神经药理学报 ›› 2015, Vol. 5 ›› Issue (6): 1-5.

• 研究论文 •    下一篇

缺血预处理对脑缺血再灌注损伤保护作用的实验研究

张婧1,邹玉安2,董晓华1,马飞1,王欢欢1   

  1. 1.河北北方学院研究生院,张家口,075000,中国
    2.河北北方学院附属第一医院神经内科,张家口,075000,中国
  • 出版日期:2015-12-26 发布日期:2016-03-03
  • 通讯作者: 邹玉安,主任医师,硕士生导师; E-mail: zya8857111@sohu.com
  • 作者简介:张婧,女,硕士研究生;研究方向:缺血性脑血管病;E-mail:18832353811@163.com
  • 基金资助:

    河北省医学科学研究重点课题计划(No.20150054),河北省高等学校科学技术研究重点项目(No.ZD2014065)

Experimental Study on Protective Effect of Ischemic Preconditioning on Ischemia-Reperfusion Injury

ZHANG Jing1, ZOU Yu-an2, DONG Xiao-hua1, MA Fei1, WANG Huan-huan1   

  1. 1. Graduate Division, Hebei North University, Zhangjiakou, 075000, China
    2. Department of Neurology, the First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, China
  • Online:2015-12-26 Published:2016-03-03
  • Contact: 邹玉安,主任医师,硕士生导师; E-mail: zya8857111@sohu.com
  • About author:张婧,女,硕士研究生;研究方向:缺血性脑血管病;E-mail:18832353811@163.com
  • Supported by:

    河北省医学科学研究重点课题计划(No.20150054),河北省高等学校科学技术研究重点项目(No.ZD2014065)

摘要: 目的:通过观察Toll样受体4(Toll-like receptors,TLR4)和肿瘤坏死因子-α(TNF-α)的表达变化,探讨缺血预处理对大鼠再灌注损伤的保护作用并研究其意义。方法:将36只SPF级健康雄性SD大鼠随机分为缺血预处理组(CIP组n=12)、缺血再灌注组(I/R组n=12)和假手术组(Sham组n=12);I/R组采用线栓法阻断大脑中动脉(MCAO)2h建立模型,CIP组先给予MCAO阻断10 min,再灌注72 h后给予与I/R组相同的处理,假手术组仅分离血管。均于术后1d取材检测脑梗死体积、用 Zea Longa评分标准进行神经功能评分以及通过荧光实时定量PCR(Real-time Quantitative polymerase chain reaction)法测定TLR4和TNF-α mRNA水平的表达。结果:缺血再灌注后1 d各组大鼠比较,CIP组大鼠脑梗死体积明显低于I/R组,差异有显著统计学意义(P<0.05),CIP组大鼠的神经功能缺损评分明显低于I/R组,二者比较有显著性差异(P<0.05)。TLR4、TNF-α mRNA在CIP组与I/R组的表达明显高于Sham组,差异有显著统计学意义(P<0.05,P<0.01),而二者在CIP组的表达明显低于I/R组(P<0.05)。结论:缺血预处理能改善由再灌注损伤引起的功能障碍,可能通过下调促炎因子的表达来减轻脑组织缺血再灌注损伤,从而减轻炎症反应。

关键词: 缺血预处理, 缺血再灌注损伤, Toll样受体4, TNF-&, alpha

Abstract: Objective: Explore the protection of cerebral ischemic preconditioning on ischemia-reperfusion injury by observing the expression changes of TLR4 and TNF-α in cerebral cortex of rats, further investigate its signification. Methods: Thirty six SPF healthy male SD rats were assigned randomly into 3 group: cerebral ischemic preconditioning group (CIP group, n=12), ischemia-reperfusion group (I/R group, n=12),and sham group (Sham group, n=12 ).The I/R group were subjected to 2 hours of right middle cerebral artery occlusion (MCAO) reperfusion with suture-occluded method to establish focal cerebral ischemia reperfusion injury model. 10 miniutes MCAO by suture-occluded was uesd as CIP, 72 hours after reperfusion, given the same treatment like the I/R group. For the Sham group, separate the carotid artery only. One day after surgery, the animals were sacrificed. The infarction volume was evaluated by the method of TTC staining, the neural behavioral score were measured by Zea Longa assessment criteria and the expression levels of TLR4 and TNF-α mRNA were assessed by the method of real-time quantitative PCR. Results: Comparison of rats in 1 d after ischemia, the infarct volume in CIP group was lower than I/R group, the difference was statistically significant (P<0.05). Compared with I/R group, the neural behavioral scores of CIP group were significantly reduced, there exists significant differences(P<0.05). The mRNA expression of TLR4 and TNF-α in CIP group and I/R group were both apparently higher than the sham group (P<0.05,P<0.01), the expression of both in CIP group were significantly lower than the I/R group(P<0.05). Conclusion: Cerebral ischemic preconditioning can ameliorate the dysfunction produced by ischemia-reperfusion injury, and the ischemia reperfusion injury of brain tissue may be alleviated by down regulating the expression of proinflammatory factors, which could alleviate the inflammatory response.

Key words: ischemic preconditioning, ischemia-reperfusion injury, Toll-like receptors 4 (TLR4), tumor necrosis factor-&, alpha, (TNF-&, alpha, )

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