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目的探讨新型抗癫痫药物妥泰(TPM)口服和腹腔注射两种给药途径对缺氧缺血性脑损伤(HIBD)新生大鼠的脑保护作用。方法120只生后7日龄Wistar大鼠随机分为假手术组(24只)、单纯缺氧缺血组、TPM口服给药组、TPM腹腔注射给药组(各32只),两种途径均在缺氧缺血前后给药妥泰剂量分别为缺氧缺血前150mg/kg,缺氧缺血后即刻每间隔12h给药1次,每次100mg/kg,持续5d。口服及腹腔给药剂量相同,妥泰首剂150mg/kg,以后100mg/kg,12h1次,至研究日。通过建立新生大鼠HIBD模型,应用HE染色、免疫组织化学及Western-Blotting等方法,观察HIBD后各组脑组织病理学改变及大脑皮质胶质细胞源性神经营养因子(GDNF)表达的动态变化,探讨TPM不同给药途径对脑损伤的保护作用。结果TPM两种给药途径均能明显减轻脑组织损伤;GDNF的表达于术后12h开始上升,第3天达高峰,第5天有所降低但仍处于较高水平;两种途径给药组GDNF的表达比单纯缺氧缺血组各时间点明显增加,差异有统计学意义(P<0.05);GDNF的表达在两种途径给药各时间点上差异无统计学意义(P>0.05)。结论HIBD后GDNF表达随时间而变化,于损伤后第3天达最高水平;两种途径给药对GDNF表达无明显影响,均可发挥较好的脑保护作用;TPM脑保护作用机制可能通过增加胶质细胞分泌GDNF而实现。
OBJECTIVE: To investigate the protective effect of TPA on rats with hypoxic-ischemic brain damage (HIBD). Methods 120 Wistar rats of 7 days after birth were randomly divided into sham-operation group (24 rats), hypoxia-ischemia group, TPM oral administration group and TPM intraperitoneal injection group (32 rats each) Both topiramate doses before and after hypoxic-ischemic preconditioning were 150mg / kg before hypoxia and ischemia, and once every 12h after hypoxic-ischemic insult, each 100mg / kg for 5 days. Oral and intraperitoneal doses of the same dose of Topiramate 150mg / kg, after 100mg / kg, 12h1 times, to the study day. HIBD model of neonatal rats was established. The changes of brain tissue pathology and the expression of glial cell line-derived neurotrophic factor (GDNF) in each group were observed by HE staining, immunohistochemistry and Western-Blotting. To explore the protective effect of different routes of administration of TPM on brain injury. Results The administration of TPM significantly reduced brain injury. The expression of GDNF began to rise at 12h after operation and peaked on the third day, but decreased at the fifth day. The levels of GDNF were still high at the fifth day. The expression of GDNF was significantly increased at each time point compared with that of hypoxia-ischemia group only (P <0.05). There was no significant difference in the expression of GDNF between the two routes of administration (P> 0.05) . Conclusion The expression of GDNF after HIBD changes with time and reaches the highest level on the third day after injury. Both of the two routes have no obvious effect on the expression of GDNF, which can exert better brain protection. The protective mechanism of TPM may be increased by increasing GDNF secretion of glial cells and achieve.