results indicated that, in the process of inhibiting IL-1β expression induced by PRRSV 5'UTR RNA and LPS co-stimulation, when combined with amoxicillin, matrine can partially replace the efficacy of amoxicillin and reduce the dosage of amoxicillin. This study provides data support for the clinical application of matrine as an antibiotic substitute.

Key words: matrine, antibiotic, amoxicillin, antibiotic substitution, anti-inflammatory

中图分类号:

S859.7

孙盼盼, 曹志刚, 凌小雅, 孙娜, 孙耀贵, 李宏全. 苦参碱联合不同抗生素抗炎作用比较研究[J]. 畜牧兽医学报, 2023, 54(10): 4411-4421.

SUN Panpan, CAO Zhigang, LING Xiaoya, SUN Na, SUN Yaogui, LI Hongquan. Comparison of Anti-inflammatory Effects of Matrine Combined with Different Antibiotics[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(10): 4411-4421.

参考文献 21

[1]	ZHU H D, CHANG X J, ZHOU J Z, et al.Co-infection analysis of bacterial and viral respiratory pathogens from clinically healthy swine in Eastern China[J].Vet Med Sci, 2021, 7(5):1815-1819.
[2]	OPRIESSNIG T, GIMÉNEZ-LIROLA L G, HALBUR P G.Polymicrobial respiratory disease in pigs[J].Anim Health Res Rev, 2011, 12(2):133-148.
[3]	VAN GUCHT S, VAN REETH K, PENSAERT M.Interaction between porcine reproductive-respiratory syndrome virus and bacterial endotoxin in the lungs of pigs:potentiation of cytokine production and respiratory disease[J].J Clin Microbiol, 2003, 41(3):960-966.
[4]	QIAO S L, FENG L L, BAO D K, et al.Porcine reproductive and respiratory syndrome virus and bacterial endotoxin act in synergy to amplify the inflammatory response of infected macrophages[J].Vet Microbiol, 2011, 149(1-2):213-220.
[5]	LI J N, WANG S N, LI C Y, et al.Secondary Haemophilus parasuis infection enhances highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) infection-mediated inflammatory responses[J].Vet Microbiol, 2017, 204:35-42.
[6]	SUN P P, SUN N, YIN W, et al.Matrine inhibits IL-1β secretion in primary porcine alveolar macrophages through the MyD88/NF-κB pathway and NLRP3 inflammasome[J].Vet Res, 2019, 50(1):53.
[7]	CECONI I, VIANO S A, MÉNDEZ D G, et al.Combined use of monensin and virginiamycin to improve rumen and liver health and performance of feedlot-finished steers[J].Transl Anim Sci, 2022, 6(4):txac154.
[8]	ESTRADA-ANGULO A, MENDOZA-CORTEZ D A, RAMOS-MÉNDEZ J L, et al.Comparing blend of essential oils plus 25-hydroxy-vit-D3 versus monensin plus virginiamycin combination in finishing feedlot cattle:growth performance, dietary energetics, and carcass traits[J].Animals (Basel), 2022, 12(13):1715.
[9]	张显东.促生长抗生素作用机理及其替代方案的重新思考[J].饲料工业, 2017, 38(11):61-64.ZHANG X D.Rethinking about mechanism of antibiotic growth promoter and its alternatives[J].Feed Industry, 2017, 38(11):61-64.(in Chinese)
[10]	印遇龙, 杨哲.天然植物替代饲用促生长抗生素的研究与展望[J].饲料工业, 2020, 41(24):1-7.YIN Y L, YANG Z.Research and prospect of natural plant substitute for antibiotic growth promoters in feed[J].Feed Industry, 2020, 41(24):1-7.(in Chinese)
[11]	李爱科, 林燕, 赵永欣.饲用抗生素替代品研究进展[J].饲料工业, 2013, 34(20):1-6.LI A K, LIN Y, ZHAO Y X.Research progress of feed antibiotic substitutes[J].Feed & Livestock, 2013, 34(20):1-6.(in Chinese)
[12]	ZHANG Q Q, YING G G, PAN C G, et al.Comprehensive evaluation of antibiotics emission and fate in the river basins of China:source analysis, multimedia modeling, and linkage to bacterial resistance[J].Environ Sci Technol, 2015, 49(11):6772-6782.
[13]	SUN N, SUN P P, LV H P, et al.Matrine displayed antiviral activity in porcine alveolar macrophages co-infected by porcine reproductive and respiratory syndrome virus and porcine circovirus type 2[J].Sci Rep, 2016, 6:24401.
[14]	SUN N, ZHANG H, SUN P P, et al.Matrine exhibits antiviral activity in a PRRSV/PCV2 co-infected mouse model[J].Phytomedicine, 2020, 77:153289.
[15]	李美娣, 武力, 陈宝妮, 等.联合应用替米考星与中药对解除免疫抑制及净化猪场蓝耳病的作用[J].养猪, 2009(3):47-48.LI M D, WU L, CHEN B N, et al.The effect of temicacin and traditional Chinese medicine on relieving immunosuppression and purifying blue ear disease in pig farms[J].Swine Production, 2009(3):47-48.(in Chinese)
[16]	XU Y L, SUN P P, WAN S X, et al.The combined usage of Matrine and Osthole inhibited endoplasmic reticulum apoptosis induced by PCV2[J].BMC Microbiol, 2020, 20(1):303.
[17]	王芳, 孙耀贵, 尹伟, 等.苦参碱联合黄芩苷对LPS诱导小鼠肺炎的影响[J].中国药理学通报, 2018, 34(8):1105-1109.WANG F, SUN Y G, YIN W, et al.Effects of matrine combined with baicalin on mouse pneumonia induced by LPS[J].Chinese Pharmacological Bulletin, 2018, 34(8):1105-1109.(in Chinese)
[18]	刘水.蛇床子素联用黄芩苷对金黄色葡萄球菌小鼠肺炎的保护作用[D].长春:吉林大学, 2016.LIU S.The Combination of osthole with baicalin protects mice from Staphylococcus aureus pneumonia[D].Changchun:Jilin University, 2016.(in Chinese)
[19]	HAN C, WANG X, ZHANG D, et al.Synergistic use of florfenicol and Salvia miltiorrhiza polysaccharide can enhance immune responses in broilers[J].Ecotoxicol Environ Saf, 2021, 210:111825.
[20]	张凤凤, 侯佳琪, 陈胡羚, 等.丹参酮乳房注入剂与头孢噻呋联合用药对奶牛乳房炎临床疗效试验[J].动物医学进展, 2021, 42(9):80-84.ZHANG F F, HOU J Q, CHEN H L, et al.Clinical trial of tanshinone intramammary infusion combined with ceftiofur on cow mastitis[J].Progress in Veterinary Medicine, 2021, 42(9):80-84.(in Chinese)
[21]	魏秀丽, 崔进, 李晴, 等.紫锥菊提取物与恩诺沙星联合用药对大肠杆菌的体外抑菌试验[J].中兽医医药杂志, 2020, 39(6):22-24.WEI X L, CUI J, LI Q, et al.Study on the combined antibacterial activeity of Echinacea extract and enrofloxacin on Escherichia coli in vitro[J].Journal of Traditional Chinese Veterinary Medicine, 2020, 39(6):22-24.(in Chinese)