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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 combined antibacterial effect of ampicillin and subactam (AMP / SBT), the major active ingredient of Fritillaria pekinensis, in animal model of sepsis infection, And explore its possible mechanism of action. Methods: Forty SD rats were randomly divided into 4 groups: control group, model group, AMP / SBT, AMP / SBT + PM2, . Except for the blank control group, all groups were infected with multi-drug resistant Escherichia coli (ESBLs positive) through the tail vein and injected with the bacterial liquid for 1 h. The rats were injected with AMP / SBT466 mg.kg-1.d-1, intraperitoneally 1mL, twice a day; PM25.83mg.kg-1.d-1, 2mL daily gavage. Animal mortality, body weight, body temperature, general condition, white blood cell count and neutrophil ratio before and after administration, drug sensitivity test and pathological examination were observed within 96 hours. Results: The antibacterial effect of AMP / SBT + PM2 group was the best. Compared with the model group and the AMP / SBT group, the survival rate was higher (P <0.01, P <0.01) , White blood cell count was closer to normal (P <0.05, P <0.01), neutrophil classification was lower (P <0.01, P <0.01), and body weight did not change significantly. The blood bacterial elimination rate was higher in AMP / SBT + PM2 group than in AMP / SBT group (P <0.01). Susceptibility test of each group before drug administration showed that all of ampicillin were strictly drug-resistant. All of the blood culture-positive samples of AMP / SBT + PM2 group were all sensitive to ampicillin after administration. Conclusion: Compared with the single ampicillin sulbactam, the combination of cefotaxime and ampicillin sulbactam has stronger antibacterial effect in vivo. The antibacterial activity is confirmed by reversing bacterial resistance.