μ型阿片肽受体对癫痫敏感大鼠海马γ-氨基丁酸神经元影响

Effects of mu-opioid receptors on hippocampal GABAergic neurons in the rats with seizure susceptibility

目的探讨μ型阿片肽受体(MORs)介导大鼠癫痫敏感性形成过程中海马γ-氨基丁酸(GABA)神经元的变化。方法红藻氨酸(KA)皮下注射建立大鼠癫痫发作模型,采用脑立体定位及微渗透泵技术,海马内微量注射MORs激动剂吗啡感受素(PL017)或拮抗剂β-呋纳曲胺(β-FNA)。7 d后通过阈下剂量KA检测大鼠癫痫发作敏感性,应用免疫组织化学方法观察海马齿状回及门区GABA神经元数目和灰度变化。结果 KA诱导癫痫敏感性形成大鼠的海马齿状回及门区GABA神经元数目明显减少,染色强度减低。PL017可进一步减少海马齿状回及门区GABA神经元数目及其染色强度,而β-FNA能够明显改善KA及PL017对GABA神经元的损伤作用。结论 MORs介导癫痫发作敏感性形成机制与海马齿状回及门区GABA神经元损伤有关。

Objective To investigate the change of hippocampal GABAergic neurons in the rats with seizure susceptibility mediated by mu-opioid receptors（ MORs）. Methods The SD rats were injected subcutaneously with a convulsive dose（ 10 mg / kg） of kainic acid（ KA）. Normal saline（ NS）,selective MORs antagonist β-FNA or selective MORs agonist PL017 were infused constantly into ventral hippocampus of awakened and freely moving animals for 7 days by mini-osmotic pumps. After 7 days,all rats were given subcutaneously with subconvulsant dose of KA（ 5 mg / kg） to determine the situation of seizure susceptibility. Then the numbers and gray values of immunohistochemical positive GABAergic neurons in hippocampal dentate gyrus granule cells（ DGCs） and hilus were detected by image analysis system. Results The number and staining density of GABA positive neurons in DGCs and hilus were decreased significantly in KA ＋ NS group. PL017 deteriorated the KA induced decrease of GABAergic neurons both in number and staining density. Butβ-FNA could reverse the effects of KA and PL017 on GABA neurons in DGCs and hilus. Conclusion The results indicated that the seizure susceptibility of rats mediated by MORs was related to the down-regulation of GABAergic neurons in hippocampal DGCs and hilus.