改变奥扎格雷钠碱基对大鼠肝微粒体蛋白浓度和CYP450酶含量的影响

目的 改变奥扎格雷钠碱基为氨丁三醇后,研究药物对大鼠肝药酶的影响.方法 将健康SD大鼠分为7组(n=6),分别静脉注射给予高、中、低剂量的奥扎格雷氨丁三醇和奥扎格雷钠,并设定空白对照组,连续给药7d,于末次给药24 h后处死大鼠,取肝脏,制备肝微粒体.采用紫外-可见分光光度法测定大鼠肝微粒体蛋白的浓度和CYP 450酶的含量.结果 高、中、低剂量奥扎格雷氨丁三醇组大鼠的肝微粒体蛋白浓度均值分别为10.14±1.44、10.28±1.01、8.10±1.85 mg·mL-1,高、中、低剂量奥扎格雷钠组的肝微粒体蛋白浓度均值分别8.26--±1.55、8.19±0.49、8.72±1.76 mg· mL-1,与空白对照组比较,差异均无统计学意义.高、中、低剂量奥扎格雷氨丁三醇组大鼠的CYP 450酶含量分别为0.537±0.075、0.454±0.106、0.498±0.071 μmol·g-1,高、中、低剂量奥扎格雷钠组的CYP 450酶含量分别为0.504±0.092、0.450±0.086、0.476±0.028μmol·g-1,与空白对照组比较,差异均无统计学意义.结论 改变奥扎格雷钠碱基为氨丁三醇后,多剂量静脉给予大鼠奥扎格雷氨丁三醇后,其肝微粒体蛋白浓度和CYP 450酶的含量与奥扎格雷钠组及空白对照组相比,差异均无统计学意义.预测奥扎格雷改变碱基为氨丁三醇后对大鼠肝药酶无明显影响.

Effect of changing the basic group of Ozagrel on liver microsomal protein concentration and the content of CYP450 in rats

OBJECTIVE To investigate the effect on liver microsomal cytochrome system in rat after changing the basic group of sodium ozagrel to tromethamine.METHODS Rats were devoted into 7 groups (n =6),including high dosage group,mid dosage group and low dosage group of sodium ozagrel and tromethamine ozagrel,and also a blank control group.The rats were treated with sodium ozagrel and tromethamine ozagrel by intravenous injection,once daily for 7 days.Then the content of liver microsomal protein and CYP450 of rat were determined by ultraviolet-visible spectrophotometer.RESULTS Protein concentration of liver microsomal of tromethamine ozagrel group was 10.14 ± 1.44 mg· mL-1,10.28 ± 1.01 mg· mL-1 and 8.10 ± 1.85 mg· mL-1,respectively.Protein concentration of liver microsomal of sodium ozagrel group was 8.26 ± 1.55 mg·mL-1,8.19 ±0.49 mg·mL-1 and 8.72 ± 1.76 mg· mL-1,respectively.The content of CYP450 of tromethamine ozagrel group was 0.537 ± 0.075 μmol· g-1,0.454-0.106 μmol· g-1 and 0.498 ± 0.071 μmol· g-1,respectively.The content of CYP450 of sodium ozagrel group was 0.504 ± 0.092 μ mol· g-1,0.450 ± 0.086 μmol· g-1 and 0.476-0.028 μmol· g-1,respectively.Compared with the control group,there were no statistically significant difference on the protein concentration of liver microsomal and the content of CYP450.CONCLUSION After changing the basic group of sodium ozagrel to tromethamine,the protein concentration of liver microsomal and the content of CYP450 in the rat by intravenous injection of tromethamine ozagrel has no statistically significant difference when compared with the sodium ozagrel group and control group.According to these,we predict that changing the basic group of sodium ozagrel to tromethamine has no significant effect on liver microsomal cytochrome system in rat.