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-  2016 

高压氧对顺铂在脑胶质瘤大鼠体内药代动力学的影

Keywords: 高压氧 顺铂 血脑屏障 脑胶质瘤
Hyperbaric oxygen Glioma Blood brain barrier Cisplatin

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Abstract:

目的观察高压氧(HBO)对顺铂在脑胶质瘤大鼠体内药代动力学的影响。 方法建立SD大鼠C6细胞脑胶质瘤模型,14d后,选取84只造模成功大鼠,按照随机数字表法分为对照组和HBO组,每组42只。2组大鼠均经尾静脉注射顺铂1mg/kg,每日1次,连续7d;HBO组于每次顺铂注射后进行HBO治疗,对照组常压常氧下活动。第7天于顺铂注射后不同时间点(5min、10min、30min、1h、2h、4h、8h)每时间点取6只大鼠,采集血液、脑脊液及脑瘤组织;高效液相色谱法测定顺铂浓度,应用3P97药物代谢动力学程序拟合药物代谢动力学参数,并进行统计学比较分析。 结果2组大鼠血液顺铂峰浓度(Cmax)、消除半衰期(T1/2)、药物浓度-时间曲线下面积(AUC0→8h)比较,差异均统计学意义(P>0.05)。与对照组比较,HBO组大鼠脑脊液顺铂浓度于5min~2h之间显著增加,差异有统计学意义(P<0.05);对照组Cmax、T1/2、AUC0→8h分别为(9.52±1.65)μg/ml、(0.81±0.13)h、(9.31±0.71)mg?min?L-1,HBO组Cmax、T1/2、AUC0→8h分别为(2.38±0.15)μg/ml、(2.18±0.17)h、(4.12±0.42)mg?min?L-1,明显高于对照组,差异有统计学意义(P<0.05)。与对照组比较,HBO组大鼠瘤组织顺铂浓度于5min~8h之间显著增加,差异有统计学意义(P<0.01);Cmax、T1/2、AUC0→8h分别为(2.14±0.16)μg/ml、(3.16±0.65)h、(6.28±0.98)mg?min?L-1,明显高于对照组,差异有统计学意义(P<0.01)。 结论HBO可增加顺铂在C6脑胶质瘤模型大鼠脑组织中的分布,并延长其在脑瘤组织的消除半衰期。
Objective To observe the effect of hyperbaric oxygen (HBO) on the pharmacokinetics of cisplatin in rats modelling brain glioma. MethodsA model of brain glioma was introduced successfully into each of 84 adult male Sprague-Dawley rats through injecting C6 cells. Fourteen days later they were randomly divided into a control group and an HBO group, each of 42. Both groups were given intravenous cisplatin injections (1 mg/kg) daily for 7 days. The HBO group was additionally given HBO therapy every day after the injection of cisplatin. On the 7th day, the blood, cerebrospinal fluid and tumor tissues of 6 rats from each group were collected 5 min, 10 min, 30 min, 1 h, 2 h, 4 h and 8 h after the last injection. The concentrations of cisplatin were measured using high performance liquid chromatography, and the data were analyzed using the 3P97 program of pharmacokinetics. ResultsThere was no significant difference between the two groups in the peak cisplatin concentration (Cmax), terminal half life time (T1/2) and the area under the drug concentration-time curve (AUC0→8h). Compared with the control group, the average cisplatin concentration in the cerebrospinal fluid of the HBO group increased significantly more from 5 min to 2 h after the last injection. Compared with the control group, the average cisplatin concentration in the tumorous tissues of the HBO group increased significantly more from 5 min to 8 h after the last injection. ConclusionsHBO can promote the distribution of cisplatin in the brain in response to glioma and prolong its half-life in tumorous brain tissue

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