文献类型：期刊文献

中文题名：盐酸坦索罗辛与宁米泰胶囊联合用药调控β-内酰胺酶相关基因及溶血和毒力基因表达

英文题名：Potent Anti-bacteria Activity of Tamsulosin Hydrochloride and Ningmitai Capsule in Combination by Regulating the Gene Expression Related toβ-Lactamase,Hemolysis,and Virulence

作者：程莎 孙宝飞 余佳 黄丽荣 骆衡

第一作者：程莎

机构：[1]贵州医科大学药用植物功效与利用国家重点实验室,贵阳550014;[2]贵州省中国科学院天然产物化学重点实验室,贵阳550014;[3]贵州理工学院食品药品制造工程学院制药工程教研室,贵阳550003;[4]贵州医科大学基础医学院解剖学教研室,贵阳550014

第一机构：贵州医科大学药用植物功效与利用国家重点实验室,贵阳550014

年份：2022

卷号：38

期号：8

起止页码：1043-1052

中文期刊名：中国生物化学与分子生物学报

外文期刊名：Chinese Journal of Biochemistry and Molecular Biology

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD_E2021_2022】；PubMed;

基金：贵州省科技支持计划(No.QKHZC[2020]4Y161,QKHZC[2021]一般412,和QKHZC[2021]一般450)资助。

语种：中文

中文关键词：盐酸坦索罗辛;宁泌泰胶囊;联合用药;基因表达

外文关键词：Tamsulosin hydrochloride;Ningmitai;drug combination;gene expression

摘要：盐酸坦索罗辛(TSH)是一种选择性α_(1)肾上腺素受体阻滞剂,主要用于治疗良性前列腺增生症。宁泌泰胶囊(NMT)是根据中医理论建立的配方制剂,具有清热解毒、利尿排尿等功效,主要用于湿热蕴结淋淋、淋湿酸痛、尿血、下尿路感染与慢性前列腺炎。研究显示,TSH可与多种药物联合用于治疗微生物感染和抗生素耐药,显示出较好的治疗效果和应用前景;NMT对大肠杆菌、变形杆菌、淋病奈瑟菌、粪链球菌、金黄色葡萄球菌等多种致病菌也具有明显的抑菌和杀菌作用。提示这2种药物联合应用可能对临床细菌具有显著的抗菌活性。本研究采用比浊法,在肺炎克雷伯菌(K.pneumonia)、金黄色葡萄球菌(S.aureus)和枯草芽孢杆菌(B.subtilis)中,体外检测TSH与NMT联合应用的抗菌活性。研究发现,TSH与NMT联合应用表现出显著的抗菌活性,对3种菌株的体外抑制活性均强于单一治疗。建立感染动物模型,在体内检测TSH与NMT联合应用的抗菌活性。结果表明,2种药物联合使用对肺炎克雷伯菌肺部感染小鼠模型的治疗效果显著(P<0.01),对枯草芽孢杆菌感染小鼠具有显著的治疗效果(P<0.05),而对感染金黄色葡萄球菌的小鼠无明显影响。运用RT-PCR,研究β-内酰胺酶、溶血及毒力相关基因的表达,评价其抗菌机制。结果提示,2种药物联用于肺炎克雷伯菌的抗菌机制可能涉及上调或下调β-内酰胺酶相关基因(包括GES、VEB、PER-2和IMP),在枯草芽孢杆菌中抗菌机制可能涉及上调或下调溶血相关基因(yhdP、yhdT、yqhB和yugS);在金黄色葡萄球菌中,抗菌机制可能涉及上调或下调关键毒力基因(saeR、hla、sbi和mecA)。这些数据表明,TSH与NMT联合使用,通过调节β-内酰胺酶、溶血和毒力相关基因的转录水平表达,对3株菌株表现出显著的体外杀菌作用;并且该组合对体内感染肺炎克雷伯菌和枯草芽孢杆菌的小鼠模型具有更好的治疗作用。因此,TSH和NMT的联合治疗可能对细菌感染具有潜在的预防或治疗作用。
Tamsulosin hydrochloride(TSH)is a selectiveα_(1) adrenergic receptor antagonist used in the treatment of symptomatic benign prostatic hyperplasia(sBPH).Ningmitai capsule(NMT)is a traditional Chinese medicine preparation produced on the basis of traditional Chinese herbs formula.NMT is mainly used for treating stranguria caused by damp and hot accumulate knot,dripping wet acerbity pain and bloody urine,lower urinary tract infection and chronic prostatitis.It has been confirmed that TSH can be used in combination with many drugs to treat microbial infections and resistance to antibiotics,which displayed better therapeutic effect and application prospect.NMT also has obvious antibacterial and bactericidal effects on many pathogenic bacteria such as Escherichia coli,Proteus,Neisseria gonorrhoeae,Streptococcus faecalis,Staphylococcus aureus and so on.It is suggested that the combined application of these two drugs may have significant antibacterial activity against clinical bacteria.Therefore,anti-bacterial activities of combination of TSH and NMT were tested in vitro by turbidimetric assays.We found that combination use of TSH and NMT showed significant selectivity which displayed stronger inhibitory activities against the three strains than that of the application of single drug in vitro;The infective animal models were used to test the antibacterial activity of TSH combined with NMT in vivo.The results showed a potent effect(P<0.01)of combination use of two drugs on the treatment of pneumonic sepsis mouse infected with K.pneumonia and a significant effect(P<0.05)on the mouse infecting with B.subtilis,while the treatment had no obvious effects on the mouse infecting with S.aureus.And their antibacterial mechanisms were assessed by quantitation of the expression of functional genes in vitro using RT-PCR in response to infection by Klebsiella pneumonia(K.pneumonia),Staphylococcus aureus(S.aureus)and Bacillus subtilis(B.subtilis).The results suggest that the antibacterial mechanism of two drugs in combination might be attributed to the regulation ofβ-lactamase associated genes(including GES,VEB,PER-2 and IMP)in K.pneumonia,hemolysis associated genes(yhdP,yhdT,yqhB and yugS)in B.subtilis and key virulence genes(saeR,hla,sbi and mecA)in S.aureus.Taken together,these data suggested that combined use of TSH and NMT exhibited remarkable bactericidal effects in vitro to three strains through regulating the expression ofβ-lactamase,hemolysis and virulence associated genes at transcription level;The drug combination elicited better effects in the mouse model infecting with K.pneumonia and B.subtilis in vivo.Hence,the combination treatment of TSH and NMT may possess potential prophylactic or therapeutic effect against bacterial infections.