目的探讨胞磷胆碱(cytidine 5’-diphosphocholine,CDPC)经脑间质途径预防性治疗脑缺血的有效剂量范围。方法实验对象为56只成年雄性SD大鼠,随机分为7组,分别为对照组(尾状核中心注射生理盐水5μl),腹腔组(腹腔注射CDPC 2 g/kg),实验组1~5(尾状核中心注射CDPC 5μl,浓度分别为25、40、50、60和75 mmol/L)。按上述分组预防性给药2h后,采用永久性大脑中动脉栓塞(permanent middle cerebral artery occlusion,pMCAO)模型模拟脑缺血过程,并应用梗死体积比的测量比较各组间的治疗效果差异。结果应用简单扩散给药(simple diffusion delivery,SDD)方式脑内直接微量注射CDPC的最佳有效保护浓度为50 mmol/L(实验组3,梗死体积比为4.1%±2.0%),实验组2与实验组4的梗死体积比分别为8.1%±4.1%和8.7%±2.4%,以上3组与对照组27.7%±10.5%相比均有统计学差异(P均=0.000)。结论经尾状核预防性微创给药治疗脑缺血的有效浓度范围为40~60 mmol/L。
Objective To investigate the effective dose range of cytidine 5' -diphosphoeholine (CDPC) for cerebra] ischemia by micropuneture injection via the brain interstitial route. Methods Totally 56 adult male Sprague Dawley (SD) rats were enrolled in this study. The rats were randomly divided into 7 groups : control group ( 5μl saline was injected into the caudate nucleus ), intraperitoneal group (2 g/kg CDPC was injected into the peritoneal cavity) , and experimental groups 1 -5 (5 μl CDPC was injected into the caudate nucleus at a dosage of 25, 40, 50, 60 and 75 mmol/L,respectively). Two hours after the preventive administration, permanent middle cerebral artery occlusion (pMCAO) was made to simulate the process of cerebral ischemia, and the infarct volume of each group was assessed. Results With simple diffusion delivery (SDD), the most effective protective concentration of CDPC was 50 mmol/L (experimental group 3, infarct volume ratio: 4. 1% ± 2.0% ). The infarct volume ratio in the experimental groups 2 (8.1% ± 4.1% ), 3 and 4 (8.7% ± 2.4% ) was all significantly lower than that in the control (27.7% ± 10.5% , all P = 0. 000). Conclusion For cerebral ischemia, the effective dose rage for micropuncture injection of CDPC via the brain interstitial route was 40 - 60 mmol/L.