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目的研究拉莫三嗪(LTG)对缺氧缺血性脑损伤(HIBD)新生大鼠的神经保护作用,以及不同用药剂量和用药时间对该作用的影响。方法7日龄SD大鼠126只,除假手术组(14只)外均行左侧颈总动脉离断并置入密闭缺氧箱,制备HIBD动物模型。LTG治疗A组(56只)术后3h分别给予LTG5、10、20、40mg/kg,治疗B组(42只)术前1h和术后3、6h给予LTG20mg/kg腹腔注射,缺血缺氧组(14只)无治疗。用酶标法、免疫组化和原位末端标记(TUNEL)法,分别检测HIBD24h后血清神经元特异性烯醇化酶(NSE)浓度、大脑皮层NSE阳性细胞数以及大脑皮层和齿状回TUNEL阳性细胞数。结果与缺氧缺血组比较,10、20、40mg/kg LTG组TUNEL阳性细胞数显著减少;20mg/kg和40mg/kg LTG治疗组血清NSE的浓度显著降低[缺血缺氧组:(103·3±3·3)μg/ml,20mg/kg组:(51·2±2·5)μg/ml,40mg/kg组:(32·4±1·7)μg/ml],皮层NSE阳性细胞数则显著增高,40mg/kg组(78·3±6·5)比20mg/kg组(63·4±6·6)改变更显著。术前1h与术后3、6h给药组的血清NSE的浓度均显著降低,NSE及TUNEL阳性细胞数均显著性增高,术前1h组改变较术后3、6h给药组显著,3h与6h给药组间差异无统计学意义。结论LTG对HIBD新生大鼠可产生神经保护作用,作用疗效与用药时间和剂量有关。
Objective To investigate the neuroprotective effects of lamotrigine (LTG) on neonatal rats with hypoxic-ischemic brain damage (HIBD) and the effects of different dosages and time of administration on this effect. Methods Totally 126 SD rats of 7-day-old were divided into sham-operated hypoxia chamber except for the sham-operation group (14 rats). The HIBD animal model was established. LTG group A (n = 6) received LTG 5, 10, 20, and 40 mg / kg at 3 h postoperatively, and group B (n = 42) received LTG 20 mg / Group (14) without treatment. Serum neuron-specific enolase (NSE) concentration, NSE-positive cells in cerebral cortex and TUNEL positive in cerebral cortex and dentate gyrus were detected by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry and TUNEL method Cell number. Results Compared with hypoxia-ischemia group, the number of TUNEL positive cells in 10, 20, 40 mg / kg LTG group was significantly decreased; while the serum NSE concentrations in 20 mg / kg and 40 mg / kg LTG treatment group were significantly decreased · 3 ± 3 · 3) μg / ml, 20 mg / kg group: (51 · 2 ± 2.5) μg / ml and 40 mg / kg group: (32.4 ± 1.7 · μg / ml) The number of positive cells was significantly higher in the 40mg / kg group (78.3 ± 6.5) than in the 20mg / kg group (63.4 ± 6.6). The concentrations of NSE in NSC and TUNEL positive cells were significantly decreased at 1h before operation and 3h and 6h after operation. The number of NSE and TUNEL positive cells increased significantly at 1h before operation and 3h and 6h after operation There was no significant difference between 6h administration groups. CONCLUSION: LTG can produce neuroprotective effect on neonatal HIBD rats. The effect of LTG is related to the time and dose of administration.