摘要
目的探究迷迭香酸对NLRP3炎性小体活化的影响,从而进一步探究其对创伤性颅脑损伤大鼠脑组织损伤和海马神经元凋亡的影响。方法采用控制性皮层撞击损伤(CCI)模型法建立大鼠创伤性颅脑损伤模型,将小鼠随机分成5组,加药组分别腹腔注射5、10、20 mg/kg迷迭香酸,然后评估大鼠的神经功能缺陷评分;计算各组大鼠脑含水率及脑指数;苏木精-伊红染色观察各组大鼠脑组织海马区神经元病理学变化;TUNEL检测神经元凋亡情况;尼氏小体染色观察神经元损伤情况;蛋白印迹法检测各组大鼠脑前额叶脑源性神经营养因子(brain derived neurotrophic factor,BDNF)、神经生长因子(nerve growth factor,NGF)、NLRP3、凋亡相关微粒蛋白(apoptosis-associated speck-like protein containing CARD,ASC)、Caspase-3的蛋白表达水平;试剂盒检测活性氧(reactive oxygen species,ROS),超氧化物岐化酶(superoxide dismutase,SOD),乳酸脱氢酶(lactate dehydrogenase,LDH)的含量。结果与健康对照组比较,脑损伤模型组神经功能缺陷评分、脑含水率以及脑指数均显著升高(P<0.05),神经元凋亡率,BDNF、NGF、NLRP3、ASC、Cleaved Caspase-3蛋白表达水平,ROS和LDH的含量均显著升高(P<0.05),SOD活性显著降低(P<0.05)。与脑损伤模型组比较,迷迭香酸中、高剂量组神经功能缺陷评分、脑含水率以及脑指数均显著降低(P<0.05),海马区神经元病变范围及程度减轻,海马区神经元损伤程度减轻。与脑损伤模型组比较,迷迭香酸中、高剂量组神经元凋亡率,BDNF、NGF、NLRP3、ASC、Cleaved Caspase-3蛋白表达水平,ROS和LDH的含量均显著降低(P<0.05);SOD含量显著升高(P<0.05)。结论迷迭香酸可抑制NLRP3炎性小体的活化和海马区神经元凋亡并减轻创伤性颅脑损伤大鼠脑组织损伤。
This study was performed to investigate the effect of rosmarinic acid on the activation of NLRP3 inflammatory bodies,and further explore its effect on brain tissue damage and hippocampal neuron apoptosis in traumatic brain injury rats.The rat model of traumatic craniocerebral injury was established using the controlled cortical impact injury model(CCI)method.Mice were randomly divided into 5 groups,and the medicated group was intraperitoneally injected with 5,10,20 mg/kg of rosmarinic acid,and then neurological deficit scores was evaluated in rats,and Brain water content and brain index were calculated in each group.Hematoxylin-eosin staining was used to observe the pathological changes of neurons in the hippocampus of each group of rats;TUNEL was used to detect neuronal apoptosis;Nissl body staining was used toobserve the damage of neurons.Western blot was usedto detect the protein expression levels of BDNF,NGF,NLRP3,ASC,and Caspase-3 in the prefrontal lobe ofeach group,while corresponding kits were used to detect the content of SOD,ROS,LDH.Data showed that as compared with healthy control group,the brain injurygroup demonstrated increases in neurological dysfunction score,brain moisture content,brain index,neuronalapoptosis rate,the expression level of BDNF,NGF,NLRP3,ASC and Cleaved Caspase-3 protein,and the content ofROS and LDH(P<0.05),while a decrease in SOD activity(P<0.05).The scores of neurological deficits,brainmoisture content and brain index in the medium and high dose groups of rosmarinic acid were significantlydecreased compared with the brain injury model group(P<0.05),furthermore,the range and degree of hippocampalneuronal lesion and the degree of hippocampal neuronal injury were reduced.The apoptosis rate of neurons,expression levels of BDNF,NGF,NLRP3,ASC,Cleaved Caspase-3,ROS and LDH in the medium and high dosegroups were significantly decreased compared with the brain injury model group(P<0.05),while SOD content wassignificantly increased(P<0.05).In conclusion,rosmarinic acid can inhibit the act
作者
罗飞
张明辉
陈立珂
陈岷辉
丁昊
毛伯镛
LUO Fei;ZHANG Minghui;CHEN like;CHEN Minhui;DING Hao;MAO Boyong(Department of Neurosurgery,Zigong Fourth People’s Hospital,Zigong 643000,China;Department of Neurosurgery,First Affiliated Hospital of West China Hospital,Sichuan University,Chengdu 610041,China)
出处
《免疫学杂志》
CAS
CSCD
北大核心
2021年第7期568-574,共7页
Immunological Journal
基金
四川省卫生计生委科研课题(140110)。
