黄连素在抑制幽门螺杆菌多重耐药中的作用研究  

Effect of berberine on inhibiting multi-drug resistance of Helicobacter pylori

作　　者：周帆 彭君伟 徐小青[3] 曹勤[3] ZHOU Fan;PENG Junwei;XU Xiaoqing;CAO Qin(Department of Gastroenterology,the Third People's Hospital of Huzhou,Huzhou 313000,China;不详)

机构地区：[1]湖州市第三人民医院消化内科,313000 [2]上海市闵行区肿瘤医院中西医结合科 [3]上海中医药大学附属普陀医院(上海市普陀区中心医院)消化内科

出　　处：《浙江医学》2024年第5期459-463,469,共6页Zhejiang Medical Journal

基　　金：国家自然科学基金资助项目(81603468);湖州市科学技术局公益性应用研究项目(2023GYB15)。

摘　　要：目的 研究黄连素抑制幽门螺杆菌(Hp)多重耐药(MDR)株对常用抗菌药物耐药性的作用。方法 采用E-test法检测临床分离Hp菌株的耐药性,从中筛选出双重耐药(DR)株和MDR株;通过抗菌药物浓度两倍递增法对DR株进行体外诱导耐药;采用倍比稀释法检测黄连素对MDR株的最小抑菌浓度(MIC);在黄连素1/2 MIC浓度下连续传代培养MDR菌株,分别在培养1代和5代后检测对应抗菌药物的MIC值变化。结果 (1)共成功分离出128株Hp菌株,根据药敏试验筛选出DR株30株,MDR株12株,阿莫西林(AMX)、左氧氟沙星(LEV)、克拉霉素(CLR)、甲硝唑(MTZ)的耐药率分别为4.7%、26.6%、32.0%、64.8%,分离株中的MDR率为9.4%。(2)体外成功诱导MDR株24株,AMX诱导失败,其中MTZ诱导株的耐药水平最高,CLR次之,LEV最低;(3)黄连素对36株MDR株有明显的抑菌作用,MIC值范围为8~128μg/mL,大部分集中在32μg/mL;(4)选取的27株高水平耐药MDR株,经黄连素作用后共有17株的MIC值降低4倍及以上或逆转为敏感株,其中分别有9株、11株、5株对应CLR、LEV、MTZ的MIC值有阳性变化。在3种抗菌药物的阳性株中,MTZ组的MIC值下降倍数最高,CLR组居中,LEV组最低,3组比较差异有统计学意义(P<0.05)。结论 黄连素可有效逆转部分MDR株对常用抗菌药物的耐药性,且逆转程度与作用时间、抗菌药物种类有关。Objective To study the effect of berberine on inhibiting Helicobacter pylori(Hp) multi-drug resistant(MDR) strains that are resistant to common antibiotics.Methods E-test was used to detect the drug resistance of clinical isolates,and double-drug resistant(DR) strains and MDR strains were screened.Then the DR strains were induced to MDR strains in vitro by two-fold increasing of antibiotic concentration method.The minimum inhibitory concentration(MIC) of berberine against MDR strains was detected by agar two-fold dilution method.The MDR strains were cultured continuously at1/2 MIC concentration of berberine in liquid,and the MIC values of corresponding antibiotics were detected by E-test after one and five generations,respectively.Results(1) One hundred and twenty-eight Hp strains were isolated,including thirty DR strains and twelve MDR strains according to the drug susceptibility test.The drug resistance rates of Hp to amoxicillin(AMX),levofloxacin(LEV),clarithromycin(CLR) and metronidazole(MTZ) were 4.7%,26.6%,32.0% and 64.8%,and MDR rate in isolated strains was 9.4%.(2) There were 24 MDR strains induced in vitro successfully.Strains induced by AMX were failed.The resistance level of induced strains by MTZ was the highest,followed by those of CLR and LEV.(3) Berberine could significantly inhibit the growth of the 36 MDR strains,MIC values of which vary from 8 μg/mL to 128 μg/mL,mostly at 32 μg/mL.(4) Of the 27 MDR strains selected with high-level resistance,the MIC values of 17 strains were reduced by more than four times or reversed into sensitive strains after berberine treatment,among which,9,11 and 5 strains showed positive changes in MIC values corresponding to CLR,LEV and MTZ,respectively.Among the positive strains of three antibiotics,the median decline multiple of MIC value was the highest in MTZ group,followed by CLR group and LEV group,and the difference among the three groups was statistically significant(P<0.05).Conclusion Berberine can effectively reverse resistance of some MDR strains to common

关 键 词：黄连素 幽门螺杆菌 多重耐药 

分 类 号：R285[医药卫生—中药学]