猪眼动脉灌注卡铂与洛铂药代动力学及对眼组织损伤的实验研究

Pharmacokinetics and injury to eye tissue of intra-arterial(ophthalmic artery)chemotherapy of carboplatin and lobaplatin in porcine

目的拟对西藏小型猪经眼动脉分别灌注卡铂和洛铂,研究其药代动力学以及对猪眼组织的损伤程度。方法将10只西藏小型猪平均分为A(卡铂组)、B(洛铂组)两组,将卡铂30 mg或洛铂3 mg分别用5%葡萄糖注射液30 mL稀释后经猪脑膜中动脉灌注至眼动脉。药物灌注后,分别于术后0.5 h、1 h、2 h、2.5 h、3 h、3.5 h以及4 h共7个时间点于股动脉取2 mL血液置入EDTA-抗凝紫头管,离心留取血浆,用于检测样品的药物浓度。采血样结束后处死实验猪,取双侧眼球及视神经组织,10%中性甲醛缓冲液固定后行病理HE染色,观察视网膜细胞、视神经细胞以及血管壁形态、周围炎性细胞浸润情况。结果A、B组各一只实验猪因穿刺不成功未完成实验,余8只均完成全程实验。卡铂组和洛铂组血液药物浓度随时间点快速下降,给药后3~4 h血液浓度下降趋于平缓。洛铂组药物浓度曲线起始段较卡铂组“陡”。卡铂组与洛铂组经眼动脉灌注术后两组猪视网膜细胞均形态正常,未见细胞溶解或核固缩;视网膜小动脉血管壁完整、内皮细胞形态正常,周围未见明显炎性细胞浸润。两组视神经细胞形态均未见异常。结论经猪眼动脉灌注洛铂与卡铂相比,其药物代谢更快,而且未见眼组织和视神经的损伤。本研究对眼组织损伤未设置时间点和灌注次数的对比,因此还需要进一步的研究。

Objective To evaluate the pharmacokinetics and injury to eye tissue of intra-arterialophthalmic artery chemotherapy of carboplatin and lobaplatin in a normal porcine model.Methods Ten Tibetan minipigs were divided into two groups:A(carboplatin)group and B(lobetoplatin)group equally.Each pig received a single dose of either 30 mg of carboplatin(group A)or 3 mg of lobaplatin(group B)by middle meningeal artery injection into the ophthalmic artery.After the drug infusion,2 ml of blood was taken from the femoral artery and placed in EDTA-anticoagulant purple tube at the time of 0.5 hour,1 hour,2 hours,2.5 hours,3 hours,3.5 hours,and 4 hours after operation.The plasma is collected by centrifugation to detect the drug concentration of the sample.After the blood samples were taken,the experimental pigs were sacrificed and the bilateral eyeballs and optic nerve tissues were taken.After 10%neutral formaldehyde buffer was fixed,pathological HE staining was performed to observe the morphological changes of retinal cells and optic nerve cells.Results One pig died in each group A and B,and the remaining 8 pigs completed the entire experiment.The blood drug concentrations in the carboplatin group and lobaplatin group rapidly decreased with time,and the blood concentration decreased gradually from 3 hours to 4 hours after administration.The initial phase of the drug concentration curve in the lobaplatin group was“steeper”than the carboplatin group.The retinal cell morphology was normal in both groups after ophthalmic artery instillation,and there was no cell lysis or nuclear pyknosis.The morphology of retinal arteriole endothelial cells was normal.There were no abnormalities in the morphology of the optic nerve cells in both groups.Conclusions Compared with carboplatin,the drug metabolism of lobaplatin injected through the middle meningeal artery into the ophthalmic artery of pigs was faster.There was no damage to the eye tissue and optic nerve in both groups.However,there are still deficiencies in this study,so it is still necessary to further research.