亮蓝G减轻急性CO中毒大鼠海马的损伤  

Brilliant blue G attenuates hippocampal injury of rats with acute carbon monoxide poisoning

作　　者：杨坤丽 沈慧[2] 李璐[3] 张利彬[3] 李秀娟[3] 魏林郁[3] 黄亚迪 赵红岗[3] 江林华 李东亮 YANG Kun-li;SHEN Hui;LI Lu;ZHANG Li-bin;LI Xiu-juan;WEI Lin-yu;HUANG Ya-di;ZHAO Hong-gang;JIANG Lin-hua;LI Dong-liang(Department of Physiology, Sanquan Medical College, Xinxiang Medical University, Xinxiang 453003, Chain;Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang 453003, Chain;The Third Affiliated Hospital, Xinxiang Medical University, Xinxiang 453003, Chain)

机构地区：[1]新乡医学院三全学院生理学教研室,河南新乡453003 [2]新乡医学院第三附属医院,河南新乡453003 [3]新乡医学院生理与神经生物学教研室,河南新乡453003

出　　处：《中国病理生理杂志》2018年第12期2202-2208,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81371346; No.81271376);河南省高校科技创新团队支持计划(No.161RTSTHN020);河南省教育厅科学技术研究重点项目(No.16A310011; No.16A310013)

摘　　要：目的:观察亮蓝G(BBG)对急性一氧化碳中毒(ACMP)引起的大鼠海马组织损伤的影响,探讨配体门控离子通道嘌呤能P2X_7受体(P2X_7R)在一氧化碳中毒脑损伤中的作用。方法:80只8～10周龄SD大鼠分为对照(control)组、ACMP组、ACMP+BBG组和BBG组。采用腹腔注射CO(100 m L/kg)的方法制备大鼠ACMP模型。检测静脉血中的碳氧血红蛋白(Hb CO)浓度来判断CO中毒程度。RT-qPCR检测大鼠海马组织P2X_7R的mRNA表达。干湿称重法检测海马组织水肿程度。ELISA法检测海马组织促炎因子白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)和IL-6的含量。Morris水迷宫实验评价学习记忆能力。HE染色观察海马CA1区细胞形态学改变。结果:与control组(100%)相比,染毒6 h后ACMP组大鼠的存活率降低至55%;海马组织P2X_7R的mRNA表达及促炎因子IL-1β、TNF-α和IL-6的含量均明显增加(P <0. 05);含水量升高到80. 72%±0. 93%;大鼠逃避潜伏期明显延长,在目标象限探索时间明显缩短。值得注意的是,BBG预处理可以明显改善ACMP诱导的这些海马损伤。另外,大鼠染毒后3 d,海马CA1区的神经元排列紊乱稀疏,细胞形态不完整,细胞核深染、固缩。而BBG预处理能够显著改善CA1区的细胞形态。结论:P2X_7R与ACMP诱导的海马损伤相关。BBG能够增加ACMP大鼠的存活率,减少促炎因子的释放,减轻海马水肿,改善学习记忆能力,减轻ACMP引起的CA1区神经元损伤。AIM:To explore the role of ligand-gated ion channel purinergic P2X7receptor(P2X7R)in acute carbon monoxide poisoning(ACMP)-induced brain injury,and to observe the effects of brilliant blue G(BBG)on ACMP-induced hippocampal injury of rats.METHODS:Male Sprague-Dawley rats(n=80)were divided into4groups including control group,ACMP group,ACMP+BBG group and BBG group.ACMP model was established by intraperitoneal injection of CO at100mL/kg.The degree of CO poisoning was determined by measuring the concentration of carboxyhemoglobin(HbCO)in venous blood.RT-qPCR was utilized to determine the mRNA level of P2X7R.Wet-dry weight ratio was calculated to evaluate the edema in the hippocampus.ELISA was used to examine the concentrations of pro-inflammatory factors including interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)and IL-6.Morris water maze test was used to evaluate the learning and memory abilities.The morphological changes of the neurons located in hippocampal CA1region were observed by HE staining.RESULTS:The rat survival rate in ACMP group(55%)was significantly reduced compared with control group(100%),while the mRNA expression of P2X7R and the levels of pro-inflammatory factors including IL-1β,TNF-αand IL-6in ACMP group were significantly increased(P<0.05).Moreover,ACMP administration increased the water content of hippocampal tissues and the escape latency of the rats,while decreased the exploration time in the target quadrant.All the effects induced by ACMP were reversed by BBG treatment.Additionally,ACMP treatment for3d resulted in cell disarrangement and morphologyical defect,and the nucleus was deeply dyed and condensed.However,BBG obviously alleviated the toxic effects of ACMP.CONCLUSION:P2X7R is involved in ACMP-induced neuronal damage in hippocampus.BBG increases the survival rate,reduces the release of pro-inflammatory cytokines and the edema in the hippocampus,improves the learning and memory abilities,and attenuates neuronal damage in the CA1region under ACMP.

关 键 词：嘌呤能P2X7受体 急性一氧化碳中毒 亮蓝G 海马 促炎因子 

分 类 号：R595.1[医药卫生—内科学] R363[医药卫生—临床医学]