阿托伐他汀对局灶性脑缺血大鼠脑水肿的影响及机制探讨  

Effect of atorvastatin on brain edema and its mechanism in rats after focal cerebral ischemia

作　　者：杨会杰[1] 王金兰[1] 乐婷[1] 程宝仓 安颖[1] 

机构地区：[1]郑州大学第二附属医院神经内科,郑州450014

出　　处：《中华神经医学杂志》2016年第2期130-135,共6页Chinese Journal of Neuromedicine

基　　金：郑州大学第二附属医院院内基金 Fund from Second Affiliated Hospital of Zhengzhou University

摘　　要：目的观察局灶性脑缺血大鼠脑水肿、肿瘤坏死因子-d（TNF-a）及水通道蛋白-4（AQP-4）的动态变化．并探讨阿托伐他汀对脑水肿的影响及作用机制。方法108只雄性SD大鼠按随机数字表法分为假手术组、模型组、治疗组，每组36只；每组又按观察时间点不同分为1d亚组、3d亚组、7d亚组，每亚组12只。模型组和治疗组采用大啮中动脉栓塞法制备局灶性魑缺血模型，假手术组只分离血管，不结扎、不插线。建模成功后治疗组给予阿托伐他汀[4mg／（kg·d）]灌胃，分别持续至各观察时间点；其余2组在相应时间点给予等量生理盐水灌胃。采用干湿重法检测各观察时间点每组大鼠的脑组织含水量．采用RT—PCR检测TNF-a、AQe-4mRNA表达水平，采用Westernblotting检测AQP-4蛋白表达水平。结果在相同观察时间点，与假手术组相比，模型组和治疗组脑组织含水量、TNF-a mRNA表达水平、A9P_4mRNA表达水平及AQP-4蛋白表达水平均明显增高，差异均有统计学意义（P〈O．05）；与模型组相比，治疗组脑组织含水量、TNF-a mRNA表达水平、AQP-4mRNA表达水平及AQP-4蛋白表达水均明显降低，差异均有统计学意义（P〈0．05）。结论局灶性脑缺血大鼠的脑水肿与TNF-a诱导ApP-4mRNA和蛋白表达上升相关；阿托伐他汀能通过抑制TNF—d使AQp-4 mRNA和蛋白表达下调，减轻脑水肿，从而起到脑保护作用。Objective To observe the dynamic changes of brain edema, tumor necrosis factor-a （TNF-a）, aquaporin-4 （AQP-4） in focal cerebral ischemia rats and investigate the effect of atorvastatin on the above-mentioned factors. Methods One hundred and eight male SD rats were randomly divided into sham-operated group, model group and treatment group （n=36）; furthermore, each group was divided into three subgroups： 1 d group, 3 d group and 7 d group （n=12）. Focal cerebral ischemia models in model group and treatment group were induced by left middle cerebral artery occlusion, while rats in the sham-operated group were only separated from blood vessels with no ligation and no inserted line. After succeeded models, the treatment group received gavage administration of atorvastatin （4 mg/ [kg- d]）, others were given the same dosage of normal saline at the same time. The brain edema was calculated by measuring brain water content via dry-wet method, and the mRNA expressions of TNF-a and A QP-4 were detected by real time-PCR; Westem blotting was employed to detect the AQP-4 protein expression. Results At the same observation time, as compared with those in the sham-operated group, the brain water content, TNF-a mRNA expression and A QP-4 mRNA and protein expressions in the model group and treatment group markedly increased （P〈0.05）; as compared with the model group, treatment group had statistically decreased brain water content, TNF-a mRNA expression and A QP-4 mRNA and protein expressions （P〈O.05）. Conclusion The brain edema of focal cerebral ischemia rats may be positively correlated to A QP-4 mRNA and protein expressions induced by TNF-a; atorvastatin probablydown-regulates A QP-4 mRNA and protein expressions by inhibiting TNF-a to alleviate brain edema and protect brain tissues.

关 键 词：阿托伐他汀 局灶性脑缺血 脑水肿 肿瘤坏死因子-A 水通道蛋白4 

分 类 号：R965[医药卫生—药理学]