半夏生物总碱对癫痫大鼠行为学、脑组织病理学及BDNF/Trk-B表达的影响

Effects of pinellia total alkaloids on neuroethology,brain histopathology and BDNF/Trk-B expression in epileptic rats

目的评价半夏生物总碱(PTA)对癫痫大鼠模型的神经保护作用。方法92只SPF级雄性SD大鼠在首次行为学测试(强迫路线转换测试、旷场活动及自发路线转换测试)后分为正常对照组及模型组。模型组经癫痫造模后再分为癫痫对照组、托吡酯组(0.06g/kg)、PTA低剂量组(0.4g/kg)和PTA高剂量组(0.8g/kg),与正常对照组同时灌胃14d后复查行为学测试。检测海马结构的组织形态改变、苔藓纤维发芽(MFS)现象及BDNF和Trk-B的蛋白表达量。结果与正常对照组比较,癫痫对照组的强迫路线转换行为比和自发路线转换行为比下降(各P<0.05),旷场活动进入格数升高(P<0.001);海马CA3区(P<0.01)、CA1区(P<0.01)及齿状回门区(P<0.05)的神经元数量下降,见苔藓纤维发芽现象(P<0.01);mBDNF和Trk-B表达下降而proBDNF表达上升(各P>0.05)。与癫痫对照组比较,半夏生物总碱提高自发路线转换行为比(0.4g/kg,P>0.05),提高CA3区(0.8g/kg,P<0.01)及齿状回门区(0.8g/kg,P<0.05)的神经元数量,降低苔藓纤维发芽程度(各P<0.05)及mBDNF(各P<0.01)的表达量。结论半夏生物总碱对癫痫大鼠存在神经保护作用,能显著降低海马结构神经元的减损、苔藓纤维发芽的程度及mBDNF的蛋白表达水平,并改善空间工作记忆障碍。

Objective To evaluate the neuroprotective effects of pinellia total alkaloids (PTA) on epileptic rats.Methods A total of ninety-two SPF male SD rats were divided into a normal control group and a model group after the first battery of behavioral tests,including the forced alternation test (FAT),the open field locomotion (OFL),and the spontaneous alternation test (SAT).The model group was administered pilocarpine to induce epilepsy and those that were successfully induced were divided once more into an epilepsy group,a topiramate group (0.06 g/kg),a PTA low-dose group (0.4 g/kg),and a PTA high-dose group (0.8 g/kg).A consecutive 14-day intragastrical treatment was administered to all the groups,followed by the second battery of behavioral tests.The tissue morphology changes of hippocampal formation,the mossy fiber sprouting (MFS) phenomenon and the protein expression of BDNF and Trk-B were detected.Results Compared with those of the normal control group,the ratios of the forced alternation behavior and the spontaneous alternation behavior of the epilepsy control group were decreased (both P<0.05),while the number of the OFL square entry was increased (P<0.001),and the number of neurons in hippocampal CA3 area (P<0.01),CA1 area (P<0.01) and the dentate hilus (DH) (P<0.05) decreased,and prominent MFS (P<0.01) was detected.The expression levels of mBDNF and Trk-B were decreased while the expression level of proBDNF was increased (all P>0.05).Compared with the epilepsy control group,PTA increased the spontaneous alternation behavior ratio (0.4 g/kg,P>0.05),increased the number of neurons in the CA3 area (0.8 g/kg,P<0.01) and DH (0.8 g/kg,P<0.05),lowered the severity of MFS (both P<0.05),and down-regulated the expression levels of mBDNF (both P<0.01).Conclusion PTA can exert neuroprotective effects on the epilepsy rat model by significantly reducing the severity of neuron loss,MFS and the protein expression level of mBDNF in the hippocampal formation and improving spatial working memory impairment.