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瑞马唑仑对大鼠脑缺血再灌注后神经认知功能的影响

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目的 研究瑞马唑仑对大鼠脑缺血再灌注后记忆缺陷、神经元损伤及神经营养因子产生的影响.方法 取36只清洁健康SD雄性大鼠,建立脑缺血再灌注损伤模型.将大鼠分为MACO模型组(0.9%生理盐水,10 mg/kg)、MCAO+瑞马唑仑组(瑞马唑仑,10 mg/kg),MCAO+MCC950组(MCC950,10 mg/kg),各组大鼠于再灌注前尾静脉注射相应药物.另取12只未建模大鼠为假手术组(0.9%生理盐水,10 mg/kg,尾静脉注射).采用神经功能评分和水迷宫实验测定大鼠神经功能.取脑组织,用TTC染色和HE染色,测定脑梗死面积和神经细胞损伤情况;用qRT-PCR和 Western blot测定脑BDNF、NGF表达;取血清,用ELISA法测定血清MDA和LDH含量.结果 与MACO组比较,MCAO+瑞马唑仑组、MCAO+MCC950组神经功能评分和脑梗死面积均减小,血清MDA和LDH含量均降低,脑组织NGF蛋白表达水平增大(P<0.05),神经元细胞排列较整齐,神经元细胞数目增多,胞周空泡减少,血管周围间隙减少.与假手术组比较,MCAO+瑞马唑仑组、MCAO+MCC950组脑中BDNF、NGF基因的表达水平增大(P<0.05).结论 瑞马唑仑能够增加神经营养因子的产生,抑制NLRP3介导的炎症反应,具有减弱神经功能损伤,减轻脑缺血再灌注损伤的作用,适用于围术期脑保护.
Effect of Remazolam on neurocognitive function after cerebral ischemia reperfusion in rats
Objective To investigate the effects of Remazolam on memory deficits,neuronal injuryand neu-rotrophic factor production after cerebral ischemia-reperfusion in rats.Methods 36 clean and healthy SD male rats were selected to establish a model of cerebral ischemia-reperfusion injury.The rats were divided into the MACO model group(0.9%normal saline,10 mg/kg),MCAO+Remazolam group(Remazolam,10 mg/kg)and MCAO+MCC950 group(MCC950,10 mg/kg).The corresponding drugs were injected into the tail vein of each group of therats before reperfusion.Another 12 unmodeled rats were selected as sham surgery group(0.9%normal saline,10 mg/kg,tail vein injection).Neurological function scores and water maze experiments were used to measure the neural function of the rats.The cerebral infarct size and nerve cell injury were measured by TTC and HE.The expressions of brain-derived neurotrophic factor(BDNF)and nerve growth factor(NGF)were measured by qRT PCR and Western blot.The contents of MDA and LDH in serum were determined by ELISA.Results Compared with MACO group,MCAO+Remazolam group and MCAO+MCC950 group showed a decrease in neurological function score and stroke area,as well as a decrease in serum MDA and LDH levels.The expression level of NGF protein in brain tissuewas increased(P<0.05),and the arrangement of neuronal cells was more orderly,with an increase in the number of neuronal cells,a decrease in pericellular vacuoles,and a decrease in perivascular spaces.Compared with sham surgery group,the expression levels of BDNF and NGF genes in the brain of MCAO+Remazolam group and MCAO+MCC950 group were increased(P<0.05).Conclusion Remazolam can increase the production of neurotrophic factors,inhibit NOD-1ike receptor pyrindomaincontaining three NLRP3 mediated inflammatory response,weaken neurological injury,and alleviate cerebral ischemia-reperfusion injury,to make it suitable for perioperative brain protection.

Remazolamcerebral ischaemia/reperfusionNLRP3 inflammasomebrain-derived neurotro-phic factor(BDNF)nerve growth factor(NGF)

耿强、文进秋、张冰、郑敏

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新疆医科大学附属肿瘤医院麻醉与围术期医学中心,乌鲁木齐 830011

瑞马唑仑 脑缺血再灌注 NLRP3炎症小体 脑源性神经营养因子 血清神经生长因子

新疆维吾尔自治区自然科学基金

2022D01C790

2024

新疆医科大学学报
新疆医科大学

新疆医科大学学报

CSTPCD
影响因子:0.76
ISSN:1009-5551
年,卷(期):2024.47(5)