抑制PTEN对大鼠脑缺氧损伤后GluR2表达及认知功能的影响研究
Effects of PTEN Inhibition on Expression of GluR2 and Cognitive Function after Brain Hypoxia Injury in Rats
李玲 1杨婷 1李健 1陈睿 1孙玲 1王凡 2刘媛3
作者信息
- 1. 中国人民解放军联勤保障部队第九二五医院神经内科,贵阳 550004
- 2. 贵州医科大学白云附属医院,贵阳 550001
- 3. 陆军军医大学大坪医院特殊环境战伤防治研究室,创伤烧伤与复合伤国家重点实验室,重庆 400042
- 折叠
摘要
目的 探讨抑制第10号染色体同源丢失性磷酸酶张力蛋白基因(PTEN)对大鼠脑缺氧损伤后海马神经元谷氨酸受体2亚单位(GluR2)表达及机体认知功能的影响.方法 成年雄性SD大鼠60只,随机分为正常组、缺氧损伤组(伤前2周侧脑室注射0.9%氯化钠溶液)和PTEN干预组(伤前2周侧脑室注射PTEN siRNA),每组均n=20.缺氧损伤组和干预组大鼠放入模拟海拔6 000 m的低压氧舱中7 d.伤后不同时间点对大鼠进行水迷宫、穿梭箱检测,并通过β-tublinⅢ免疫荧光染色观察海马神经元存活率,Western blot检测GluR2表达变化.结果 伤后7 d PTEN干预组和缺氧损伤组海马CA1区β-tublinⅢ阳性神经元数量较正常组明显减少,但PTEN干预组神经元数量显著多于缺氧损伤组(P<0.05).PTEN干预组伤后1和3 d GluR2表达水平较缺氧损伤组显著升高(P<0.05).PTEN干预组在伤后寻靶时间、主动及被动穿梭的比例均优于缺氧损伤组(均P<0.05).结论 脑损伤后抑制PTEN可通过增加GluR2表达水平,促进脑缺氧损伤后海马神经元的存活,改善认知损害.
Abstract
Aim To observe the effects of phosphatase and tensin homology deleted on chromosome ten(PTEN)inhibition on expression of GluR2 and cognitive function after cerebral hypoxia injury in rats.Methods Sixty adult male SD rats of 250～280 g were randomly divided into a normal group,an injury group,and a PTEN intervention group,with 20 rats in each group.The PTEN intervention group was injected with PTEN siRNA in the paracele 2 weeks before injury and the injury group was injected with the same amount of saline.The rats of injury and intervention groups were placed in a simulated low-pressure oxygen chamber at an altitude of 6 000 meters for 7 days.After injury,rats were subjected to water maze and shuttle box tests at different time points.The survival of hippocampal neurons was observed by β-tublin Ⅲ immunofluorescence staining.The expression of GluR2 was detected by Western blot.Results Compared with the injury group,the number of β-tublin Ⅲ positive cells(neurons)in the CA1 area of hippocampus in PTEN intervention group was significantly more than that in injured group(P<0.05)at 7 days after injury.The expression of GluR2 in PTEN intervention group significantly increased at 1 and 3 days after injury(P<0.05).The rats in PTEN intervention group had shorter target seeking time and better proportion of active and passive shuttle compared to the injury group post injury,which had significant difference in statistics(P<0.05).Conclusion Inhibition of PTEN can promote the survival of hippocampal neurons after cerebral hypoxia injury and improve the cognitive dysfunction by increasing the expression of GluR2.
关键词
缺氧损伤/认知损害/第10号染色体同源丢失性磷酸酶张力蛋白基因/谷氨酸受体2亚单位Key words
hypoxia injury/cognitive impairment/phosphatase and tensin homology deleted on chromosome ten/glutamate receptor 2 subunit引用本文复制引用
出版年
2024
NETL
NSTL
万方数据