补阳还五汤通过抑制炎症反应对创伤性癫痫小鼠的预防作用

目的：探讨补阳还五汤对创伤性癫痫小鼠模型的预防作用及可能的作用机制。方法：将30只C57BL/6小鼠按照随机数字表法分为假手术组、模型组、补阳还五汤组，每组10只。对模型组、补阳还五汤组小鼠施行皮质切割手术，假手术组只进行颅骨钻孔。术后第2天，假手术组、模型组给予10 mL/kg生理盐水（灌胃治疗），补阳还五汤组给予补阳还五汤（32 g/kg）（灌胃治疗），连续干预10 d。第21天腹腔注射戊四氮（PTZ），比较各组小鼠癫痫首次大发作PTZ剂量、首次大发作潜伏期、发作等级、小发作总次数、大发作持续时间、体质量、大脑皮质组织病理形态改变及大脑皮质组织白细胞介素6（IL-6）、白细胞介素1β（IL-1β）、肿瘤坏死因子α（TNF-α）蛋白表达。结果：与假手术组比较，模型组小鼠癫痫首次大发作PTZ剂量少，潜伏期短，持续时间长，发作次数多，大脑皮质神经元细胞少，尼氏小体破损严重，大脑皮质组织IL-6、IL-1β、TNF-α蛋白表达高，差异均有统计学意义（均P<0.05）；与模型组比较，补阳还五汤组小鼠癫痫首次大发作PTZ剂量多，潜伏期长，发作持续时间短，发作次数少，大脑皮质神经元细胞多，排列相对紧密，尼氏小体破损轻，大脑皮质组织IL-6、IL-1β、TNF-α蛋白表达低，差异均有统计学意义（均P<0.05）。模型组小鼠癫痫发作等级较假手术组高，但差异无统计学意义（P>0.05）；补阳还五汤组小鼠癫痫发作等级较模型组低，但差异无统计学意义（P>0.05）。结论：补阳还五汤可提高创伤性癫痫小鼠癫痫诱发阈值，改善大脑皮质组织病理变化，促进大脑皮质神经元细胞修复和再生；其作用机制可能与减轻大脑皮质炎症反应有关。

Buyang Huanwu Decoction Prevents Posttraumatic Epilepsy by Inhibiting Inflammatory Response in Mice

To investigate the preventive effects and underlying mechanisms of Buyang Huanwu Decoction on a mouse model of posttraumatic epilepsy.Methods:Thirty C57BL/6 mice were randomly divided into three groups according to a random number table：sham operation group,model group,and Buyang Huanwu Decoction group,with 10 mice in each group.The mice in the model and Buyang Huanwu Decoction groups underwent cortical cutting surgery,while those in the sham operation group only had cranial drilling.Starting on the second day post-surgery,the sham operation and model groups received saline(oral gavage) daily at 10 mL/kg,while the Buyang Huanwu Decoction group received oral Buyang Huanwu Decoction(32 g/kg) daily for 10 days.On the 21st day,pentylenetetrazol(PTZ) was injected intraperitoneally.Various parameters were compared,including the PTZ dose for the first generalized seizure,latency to the first seizure,seizure grade,total number of minor seizures,duration of major seizures,body weight,histopathological changes in cortical tissue,and protein expression of interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α) in cortical tissues.Results:Compared with the sham operation group,the model group had a lower PTZ dose for the first seizure,shorter latency,longer seizure duration,more seizures,fewer cortical neurons,severe Nissl body damage,and higher protein expression of IL-6,IL-1β,and TNF-α in the cortical tissues(all P<0.05).Compared with the model group,the Buyang Huanwu Decoction group had a higher PTZ dose for the first seizure,longer latency,shorter seizure duration,fewer seizures,more cortical neurons with relatively tight arrangement,less Nissl body damage,and lower protein expression of IL-6,IL-1β,and TNF-α in the cortical tissues(all P<0.05).Although the seizure grade in the model group was higher than that in the sham operation group,the difference was not statistically significant(P>0.05).The seizure grade in the Buyang Huanwu Decoction group was lower than that in the model group,but the difference was not statistically significant(P>0.05).Conclusion:Buyang Huanwu Decoction can increase the seizure threshold in posttraumatic epilepsy mice,improve histopathological changes in cortical tissues,and promote repair and regeneration of cortical neurons.Its mechanism of action may be related to the reduction of inflammatory responses in the cortical tissues.