PEG化青霉素降低红细胞溶血的研究

Study on reducing hemolysis by PEGylated penicillin

目的采集葡萄糖-6-磷酸脱氢酶(G6PD)缺陷的动物模型血液,评价PEG化青霉素降低红细胞溶血的作用。方法 1%乙酰苯肼皮下注射大鼠制备G6PD缺陷的动物模型,取其红细胞制成混悬液,比较青霉素和PEG化青霉素的溶血作用,以及两组的红细胞脆性、红细胞膜流动性。结果青霉素组出现明显的红细胞溶血,且随着浓度变化和孵育时间延长溶血具有增加的趋势,溶血率高达25%,而PEG化青霉素组未见明显溶血;另外,红细胞脆性实验结果表明,PEG化青霉素对红细胞膜的作用非常轻微,H50%为43.6%,显著低于青霉素组(52.9%);红细胞膜流动性结果表明,PEG化青霉素对红细胞膜的流动性影响非常轻微。结论 PEG化青霉素的溶血率较低,为该药的体内研究和进一步新型药物制剂开发奠定基础。

Objective To analyze the effects of PEGylated penicillin（PEG-PEN） on reducing hemolytic via the glucose-6-phosphate dehydrogenase（G6PD）-deficient rats＇ blood.Methods The rat model with G6PD-deficiency was established via sc injecting 1%acetylphenyl-hydrazine.Then the G6PD-deficient erythrocyte suspension obtained from the rat model was used to evaluate the hemolytic effects of PEN and PEG-PEN by detecting the hemolytic activity,erythrocyte osmotic fragility and membrane fluidity of erythrocytes.Results It was found that PEN could cause serious hemolysis to the erythrocyte suspension with the increase of drug concentration and the prolongation of drug incubation time,the hemolytic rate of PEN was up to 25%,while no significant hemolysis was found in PEG-PEN group.Additionally,the result of erythrocyte osmotic fragility indicated that PEG-PEN exerted a slight effect on the erythrocyte membranes,the H_（50%） was much less than that of PEN（43.6%vs.52.9%）.Erythrocyte membrane fluidity indicated that the effect of PEG-PEN on erythrocyte membrane fluidity was very slight Conclusion PEG-PEN plays an important role in reducing the side effect of hemolysis induced by PEN.The low hemolytic activity of PEG-PEN makes it a favorable candidate for in vivo tests and PEG-PEN could also provide useful insight for the further formulation development as an innovative drug.