目的探讨在戊四氮(PTZ)诱发的癫痫动物模型中,石菖蒲及其主要成分α-细辛醚对海马区神经元N-甲基-D-天冬氨酸受体1(NMDAR1) mRNA表达水平的影响。方法3周龄Wistar幼鼠ipPTZ60mg/kg建立癫痫模型。动物模型随机分为模型对照组、石菖蒲组、α-细辛醚组,另设正常对照组。各组均ig给药。正常对照组给予生理盐水1.0mL/d,其余各组分别给予石菖蒲2350mg/(kg·d),α-细辛醚29mg/(kg·d),连续7d。次日ipPTZ60mg/kg,观察动物行为变化,1d后处死动物,取左侧大脑固定用于原位杂交;取右侧海马组织用于半定量RT-PCR,检测海马CA₁、CA₃区神经元NMDRA1 mRNA的表达情况。结果原位杂交结果显示,阳性染色颗粒定位于海马神经元胞质内。石菖蒲和α-细辛醚治疗组海马区神经元阳性细胞数和平均吸光度均明显少于模型对照组(P<0.05)。半定量RT-PCR结果显示,石菖蒲和α-细辛醚治疗组海马组织中NMDAR1 mRNA的相对表达量均较显著低于模型对照组(P<0.05)。结论石菖蒲和α-细辛醚可能通过抑制海马区神经元谷氨酸NMDAR1表达而发挥抑制PTZ诱发的幼鼠癫痫发作。

Objective To explore the effect of Acorus gramimeus and its major components α-asarone on N-methyl-D-asperate recepter 1 (NMDAR1) mRNA levels of hippocamp neurons in epileptic animal models induced by pentylenetetrazol (PTZ). Methods PTZ 60 mg/kg was injected to the abdominal cavity of three weeks Wistar rats to prepare epileptic animal models. The animal models were randomly divided into three groups: epilepsy control, A. gramimeus and α-asarone as well as the normal control. Each group was administered through intraperitoneal injection. Both of two control groups were injected physiologic saline 1.0 mL/d, and the rest groups were injected A. gramimeus 2 350 mg/(kg·d) or α-asarone 29 mg/(kg·d) for 7 d, respectively. All rats were treated by PTZ 60 mg/kg through intraperitoneal injection next day. After their behaviors were observed for 24 h, animals were sacrificed. The expressions of NMDAR1 mRNA in hippocamp CA₁ and CA₃ of all rats were detected by in situ hybridization and semiquantitative RT-PCR. Results The results of in situ hybridization showed that positive staining granules were located in the cyptoplasm of hippocamp neurons. The number of positive cells and average absorbance of A. gramimeus group or α-asarone group was markedly less than that of epilepsy control (P<0.05). The semiquantitative RT-PCR results showed that NMDAR1 mRNA relative expression level of hippocamp neurons in A. gramimeus group or α-asarone group was lower remarkably than that in epilepsy control (P<0.05). Conclusion A. gramimeus and α-asarone inhibit epileptic seizure in immature rats induced by PTZ by decreasing the expression of glutamic acid receptor NMDAR1 in hippocamp neurons.

吉林省科技厅资助项目(20030430)；吉林省中药管理局资助项目(2004079)