长托宁对热性惊厥幼鼠海马神经元的保护作用

摘要

目的：探讨长托宁（盐酸戊乙奎醚注射液）干预对热性惊厥（FS ）幼鼠海马神经元损伤的保护作用及其可能机制。方法54只14日龄新生SD幼鼠随机分为3组，即盐水对照组、FS模型组、长托宁干预组，根据处死时间再分为12 h、24 h及48 h亚组。采用低剂量海人藻酸与脂多糖腹腔内注射建立幼鼠FS模型，长托宁干预组在建模同时给予长托宁0．45 mg/kg ，观察比较各组幼鼠惊厥表现，采用苏木精-伊红（H-E）染色法观察记录各组幼鼠海马CA1区神经元结构变化，应用原位末端标记法（TUNEL）观察并记录各组海马神经细胞凋亡数。结果L PS联合低剂量K A诱导FS模型组与长托宁干预组幼鼠惊厥发作，建立FS幼鼠模型。FS模型组、长托宁干预组幼鼠惊厥潜伏期差别无显著性，惊厥持续时间分别为（27．74±6．92）min和（21．74±6．60）min ，惊厥程度评分（级）分别为（3．80±0．94）min和（3．18±0．92）min ，差别均有统计学意义（P均＜0．05）。与FS模型组比较，长托宁干预组各时间点海马CA1区神经元变性及丢失程度减轻。与 FS模型组比较，长托宁干预组各时间点海马CA1区TUNEL阳性细胞数均明显减少（P＜0．05）。结论长托宁通过减少海马部位神经元细胞凋亡对 FS幼鼠海马神经元有保护作用。%Objective The main purpose of the present study was to find out whether the penehy-clidine hydrochloride (PHC) has the neuroprotective effect on seizure-induced hippocampal neuron dam-age . Methods Sixty-four cases of 14-day-old Sprague-Dawley rats were divided into three groups ran-domly :the normal saline control group ,the hyperthermic seizure group ,and the PHC treated group . In-traperitoneal injection of LPS combined with KA was used to establish rat model with FS . The rats were injected intraperitoneally with PHC at each time (15 minutes before modeled ,every 12 hour after mod-eled) . Then onset latency ,duration and grade of FS in different groups were observed and compared . Then the histopathology changes in hippocampus were viewed by HE staining and electron-microscope ,the neuron apoptosis was detected by TdT-mediated dUTP nick end labeling (TUNEL) . Results LPS com-bined with KA of intraperitoneal injection can induce febrile seizure . In PHC treated group ,the rats FS duration and FS grade were significantly lower than those in FS control group (P<0 .05) ,although no sig-nificant gap was observed on FS onset latency between them . In FS control group ,HE-staining pattern of hippocampal CA1 region showed lots of disordered neurons with confused polarity and vacuoles formed . While in PHC treated groups ,the arrangement of neurons were regular ,only a small number of neurons had changed . In FS group ,at the 24 h point after seizure ,TUNEL-positive cell in hippocampus CA1 re-gion increased most significantly comparing with PHC treated group (P<0 .05) . Conclusion The pene-hyclidine hydrochloride can lighten the febrile seizure-induced hippocampal neuron damage in rats by inhib-iting cell apoptosis .