摘要
目的探讨多黏菌素B(PMB)对全脑缺血再灌注模型大鼠脂多糖(LPS)所致损伤的保护作用及其机制。方法144只健康雄性SD大鼠均分为对照组(SH组)、模型组(IR组)、脂多糖组(LPS组)及多黏菌素B组(PMB+LPS组),后3组大鼠采用四血管阻断法建立大鼠全脑缺血再灌注模型,LPS组再灌注后即刻尾静脉注射脂多糖(500μg/kg),PMB+LPS组再灌注后即刻尾静脉注射LPS再注射PMB(0.5 mg/kg),SH组及IR组再灌注后即刻注射等量生理盐水;4组大鼠根据再灌注时间再均分为2、6、12、24、48及72 h六个亚组,比较各组大鼠不同时间点海马细胞凋亡率、LPS含量、神经行为学评分及Toll样受体4(TLR4)表达水平。结果不同再灌注时间点,SH组及IR组大鼠海马组织均检测到少量LPS,LPS组LPS含量于再灌注2 h时开始增多、24 h达高峰、72 h含量有所下降(P<0.05),PMB+LPS组各时间点海马LPS含量较LPS组减低(P<0.05);SH组大鼠海马细胞凋亡率在各时点均很低,IR组及LPS组大鼠海马细胞凋亡率于再灌注后2 h开始升高、24 h达峰值、72 h开始下降,LPS组>IR组>LPS+PMB组>SH组(P<0.05);与LPS组相比,其他3组大鼠神经行为学评分均升高,凋亡细胞数减少(P<0.05);与SH组比较,IR组各亚组海马CA1区椎体细胞受损严重,LPS组再灌注24 h时受损最严重,LPS+PMB组改变介于LPS组与IR组之间;SH组及IR组大鼠海马CA1区各时点TLR4表达较少,LPS组TLR4的表达于再灌注2 h时开始增多、24 h达高峰、随后开始下降(P<0.05),LPS+PMB组各时点与LPS组相比、TLR4表达均下降,差异有统计学意义(P<0.05)。结论全脑缺血再灌注模型大鼠脑组织内LPS含量随再灌注时间变化并造成大脑损伤,PMB对该种损伤有保护作用,其机制可能与抑制TLR4的表达有关。
Objective To explore the protective effect and the mechanism of Polymyxin B(PMB)during global cerebral ischemia-reperfusion injury in rats induced by endotoxin.Methods Healthy male SD rats(200-250 g in weight)were randomly divided into 4 groups according to the random number table:the sham group(SH Group),the cerebral ischemia-reperfusion group(IR Group),the LPS+I/R group(LPS Group)and the LPS+I/R+PMB group(LPS+PMB Group).Four vessels occlusion method was used to establish the model with global cerebral ischemia-reperfusion.LPS Group was injected into tail vein at the moment of reperfusion(500μg/kg).PMB 0.5 mg/kg and LPS 500μg/kg were injected into tail vein at the moment of reperfusion,PMB was injected after the LPS.The other two groups were given the same volume of normal saline.Rats were killed 2,6,12,24,48,and 72 h after reperfusion.The apoptosis rate,toxin levels,TLR4,and neurobehavioral scores at different time point were compared among the four goups.Results SH Group and IR Group showed the small amount of toxins.Toxin levels in LPS group was markedly increased 2 h after reperfusion,and LPS content reached the peak in 24 h,while declined in 72 h(P<0.05),Toxin levels in the hippocampus in the group of polymyxin B at all time points were significantly reduced compared with LPS group(P<0.05).SH Group had very low apoptosis rate at each time point,and apoptosis rate in IR Group and LPS Group began to increase 2 h after reperfusion,and reached the peak in 24 h,while it began to decline in 72 h.At each time point apoptosis showed LPS Group>LPS+PMB Group>IR Group>SH Group(P<0.05).The Neurobehavioral score of LPS Group was significantly reduced compared with the other three groups,and the number of apoptotic cells significantly increased(P<0.05).The pyramidal cells in CAl region of hippocampus in SH Group arrayed regularly with obvious boundary.In LPS Group the damage was more server at each time point(P<0.05).The change of LPS+PMB Group was just between IR Group and LPS Group.SH Group and the IR Group at each t
作者
郑思敏
李思远
牛晓丽
杨毅猛
薛荣亮
ZHENG Simin;LI Siyuan;NIU Xiaoli;YANG Yimeng;XUE Rongliang(Department of Anesthesiology,the Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710041,Shananxi,China)
出处
《贵州医科大学学报》
CAS
2021年第9期1011-1017,共7页
Journal of Guizhou Medical University
基金
国家自然科学基金项目(31300675)
陕西省卫生科研项目(2016D014)。
关键词
全脑缺血再灌注
脂多糖
细胞凋亡
多黏菌素B
TOLL样受体4
global brain ischemia and reperfusion
lipopolysaccharide(LPS)
apoptosis
polymyxin B(PMB)
toll like receptor 4(TLR4)
