贝母素乙联合氨苄西林舒巴坦抗耐药菌感染的体内实验研究

Study on peiminine combined with ampicillin and sulbactam reversing drug-resistant infection in vivo

目的:观察浙贝母碱主要有效成分贝母素乙(peiminine,PM2)联合氨苄西林舒巴坦(优立新)(ampicillin and subactam,AMP/SBT),在败血症感染模型动物体内的联合抗菌作用,并试探讨其可能的作用机制。方法:SD大鼠40只,随机分成4组:空白对照组、模型组、氨苄西林舒巴坦组(AMP/SBT)、氨苄西林舒巴坦+贝母素乙组(AMP/SBT+PM2)。除空白对照组外,各组均以多药耐药大肠埃希氏菌(ESBLs阳性)尾静脉注射感染,注射菌液1h后给药,AMP/SBT466mg.kg-1.d-1,腹腔注射1mL,每日2次;PM25.83mg.kg-1.d-1,每日灌胃2mL。观察96h内动物死亡率、体质量、体温、一般状况、给药前后白细胞计数及中性粒细胞比例,药敏试验及病理学检查。结果:AMP/SBT+PM2组抗菌效果最佳,与模型组、AMP/SBT组比较,存活率更高(P<0.01,P<0.01),发热症状更轻(P<0.05,P<0.01),白细胞计数更接近正常(P<0.05,P<0.01),中性粒细胞分类较低(P<0.01,P<0.01),体重变化无统计学意义。血细菌消除率AMP/SBT+PM2组较AMP/SBT组高(P<0.01)。给药前各组药敏试验提示对氨苄西林均严格耐药,给药后AMP/SBT+PM2组血培养阳性的标本全部对氨苄西林转为敏感。结论:与单用氨苄西林舒巴坦相比,贝母素乙与氨苄西林舒巴坦联用,体内联合抗菌作用更强,药敏试验证实抗菌作用是通过逆转细菌耐药实现的。

Objective： To observe the antiseptic effect of peiminine combined with ampicillin sulbactam in vivo, and try to explore its possible mechanism. Methods：.40 SD rats were randomly divided into 4 groups： blank control group, model group, ampicillin sulbactam group （AMP/SBT）, ampicillin sulbactam ＋ Peiminine group （AMP/SBT＋PM2）. In addition to the blank control group, all groups were injected with multi-drug resistant E. coli though caudal vein to cause the rat sepsis model, lh later, drug administration began, AMP/SBT dose： 466mg/kg/d, intraperitoneal injection of lml, twice daily; PM2 daily dosage of 5.83mg/ kg, administered 2ml once a day. Record the animal mortality, body weight, body temperature, general condition, etc., white blood cell count and neutrophil percentage, drug susceptibility test. Results： AMP/SBT＋PM2 group won the best antibacterial effect, the general situation than the model group, AMP/SBT group is good, lighter pathological damage, higher survival rate （P〈0.01, P〈0.01）, lower body temperature （P〈0.05, P〈0.01）, lower white blood cell count （P〈0.05, P〈0.01）, low neutrophil （P〈0.01, P〈0.01）. Bacteria elimination rate AMP/SBT＋PM2 group, 80%, AMP/BT group, 30%, the difference was statistically significant （P〈0.01）. Susceptibility test in each group before administration prompted strictly resistant to ampicillin, after administration all blood culture-positive specimens of AMP/SBT＋PM2 group turn sensitive. Conclusions： Peiminine combined with ampicillin sulbactam using in vivo is more effective than ampicillin sulbactam alone. It is proven by drug susceptibility test that the effect is achieved by reversal of bacterial resistance.