CX3CL1-CX3CR1对颅内感染大鼠癎性发作敏感性及脑损伤的影响  

Effects of CX3CL1-CX3CR1 on the Sensitivity of Epileptic Seizures and Brain Injury in Rats with Intracranial Infection

作　　者：曹兴[1] 李志民[1] 蒲圣雄 余巨明[1] 蒋国会[1] CAO Xing;LI Zhi-min;PU Sheng-xiong;YU Ju-ming;JIANG Guo-hui(Department of Neurology,North Sichuan Medical College,Nanchong 637000,China)

机构地区：[1]川北医学院附属医院神经内科,南充市637000

出　　处：《中国临床神经科学》2020年第2期121-131,共11页Chinese Journal of Clinical Neurosciences

摘　　要：目的观察干预CX3CL1-CX3CR1对颅内感染模型大鼠癎性发作的敏感性及脑组织损伤的影响。方法脂多糖(LPS)诱导制作颅内感染模型大鼠,氯化锂(LiCl)-毛果芸香碱(Pilo)致癎LPS感染模型大鼠。①对LiCl-Pilo致癎敏感性及脑损伤的影响:随机分为4组,侧脑室注射LPS(LPS组)、侧脑室注射0.9%氯化钠(NaCl)溶液(对照组)、0.9%NaCl溶液致癎(NaCl+Pilo组)和LPS致癎(LPS+Pilo组)。用ELISA和Western blot分别检测各组海马组织IL-1β和TNF-α水平以及CX3CL1和CX3CR1水平;免疫组化方法检测神经元及小胶质细胞;采用行为学和电生理评估致癎大鼠的癫癎持续状态潜伏期及发作强度。②感染大鼠分别予以CX3CL1和CX3CR1处理,观察其对LiCl-Pilo诱导癫癎发作及脑组织的影响:随机分为NaCl+LPS组、CX3CL1+LPS组和抗CX3CR1抗体+LPS组,LiCl-Pilo诱导癫癎持续状态,采用行为学及电生理评估癫癎持续状态潜伏期及发作强度,免疫组化检测LPS对皮质区及海马CA1区的神经元和小胶质细胞的影响。结果①与对照组比较,LPS组海马CX3CL1、CX3CR1、IL-1β和TNF-α水平显著增加(均P<0.001),LiCl-Pilo致癎反应明显增强(P<0.001),神经元丢失明显(P<0.001);②与NaCl+LPS组比较,CX3CL1+LPS组大鼠的癎性发作敏感性无明显改变,但脑损伤加重(均P<0.001),抗CX3CR1抗体+LPS组的大鼠癎性发作敏感性降低,脑损伤较小。结论抗CX3CR1抗体可降低LPS感染模型大鼠对LiCl-Pilo致癎敏感性和发作程度,并可抑制小胶质细胞的激活和减少神经元的丢失。Aim To observe the effects of intervention CX3CL1-CX3CR1 on the seizure sensitivity and brain damage of rats with intracranial infection.Methods Intracranial infection model rats were induced by lipopolysaccharide(LPS),and then the epileptic seizures on LPS infection model rats was induced by lithium chloride(LiCl)-pilocarpine(Pilo).①The intracranial infection effects on LiCl-Piloinduced seizure sensitivity and brain injury were observed.Rats were randomly divided into 4 groups:a lateral ventricle injection LPS group(LPS group),a lateral ventricle injection 0.9% sodium chloride(NaCl)solution group(control group),a 0.9% NaCl solution induced epilepsy group(NaCl+Pilo group)and a LPS induced epilepsy group(LPS+Pilo group).The levels of IL-1β,TNF-α,CX3CL1,and CX3CR1 in the hippocampus of each group were detected by ELISA and Western blot.Immunohistochemistry was used to detect the effects of LPS on neurons and microglia in the cortical and hippocampal CA1 regions.Epileptic behavior and electrophysiology were used to analysis the seizure latent period and intensity.②The effects of CX3CL1 or CX3CR1 on the seizures and brain damage of LiCl-Pilo-induced and LPS infection model rats were observed.Rats were randomly divided into a NaCl+LPS group,a CX3CL1+LPS group and an anti-CX3CR1 antibody+LPS group,all the groups were induced epilepsy by LiCl-Pilo.Epileptic behavior and electrophysiology were used to analysis the seizure latent period and intensity.Immunohistochemistry was used to detect the effects of LPS on neurons and microglia in the cortical and hippocampal CA1 regions.Results①Compared with the control group,the levels of CX3CL1,CX3CR1,IL-1βand TNF-αin the hippocampus of the LPS group were significantly increased(all P<0.001),the epilepsy response of LiCl-Pilo was significantly enhanced(P<0.001),and the neuron loss was significant(P<0.001).②Compared with the NaCl+LPS group,the seizure sensitivity of the CX3CL1+LPS group was not significantly changed,but the brain damage was increased(all P<0.001),the se

关 键 词：癫癎持续状态 颅内感染 趋化因子 CX3CL1 CX3CR1 

分 类 号：R742.1[医药卫生—神经病学与精神病学]