甘珀酸对戊四氮点燃癫癎大鼠海马Fos NMDAR2 GFAP表达的影响

Effect of carbenoxolone on expression of Fos, NMDAR2 and GFAP in the hippocampus of pentylenetetrazo-kindled epileptic rats

摘要:

目的：缝隙连接（GJ）是细胞间直接通道，对同步化放电有重要作用。该研究旨在探讨GJ阻断剂甘珀酸（CBX）对戊四氮（PTZ）点燃大鼠癫癎样活动的影响。方法：30只SD雄性大鼠随机分为3组：对照组（NS组），点燃组（K组），干预组（CBX组），每组10只大鼠。NS组每日腹腔注射生理盐水；K组和CBX组大鼠每日腹腔注射PTZ（35 mg/kg）至点燃，再分别腹腔注射生理盐水、CBX（10 mg/kg）干预 3 d。观察3组大鼠惊厥行为的变化，以及免疫组化染色方法观察Fos、NMDAR2、GFAP在海马内的表达变化。结果：①PTZ点燃癫癎大鼠出现自发性抽搐，自发性抽搐次数K组>CBX组>NS组（P<0.05）。②点燃癫癎大鼠海马Fos-Li神经元、NMDAR2-Li神经元增多，GFAP-Li星形胶质细胞增多，胞体肥大，突起丰富。CBX干预后，Fos-Li、NMDAR2-Li神经元减少（P<0.05, P<0.01），GFAP-Li星形胶质细胞无明显改变（P>0.05）。结论：CBX抑制自发性抽搐和神经元活动，CBX有潜在的抗惊厥或协助抗惊厥的作用。［中国当代儿科杂志，2007，9（5）：465-468］

Abstract:

OBJECTIVE: Gap junctions, the clusters of intercellular channels, play an important role in synchronizing electrical activity. This study investigated the effect of gap junction blocker carbenoxolone (CBX) on epileptic activity in pentylenetetrazo (PTZ)-kindled rats. METHODS: Thirty adult male SD rats were randomly divided into three groups: control, PTZ-kindled and CBX-treated groups (n=10 each). The rats from the PTZ-kindled and the CBX-treated groups were intraperitoneally injected with PTZ (35 mg/kg.d) to induce epilepsy. After epilepsy kindling, they were intraperitoneally injected for 3 days with CBX (10 mg/kg) (CBX-treated group) or with normal saline (PTZ-kindled group). The control group received intraperitoneal injections of normal saline. Anti-GFAP, anti-Fos, and anti-NMDARZ immunohistochemical ABC methods were used to detect the expression of GFAP-Li, Fos-Li and NMDAR2-Li in the hippocampus respectively. RESULTS: Spontaneous seizures occurred in PTZ-kindled epileptic rats. CBX administration reduced spontaneous seizures. The NMDAR2-Li and Fos-Li neurons as well as GFAP-Li astrocytes in hippocampi increased in PTZ-kindled epileptic rats compared with controls. The numbers of Fos-Li (93.75±7.94 vs 165.25 ±15.87, P< 0.05) and NMDAR2-Li neurons (61.47±3.62 vs 148.72±14.53, P< 0.01) in the CBX-treated group were significantly less than in the PTZ-kindled group. There were no significant differences in the GFAP-Li expression between the CBX-treated and the PTZ-kindled groups. CONCLUSIONS: CBX may inhibit spontaneous seizures and decrease the numbers of Fos-Li and NMDARZ-Li neurons, thus providing anti-epileptic effects.