摘要
目的探讨RNA聚合酶Ⅲ负调控因子(RNA polymeraseⅢnegative regulator,MAF1)在脓毒症相关性脑病(Sepsis-associated encephalopathy,SAE)大鼠模型中的作用及其对核苷酸结合寡聚化结构域(Nucleotide-binding oligomerization domain,NOD)样受体热蛋白结构域相关蛋白3(NOD-like receptor thermoprotein structural domain-associated protein 3,NLRP3)炎症小体的影响。方法100只大鼠分为假手术(Sham)组(10只)、SAE组(30只)、SAE+阴性对照(Negative control,NC)组(30只)、SAE+MAF1组(30只),采用盲肠结扎穿孔模型(Cecal ligation and puncture,CLP)诱发大鼠脓毒症,术后3 h分别通过左颈内动脉注射生理盐水、生理盐水、对照质粒、MAF过表达质粒各200μL,监测术后24 h内存活大鼠SAE发病情况;采用水迷宫试验观察认知功能;苏木精-伊红(Hematoxylin eosin,HE)及原位末端转移酶标记(Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling,TUNEL)染色观察病理变化及海马神经元凋亡情况;检测海马组织中白细胞介素(Interleukin,IL)-1β,IL-18水平及MAF1,NLRP3、凋亡相关斑点样蛋白(Apoptosis associated speck like protein containing,ASC)、半胱氨酸天冬氨酸蛋白酶-1(Cystein-asparate protease-1,Caspase-1)表达水平。结果术后24 h内SAE组、SAE+NC组、SAE+MAF1组SAE发病率分别为64.00、60.00、40.00%(P>0.05)。与Sham组比较,SAE组、SAE+NC组大鼠水迷宫试验目标象限停留时间缩短,穿越平台次数减少(P<0.05);与SAE+NC组比较,SAE+MAF1组大鼠目标象限停留时间延长,穿越平台次数增多(P<0.05)。HE染色显示,Sham组海马组织结构完整;SAE组和SAE+NC组海马CA1区组织结构完整性破坏,细胞排列紊乱,大量炎性细胞浸润及神经元肿胀、坏死、脱失;SAE+MAF1组上述病理改变减轻,但仍存在细胞排列紊乱、炎性细胞浸润等情况。Sham组、SAE组、SAE+NC组、SAE+MAF1组海马神经元凋亡率分别为(3.20±1.02)、(56.00±8.14)、(54.60±8.54)、(31.40±6.06)%;SAE组
Objective To investigate the effect of RNA polymeraseⅢnegative regulator(MAF1)on the inflammatory body of nucleotide-binding oligomerization domain(NOD)receptor heat protein domain associated Protein 3(NLRP3)in a rat model of sepsis associated encephalopathy(SAE).Methods One hundred SD rats were divided into Sham group(n=10),SAE group(n=30),SAE+negative control(NC)group(n=30)and SAE+MAF1 group(n=30).The cecal ligation and perforation(CLP)model was used to induce sepsis in rats.Three hours after operation,200μL each of normal saline,control plasmid,and MAF overexpression plasmid were injected through the left internal carotid artery.SAE incidence in rats was monitored within 24 hours after operation.Cognitive function was evaluated by water maze test,pathological changes and apoptosis of hippocampal neurons were determined by hematoxylin eosin(HE)and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling(TUNEL)staining.The levels of interleukin(IL-1β)and IL-18,and the expression levels of MAF1,NLRP3,apoptotic speckle like protein(ASC)and caspase-1 in the hippocampus were examined.Results The incidence of SAE within 24 hours after surgery was 64.00%,60.00%and 40.00%in the SAE group,SAE+NC group and SAE+MAF1 group respectively,with no statistical difference between the three groups(P>0.05).Compared with the Sham group,the rats in the SAE and SAE+NC groups had a shorter residence time in the target quadrant and a reduced number of platform crossings in the water maze test(P<0.05).Compared with the SAE+NC group,rats in the SAE+MAF1 group had longer dwell time in the target quadrant and more times of crossing the platform(P<0.05).HE staining showed that the hippocampal in the Sham group was structurally intact.In the SAE and SAE+NC groups,the structural integrity of the hippocampal CA1 region was destroyed,with disorganized cell arrangement,massive inflammatory cell infiltration and neuronal swelling,necrosis and loss of neurons.The above pathological changes were reduced in the SAE+MAF1 group
作者
孟文勤
郝颖楠
王蓉
付璇
李彩霞
Meng Wenqin;Hao Yingnan;Wang Rong(ICU of People's Hospital of Inner Mongolia Autonomous Region,Hohhot Inner Mongolia 010010)
出处
《卒中与神经疾病》
2023年第4期361-366,共6页
Stroke and Nervous Diseases
