海马μ型阿片受体在红藻氨酸诱导的癫痫敏感性形成中的作用

The role of mu-opioid receptors in seizure susceptibility induced by kainic acid

目的 探讨海马 μ型阿片受体 (MORs)在红藻氨酸 (KA)诱导的癫痫敏感性形成机制中的作用。方法 惊厥剂量KA(10mg/kg)皮下注射诱导大鼠癫痫发作 ,应用微渗透泵技术在大鼠腹侧海马连续注射MOR激动剂PL0 17和拮抗剂 β FNA。 1周后 ,皮下注射阈下剂量KA (5mg/kg)进行癫痫发作敏感性检测。结果 注射阈下剂量KA后 ,PL0 17+KA组 10 0 0 %出现 4级以上发作 ,而 β FNA+KA组只有 2 8 6 %。PL0 17+KA组潜伏期为 (10 1± 3 0 )min ,明显短于KA组和人工脑脊液 +KA组(0 0 1<P <0 0 5 ) ;β FNA +KA组的潜伏期为 (4 5 6± 10 9)min ,与其他各组比较差异有显著意义 (P <0 0 1)。β FNA +KA组发作级别为 1 7± 0 1,显著低于KA、人工脑脊液 +KA和PL0 17+KA组 (P <0 0 1)。结论 海马MORs及阿片肽参与了癫痫发作敏感性的形成机制。

Objective To investigate the role of hippocampal mu-opioid receptors (MORs) in the formation of seizure susceptibility induced by kainic acid (KA). Methods The SD rats were injected subcutaneously with a convulsive dose of KA (10 mg/kg). Then mini-osmotic pumps were used for intrahippocampal injection with a selective MOR antagonist β-FNA, and a selective MOR agonist PL017 in these rats. 7 days later, the seizure susceptibility was checked by a subthreshold dose of KA (5 mg/kg). Results All animals showed motor seizures over Stage 4 after a convulsive dose KA injection. 7 days later, 100% animals showed seizures over Stage 4 in KA, CSF + KA and PL017+KA groups after injection of subthreshold dose of KA, but only 28.5% in PL017+KA group. Mean latency of PL017+KA group was (10.1±3.0) minutes, shorter significantly than that of KA and CSF+KA groups (0.01< P <0.05). Mean latency of β-FNA+KA group was (45.6±10.9) minutes, more prolonged significantly as compared with other groups ( P <0.01). The mean seizure stages induced by subthreshold dose of KA in PL017 + KA group were 4.7±0.5, showing no significant differences compared with KA and CSF + KA groups ( P >0.05). The mean stage of β-FNA + KA group was 1.7±0.1, being reduced significantly as compared with the stages of other three groups ( P <0.01). Conclusions The results showed that activation or inhibition of hippocampal MORs could promote or decrease the severity of seizures induced by subthreshold dose of KA, suggesting that there remains the involving of MORs in formation of seizure susceptibility induced by KA.