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目的:研究低频脉冲超声治疗的起始时间对载万古霉素骨水泥的药物动力学、药效释放以及抗菌活性的影响。方法:选择50只健康大鼠,在大鼠髋关节均植入载万古霉素的骨水泥以及标准金黄色葡萄球菌(ATCC13565,中国生物鉴定研究所),随后将50只大鼠随机分成观察组、对照组,观察组在植入后12 h进行低频超声治疗,对照组在植入后30 min进行低频超声治疗,两组均治疗12 h后取4只大鼠测定髋关节内的渗血量,其余大鼠测定髋关节内的药物浓度,计算药物动力及药效参数,在植入48 h后计数髋关节腔内的活菌量并进行组间比较。结果:观察组、对照组均在植入3 h后达到药物浓度高峰,对照组3 h后药物浓度呈明显的下降态势,并在14 h后下降到MIC以下,观察组在3 h后也呈下降态势,但在12 h采用低频超声治疗后,药物浓度再次上升,并一直持续在MIC以上至第34小时;观察组Cmax/MIC(5.58±1.86)明显低于对照组的(14.81±2.41),差异具有统计学意义(P<0.05);观察组T>mic(35.08±5.98)h明显高于对照组的(13.49±1.49)h,差异具有统计学意义(P<0.05);对照组菌落数、渗血量明显高于观察组(P<0.05)。结论:与植入后立即进行超声治疗相比,在第12小时进行治疗能够有效提高血液的T>mic,提高载万古霉素骨水泥的抗菌作用。
Objective: To study the effect of low-frequency pulsed ultrasound on the pharmacokinetics, drug release and antibacterial activity of vancomycin-loaded cements. Methods: Fifty healthy rats were selected. Osteomycin-loaded bone cement and standard Staphylococcus aureus (ATCC13565, China Institute of Biologics) were implanted into the hip joint of rats, then 50 rats were randomly divided into observation group , The control group and the observation group were treated with low-frequency ultrasound 12 h after implantation, while the control group was treated with low-frequency ultrasound 30 min after implantation. After 12 h of treatment, 4 rats were used to measure the amount of oozing blood in the hip joint , The remaining rats were measured in the hip joint drug concentration, pharmacokinetic and pharmacodynamic parameters were calculated, the amount of viable bacteria in the hip cavity was counted 48 h after implantation and compared between groups. Results: In the observation group and the control group, the peak of drug concentration reached the peak after 3 hours of implantation. The drug concentration in the control group decreased significantly after 3 hours and dropped below the MIC level after 14 hours. The observation group also appeared after 3 hours However, after 12 h treatment with low-frequency ultrasound, the drug concentration increased again and continued from the MIC to the 34th hour. The Cmax / MIC (5.58 ± 1.86) in the observation group was significantly lower than that in the control group (14.81 ± 2.41) (P <0.05). The T> mic (35.08 ± 5.98) h in the observation group was significantly higher than that in the control group (13.49 ± 1.49) h, the difference was statistically significant (P <0.05) Number of oozing blood was significantly higher than the observation group (P <0.05). CONCLUSION: Compared with ultrasound treatment immediately after implantation, treatment at 12 hours can effectively increase blood T> mic and improve the antibacterial effect of vancomycin-containing cement.