右美托咪定对大鼠骨折模型所致的焦虑情绪及海马内神经炎症的调节作用  

Effects of dexmedetomidine on anxiety and neuroinflammation in the hippocampus induced by fractures in rats

作　　者：朱建宝 陈安琪 刘宏亮 ZHU Jianbao;CHEN Anqi;LIU Hongliang(Department of Anesthesiology,Haimen District People's Hospital,Nantong 226100,China)

机构地区：[1]南通市海门区人民医院麻醉科,南通226100

出　　处：《空军航空医学》2024年第2期122-127,共6页AVIATION MEDICINE OF AIR FORCE

基　　金：江苏省优势学科建设工程项目(YSHL0803-918)。

摘　　要：目的通过建立大鼠骨折模型研究右美托咪定(dexmedetomidine,DEX)对大鼠骨折导致的焦虑情绪及海马内神经炎症的调节作用。方法采用自由饮水模式将40只成年雄性Wistar大鼠随机分为对照组(空白对照组)、DEX组、手术组(对大鼠进行右股骨截骨术)、手术+DEX组(骨折后的大鼠腹膜内注射12μg/kg DEX),在模型建立成功后6 h、24 h、7 d通过惊吓反应测试大鼠的焦虑情绪,酶联免疫吸附实验检测大鼠血清及海马组织中炎症因子[肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-1β、IL-6]的表达,TUNEL染色定量海马组织中的凋亡细胞,蛋白质印迹检测海马组织中TNF-α、IL-1β、IL-6、神经型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)、NADPH氧化酶2抗体(NADPH oxidase2,NOX2)、4-羟基壬烯醛(4-Hydroxynonenal,4-HNE)、Bcl-2关联X蛋白(Bcl-2 associated X protein,Bax)和B淋巴细胞瘤-2(B-cell lymphoma-2,Bcl-2)的蛋白表达。结果与对照组相比,手术组血清TNF-α、IL-1β和IL-6和海马组织中TNF-α、IL-1β和IL-6 mRNA水平升高(P均<0.001),海马组织中神经元细胞凋亡数量增加,Bcl-2(P<0.001)和nNOS(P=0.001)表达水平降低,Bax(P<0.001)、4-HNE(P=0.001)、NOX2(P=0.003)、ROS水平(P=0.009)增加;与手术组相比,手术+DEX组血清TNF-α、IL-1β和IL-6和海马组织中TNF-α、IL-1β和IL-6 mRNA水平降低(P均<0.001),海马组织中神经元细胞凋亡细胞数量、Bax蛋白水平(P=0.008)、4-HNE(P<0.001)、NOX2(P<0.001)、ROS(P=0.008)水平降低,神经元细胞中Bcl-2(P=0.005)、nNOS(P<0.001)水平升高。结论右美托咪定可明显改善骨折大鼠的焦虑状态,减轻神经炎症和神经元凋亡。Objective To establish a rat fracture model to study the regulatory effects of dexmedetomidine on anxiety and hippocampal neuroinflammation caused by fractures in rats.Methods Forty adult male Wistar rats were randomly divided into four groups in a free drinking water mode:the control group(blank control group),DEX group(dexmedetomidine group),surgery group(right femur osteotomy),and surgery+DEX group(intraperitoneally injected with 12μg/kg DEX after fracture).At 6 h,24 h and 7 d after the establishment of the model,the anxiety of the rats was measured via fright response,the expressions of inflammatory factors(TNF-α,IL-1β,IL-6)in the serum and hippocampal tissue of the rats were detected by ELISA,and the apoptotic cells in the hippocampus were quantified by TUNEL staining.Western blot was used to detect the expressions of TNF-α,IL-1β,IL-6,nNOS,NOX2,4-HNE,Bax and Bcl-2 proteins in the hippocampus.Results Compared with the control group,the serum levels of TNF-α,IL-1βand IL-6 and the mRNA levels of TNF-α,IL-1βand IL-6 in the hippocampus of the operation group were increased(P<0.001),and the number of apoptotic cells was increased.The expression levels of Bcl-2(P<0.001)and nNOS(P=0.001)in hippocampus were decreased,while the expression levels of Bax(P<0.001)and 4-HNE(P=0.001),NOX2(P=0.003)and ROS(P=0.009)in hippocampus were increased.The serum levels of TNF-α,IL-1βand IL-6 and the mRNA levels of TNF-α,IL-1βand IL-6 in hippocampal tissue were decreased in the operation+DEX group(P<0.001),the number of apoptotic cells and the level of Bax protein were significantly decreased(P=0.008).The levels of 4-HNE(P<0.001),NOX2(P<0.001)and ROS(P=0.008)in hippocampus were decreased,while the expression levels of Bcl-2(P=0.005)in neurons and nNOS(P<0.001)in hippocampus were increased.Conclusion Dexmedetomidine can significantly improve the anxiety state,reduce neuroinflammation and neuronal apoptosis in rats with fractures.

关 键 词：右美托咪定 骨折 焦虑情绪 神经炎症 

分 类 号：R4[医药卫生—临床医学]