氨甲环酸对脑出血大鼠NOX2/ROS/NLRP3通路及小胶质细胞活化的影响  

Effects of tranexamic acid on NOX2/ROS/NLRP3 pathway and microglia activation in rats with intracerebral hemorrhage

作　　者：李涛[1] 申哲[1] 冯阳 古选民[1] 方军超 LI Tao;SHEN Zhe;FENG Yang;GU Xuan-ming;FANG Jun-chao(Department of Neurosurgery,the First Affiliated Hospital of Henan University of Science and Technology,Luoyang,Henan 471000;Department of Surgical Intensive Care Unit,the First Affiliated Hospital of Henan University of Science and Technology,Luoyang,Henan 471000,China)

机构地区：[1]河南科技大学第一附属医院神经外科,河南洛阳471000 [2]河南科技大学第一附属医院外科重症监护室,河南洛阳471000

出　　处：《热带医学杂志》2021年第2期160-165,F0002,共7页Journal of Tropical Medicine

基　　金：河南省中医药科学研究专项课题应用研究(2019ZY1029)。

摘　　要：目的分析氨甲环酸对脑出血大鼠NADH氧化酶2(NOX2)/活性氧簇(ROS)/核苷酸结合寡聚化结构域样受体家族吡啉结构域蛋白3(NLRP3)通路及小胶质细胞活化的影响。方法采用随机数字表法将大鼠分为假手术组(15只)、模型组(13只)、氨甲环酸低剂量组(25 mg/mL,13只)、氨甲环酸中剂量组(50 mg/mL,14只)、氨甲环酸高剂量组(100 mg/mL,13只)。无菌胶原酶IV灌注法制备大鼠脑出血模型,造模成功后给药(6、24、48 h)后利用Garcia评分对大鼠神经功能进行评分;给药48 h后测定大鼠脑组织含水量及血肿体积。采用酶联免疫吸附(ELISA)法检测大鼠血清肿瘤坏死因子(TNF-α)、白介素-1β(IL-1β)的表达水平;免疫组织化学法检测大鼠小胶质细胞数目;蛋白印迹(WB)法检测大鼠脑组织蛋白NOX2、NLRP3、半胱氨酸蛋白酶(caspase-1)、IL-1β表达;活性氧检测试剂盒检测大鼠脑组织ROS含量。结果造模成功后,与假手术组(17.51±0.01)分比较,模型组(8.24±0.48)分、氨甲环酸(低、中、高剂量)组(8.27±0.46、8.15±0.54、8.19±0.52)分大鼠神经功能评分显著降低,差异有统计学意义(F=1290.268,P<0.05)。给药后,同一时间(6、24、48 h),与假手术组比较,模型组、氨甲环酸(低、中、高剂量)组大鼠神经功能评分显著降低,差异均有统计学意义(F=869.679、927.512、1105.559,P均<0.05);与模型组比较,氨甲环酸(低、中、高剂量)组大鼠神经功能评分显著升高,且呈剂量依赖性(P<0.05);与假手术组比较,模型组脑组织含水量、血肿体积、小胶质细胞数目、血清蛋白TNF-α、IL-1β表达水平、脑组织ROS含量、蛋白NOX2、NLRP3、caspase-1、IL-1β表达显著增加(P<0.05);与模型组比较,氨甲环酸(低、中、高剂量)组大鼠脑组织含水量、血肿体积、小胶质细胞数目、血清蛋白TNF-α、IL-1β表达水平、脑组织ROS含量、蛋白NOX2、NLRP3、caspase-1、IL-1β表达显著降低,且呈剂量依赖性(P<0.05)。�Objective To investigate the effects of tranexamic acid on nicotinamide adenine dinucleotide phosphate 2(NOX2)/reactive oxygen species(ROS)/NOD-like receptor family pyrin domain containing 3(NLRP3)pathway and microglia activation in rats with intracerebral hemorrhage.Methods The rats were randomly divided into sham operation group(15 rats),model group(13 rats),tranexamic acid low-dose group(25 mg/mL,13 rats),tranexamic acid medium dose group(50 mg/mL,14 rats),and high-dose tranexamic acid group(100 mg/mL,13 rats).The model of intracerebral hemorrhage was established by injecting sterile collagenase IV;the nerve function of rats was evaluated by Garcia score after administration(6,24,48 h);the water content of brain tissue and the volume of hematoma were measured 48 hours after administration.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression levels of tumor necrosis factor(TNF-α)and interleukin-1β(IL-1β)in serum.The number of microglia was detected by immunohistochemistry.The expression of NOX2,NLRP3,caspase-1 and IL-1βin brain tissue of rats was detected by Western blot.ROS content was detected by reactive oxygen species detection kit.Results After successful modeling,compared with that in the sham operation group(17.51±0.01),the neurological function scores in model group(8.24±0.48)and tranexamic acid(low,medium and high dose)groups(8.27±0.46,8.15±0.54,8.19±0.52)were significantly lower(F=1290.268,P<0.05);at the same time after administration,compared with that in the sham operation group,the neurological function scores in model group and tranexamic acid(low,medium and high dose)groups were significantly lower(F=869.679,927.512,1105.559,all P<0.05);compared with that in the model group,the neurological function scores of rats in tranexamic acid(low,medium and high dose)groups were significantly increased,in a dose-dependent manner(P<0.05);compared with those in the sham operation group,the water content of brain tissue,the volume of hematoma,the number of microglia,the expressio

关 键 词：氨甲环酸 脑出血 NADH氧化酶2 核苷酸结合寡聚化结构域样受体家族吡啉结构域蛋白3 小胶质细胞 

分 类 号：R743.34[医药卫生—神经病学与精神病学]