辛伐他汀对脑出血大鼠脑组织转录因子-κB以及肿瘤坏死因子α、白细胞介素1β表达的影响  

Effects of simvastatin on nuclear factor-kappaB,tumor necrosis factor α and interleukin 1β expressions in brain tissues of rats with intracerebral hemorrhage

作　　者：吴煜 罗曼 陈夏清 邹显巍[1] WU Yu;LUO Man;CHEN Xian-qing;ZOU Xian-wei(Department of Neurological Medicine,the First Affiliated Hospital of Chengdu Medical College,Chengdu 610500,China)

机构地区：[1]成都医学院第一附属医院神经内科,四川省成都市610500

出　　处：《广西医学》2018年第20期2437-2440,2447,共5页Guangxi Medical Journal

基　　金：四川省教育厅重点项目(17ZA0314);成都医学院第一附属医院课题(CYFY13DL-001)

摘　　要：目的探讨辛伐他汀对脑出血大鼠血肿周围组织中转录因子-κB(NF-κB)以及肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)表达的影响。方法将120只SD大鼠随机分为假手术组、脑出血组、治疗组,各40只。脑出血组和治疗组采用自体血立体定向注射法建立脑出血动物模型,假手术组于相同部位注射等量0. 9%氯化钠。治疗组于术后2 h行辛伐他汀(10 mg/kg)灌胃,假手术组与脑出血组给予等量0. 9%氯化钠灌胃。于造模后12 h、1 d、2 d、3 d、5 d分别处死各组大鼠留取脑组织,采用免疫组化法和免疫印迹法检测各组大鼠脑组织TNF-α、IL-1β及NF-κB的表达情况。结果各时间点,假手术组、治疗组尾状核周围脑组织的NF-κB、TNF-α、IL-1β蛋白表达量均低于脑出血组(均P <0. 05)。脑出血组大鼠血肿周围脑组织NF-κB的蛋白表达水平与TNF-α、IL-1β蛋白的表达水平均呈正相关(均P <0. 05)。各时间点,假手术组中尾状核周围脑组织可见少量NF-κB及TNF-α、IL-1β阳性细胞,而治疗组中的NF-κB、TNF-α、IL-1β阳性细胞较脑出血组明显减少。结论脑出血大鼠血肿周围脑组织高表达NF-κB、TNF-α、IL-1β;辛伐他汀治疗可通过下调NF-κB信号分子的表达,减少炎性细胞因子的产生,减轻脑出血后脑组织的炎症反应。Objective To investigate the effects of simvastatin on the nuclear factor-kappaB（NF-κB）,tumor necrosis factor α（TNF-α） and interleukin 1β（IL-1β） expressions in the tissues around the hematoma of rats with intracerebral hemorrhage. Methods A total of 120 SD rats were randomly divided into sham group,intracerebral hemorrhage group and treatment group,40 rats in each group.The animal model of intracerebral hemorrhage was established by stereotactic injection of autologous blood in the intracerebral hemorrhage group and treatment group.In the sham group,an equivalent volume of 0.9% sodium chloride was injected at the same site.Intragastric administration of simvastatin（10 mg/kg） was conducted in the treatment group at 2 hours after operation.At 12 hours,1,2,3 and 5 days after modeling,the rats were killed and their brain tissues were taken in each group.Immunohistochemistry and Western Blot were used to detect the expressions of TNF-α,IL-1β and NF-κB in the brain tissues of rats in each group. Results At each time point,the expressions of NF-κB,TNF-α and IL-1β in the brain tissues around ucleus laminaris in the sham group and treatment group were lower than those in the intracerebral hemorrhage group（all P 〈0.05）.In the tissues around the hematoma of rats in the intracerebral hemorrhage group,the expression of NF-κB protein positively correlated with the expression level of TNF-α and IL-1β proteins（all P 〈0.05）.At each time point, a small number of NF-κB,TNF-α and IL-1β positive cells were observed in brain tissues around ucleus laminaris in the sham group,while the treatment group got significantly decreased NF-κB,TNF-α and IL-1β positive cells than the intracerebral hemorrhage group. Conclusion NF-κB,TNF-α and IL-1β are highly expressed in the tissues around the hematoma of rats with intracerebral hemorrhage ;simvastatin can reduce the post-intracerebral hemorrhage inflammatory response of brain tissues by down-regulating the expression of NF-κB signaling mole

关 键 词：脑出血 辛伐他汀 转录因子-ΚB 肿瘤坏死因子Α 白细胞介素-1β 动物模型 大鼠 

分 类 号：R743.32[医药卫生—神经病学与精神病学]