摘要
目的:研究髓样分化因子88抑制肽(MIP)对小鼠脑缺血损伤的保护作用及其机制。方法:将45只C57BL/6小鼠随机分为假手术组(sham)、局灶性脑缺血组(FCI)和给药组(MIP)。用光化学法诱导小鼠脑缺血损伤,给药组在缺血后第2 d开始给予MIP腹腔注射,10 mg/kg·d,连续3 d。分别于缺血后1、3、7和14 d观察前肢运动功能的变化,用HE染色观察梗死体积的变化,TUNEL染色检测缺血损伤区神经元凋亡,免疫荧光染色和Western Blot检测损伤区BDNF的表达。结果:与sham组相比,FCI组小鼠前肢运动能力明显下降(P <0.01),损伤区可见大量TUNEL阳性细胞;与FCI组相比,MIP组小鼠在脑缺血后第7 d,前肢运动功能显著改善(P <0.01);梗死体积明显减小(P <0.05),损伤区TUNEL阳性细胞的数量明显减少(P <0.01),而BDNF的表达显著上调(P <0.01)。结论:MIP对小鼠脑缺血损伤具有保护作用,其机制可能与其减少神经元凋亡,增加局部BDNF的表达有关。
Objective: To investigate the protective effect and mechanism of the myeloid differentiation factor 88 inhibitory peptide(MIP) on cerebral ischemic injury in mice.Methods: Forty-five C57 BL/6 mice were randomly divided into sham group,focal cortical ischemia group(FCI),and treatment group(MIP).Photochemically induced cerebral ischemia in mice,MIP was intraperitoneal injection of 10 mg/kg once a day for 3 consecutive days started from the on the 2 nd day after the modeling.The functional changes of forelimb locomotion were observed respectively on 1,3,7 and 14 d after ischemia.The infarct volume was observed and measured by HE staining.The neuronal apoptosis around the ischemic injury area was tested by TUNEL staining.The expression of BDNF in the lesion was detected by immunofluorescence staining and Western Blot.Results: Compared with sham group,the forelimb movement ability of mice in FCI group decreased significantly(P < 0.01),and a large number of TUNEL positive cells were observed in the damage area.Compared with FCI group,the motor function of mice in MIP group was significantly improved on day 7 after cerebral ischemia(P < 0.01),and infarct volume decreased significantly(P < 0.05) compared with FCI group.Besides,the number of TUNEL positive cells decreased dramatically around the injury area(P < 0.01),and the expression of BDNF in the lesion was obviously up-regulated(P < 0.01) in the MIP group.Conclusion: MIP have neuroprotective effects on cortical ischemic injury in mice,and its mechanism may be related to the decrease neuronal apoptosis and the increase of BDNF expression.
作者
杨吉平
王亚周
武胜昔
费琳
苟兴春
Yang Jiping;Wang Yazhou;Wu Shengxi;Fei Lin;Gou Xingchun(Institute of Basic Medical Sciences,Shaanxi Key Laboratory of Ischemic Cardiovascular Disease,and Shaanxi Key Laboratory of Brain Disorders,Xi'an Medical University,Xi'an 710021;Department of Neurobiology,School of Basic Medicine,Air Force Military Medical University,Xi'an 710032;Departments of Psychiatry and Psychology,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)
出处
《神经解剖学杂志》
CAS
CSCD
北大核心
2020年第5期493-500,共8页
Chinese Journal of Neuroanatomy
基金
国家自然科学基金资助项目(81971330)
陕西省教育厅重点实验室项目(19JS061)
西安医学院国家基金培育项目(2017GJFY22)。