肝硬化门静脉高压对大鼠认知功能和N-甲基-D-天门冬氨酸受体2B亚基表达的影响  

Influences of cirrhotic portal hypertension on rats＂ cognitive function and N-methyl-D-aspartic acid receptor 2B expression level

作　　者：谢伟斌[1] 苏工[1] 夏瑜秦[1] 蒋轶岭[1] 刘卫东[1] 

机构地区：[1]常州市第三人民医院麻醉科,213001

出　　处：《国际麻醉学与复苏杂志》2016年第12期1072-1076,共5页International Journal of Anesthesiology and Resuscitation

基　　金：常州市科技局社会发展计划项目（CJ20122009）

摘　　要：目的研究肝硬化门静脉高压对大鼠认知功能及N-甲基-D-天门冬氨酸受体（N-methyl-D-aspartic acid receptor，NR）2B亚基（NR2B）表达的影响。方法雄性SD大鼠37只，按照完全随机法分为两组：肝硬化组（25只），采用四氯化碳．花生油溶液方法制造肝硬化门静脉高压大鼠模型；对照组（12只）。两组于造模前及造模成功后第1、3、5、7天分别利用跳台法和Y-迷官法对各大鼠进行行为学测试；测试完成后处死大鼠，取海马组织，RT-PCR方法检测大鼠海马NR2B mRNA的水平，Western blot检测海马NR2B蛋白表达水平，免疫组化法检测大鼠海马CA1区NR2B蛋白分布的变化。ELISA法检测肝损伤相关指标ALT、AST、超氧化物歧化酶（superoxide dismutase，SOD）、丙二醛（malondialdehvde，MDA）、TNF-α、IL-1、IL-6的含量。结果肝硬化组AST、ALT、TNF-α、IL-1、IL-6、MDA分别为（261±7）、（178±7）U／L、（206±18）、（0．46±0．11）、（298±41）μg，L、（19．7±2．5）μmol／L，较对照组明显升高（P〈0．01），SOD为（96±7）U／ml，较对照组明显降低（P〈0．01）。与对照组比较：肝硬化组跳台潜伏时间延长、Y-迷宫、错误次数增加（P〈0．01），海马中NR2B mRNA的水平及NR2B的蛋白表达明显降低（P〈0．01），海马CA1区NR2B免疫组化表达明显下降（P〈0．01）。结论肝硬化门静脉高压引起大鼠认知功能的降低，同时下调海马中NR2B mRNA和蛋白的表达及CA1区锥形细胞中NR2B的表达。Objective Research on the influences of cirrhotic portal hypertension on rats＇ hcongnitive function and N- methyl-D-aspartic acid receptor 2B （NR2B） expression level. Methods Thirty seven male SD rats were randomly divided into 2 groups. In the cirrhotic portal hypertension group （group A）, 25 rats were inducted into portal hypertension rat model using carbon tetrachloride-peanut oil solution. The remaining 12 rats served as control group （group B）. Step-down method and Y-maze method were used in both groups prior to modeling and 1, 3, 5, 7 d after modeling respectively to study their behavior. All rats were killed after testing and hippocampi were collected. RT-PCR was used to detect NR2B mRNA level in the hippocampi, and Western blot was used to detect NR2B protein expression level. Immuno-histochemical method was used to detect NR2B protein distribution changes. ELISA was used to detect the level of ALT and AST, superoxide dismutase （SOD）, malondialdehyde （MDA）, TNF-α, IL-1 and IL-6. Results The level of AST, ALT, TNF-α, IL-1, IL-6 and MDA in group A were （261±7）, （178±7） U/L, （206±18）, （0.46±0.11）, （298±41） μg/L, （19.7±2.5） μmol/L, which were much higher than in group B（P〈0.01）, while SOD level[（96.0±7.0） U/ml] was lower than in group B （P〈0.01）. The step-down latent time of group A was longer and the number of error in Y-maze was more than B group （P〈 0.01）. NR2B mRNA level and NR2B protein expression in the hippocampi of group A rats were evidently lower than that in group B （P〈0.01）. NR2B immunohistoehemical level was lower in the CA1 area of the hippocampi of group A rats than that of the group B （P〈 0.01）. Conclusions Cognitive function were decreased in cirrhotic portal hypertension rats, with decreasing NR2B mRNA and protein expression level in the hippocampus as well.

关 键 词：肝硬化 门静脉高压 认知功能 N-甲基-D-天门冬氨酸受体2B亚基 大鼠 

分 类 号：R575.2[医药卫生—消化系统]