解剖学报 ›› 2023, Vol. 54 ›› Issue (5): 505-511.doi: 10.16098/j.issn.0529-1356.2023.05.002

• 神经生物学 • 上一篇    下一篇

缺氧预处理通过缺氧诱导因子-1α/基质细胞衍生因子-1通路对大鼠血液学相关指标的影响

孙娟1* 陈敬威1 杨艺1 林涛1 牟雅琳2  赵秀丽1 曾国熙1 张艳3*    

  1. 1.青海大学附属医院神经内科,西宁 810001; 2.青海大学附属医院影像中心,西宁 810001;3.北京大学医学部基础医学院人体解剖学与组织学胚胎学系,北京 100083
  • 收稿日期:2022-04-21 修回日期:2022-05-07 出版日期:2023-10-06 发布日期:2023-12-25
  • 通讯作者: 孙娟 E-mail:sunjuan_128@163.com
  • 基金资助:
    高原低氧对蛛网膜下腔出血后早期脑损伤的作用及机制研究

Effects of hypoxia preconditioning on hematology-related indexes through hypoxia inducible factor-1α/stromal cell-derived factor-1 pathway in rats 

 SUN  Juan1* CHEN  Jing-wei YANG  Yi LIN  Tao1  MOU  Ya-lin2  ZHAO  Xiu-li1  ZENG  Guo-xi1  ZHANG  Yan3* 

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  1. 1.Department of Neurology, Qinghai University Affiliated Hospital, Xining 810001,China;   2.Department of Imaging Center, Qinghai University Affiliated Hospital, Xining 810001,China;   3.Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100083,China

  • Received:2022-04-21 Revised:2022-05-07 Online:2023-10-06 Published:2023-12-25
  • Contact: Juan Sun E-mail:sunjuan_128@163.com

摘要:

目的 探讨缺氧诱导因子-1α(HIF-1α)/基质细胞衍生因子-1 (SDF-1)通路对缺氧预处理大鼠模型的作用。方法 76只成年雄性SD大鼠,通过在低压氧舱(海拔5000 m)和西宁市(海拔2260 m)饲养建立缺氧预处理动物模型,随机分为6组:对照组(Ctrl 组),高海拔缺氧预处理1 d组(HHP-1d),高海拔缺氧预处理4 d组(HHP-4d)、高海拔缺氧预处理15 d组(HHP-15d),高海拔缺氧预处理30 d组(HHP-30d),中海拔缺氧预处理组(MHP),其中Ctrl组、HHP-4d组、HHP-30d组与MHP组利用7.0 T小动物MRI,T2加权像(T2WI)观察颅内结构及基底动脉直径,连续性自旋动脉标记(ASL)观察海马区及脑干区脑血流,检测各组大鼠血常规,ELISA检测各组大鼠血清HIF-1α和SDF-1浓度及血浆血小板活化因子(PAF)及P-选择素(SELP)浓度。
  结果 缺氧预处理条件下,颅内结构未见明显异常;基底动脉直径增宽,但无统计学意义;脑干区及海马区脑血流量明显升高,差异具有统计学意义(P<0.05),红细胞及白细胞升高,血小板下降,差异具有统计学意义(P<0.05),其中MHP组红细胞和血小板接近Ctrl组;缺氧预处理组HIF-1α浓度明显升高,SDF-1浓度(除HHP-1d组外)明显升高,HHP-1d、HHP-15d组PAF、SELP浓度明显升高,HHP-4d、HHP-30d组PAF浓度明显下降,HHP-4d组SELP浓度明显下降,差异均具有统计学意义(P<0.05)。   结论 缺氧预处理可通过HIF-1α/SDF-1通路增加机体氧储备量及免疫防御力,提高脑储备能力并发挥脑保护作用,其中以中海拔(海拔2260 m)饲养30 d预处理效果最佳。 

关键词:

Abstract:

 Objective To study the role of hypoxia inducible factor-1α (HIF-1α)/stromal cellderived factor-1 (SDF-1) pathway in high altitude  hypoxia preconditioning in rat.  Methods  Seventy-six adult male SD rats, which through fed in low-pressure oxygen chamber (altitude 5000 m) and Xining (altitude 2260 m) to establish the rat model of hypoxia preconditioning. Rats randomly divided into 6 groups: control group (Ctrl), high altitude hypoxic preconditioning 1 day group (HHP-1d), high altitude hypoxic preconditioning 4 days group (HHP-4d), high altitude hypoxic preconditioning 15 days group (HHP-15d), high altitude hypoxic preconditioning 30 days group (HHP-30d), medium altitude hypoxic preconditioning group (MHP). 7.0T small animal MRI was used to observe the intracranial structure, diameter of basilar artery and cerebral blood flow in the hippocampus and brainstem regions by the sequences of T2 weighted images (T2WI) and arterial spin labeling (ASL) in the groups of Ctrl, HHP-4d, HHP-30d and MHP. In each group, blood routine was tested, the concentrations of HIF-1α, SDF-1 in serum, platelet activating factor (PAF)and P-selectin (SELP) in plasma were detected by the method  of ELISA.  Results  In the hypoxia preconditioning groups, intracranial structure and diameter of basilar artery had no significant difference, while cerebral blood flow in the regions of brainstem and hippocampus increased significantly (P<0.05). Meanwhile, red blood cell and white blood cell increased significantly, while platelet decreased significantly in the groups of hypoxia preconditioning (P<0.05). Red blood cell and platelet in MHP group were closer to Ctrl group. The concentrations of HIF-1α and SDF-1 (except HHP-1d group) increased significantly in hypoxia preconditioning groups (P<0.05).The concentrations of PAF and SELP increased significantly in HHP-1d and HHP-15d groups. The concentration of PAF decreased significantly in the HHP-4d and HHP-30d groups, and SELP decreased significantly in HHP-4d group (P<0.05).  Conclusion Hypoxia preconditioning can increase oxygen storage and immune defense capacity, improve brain reserve capacity and play the effect of brain protection through HIF-1α/SDF-1 pathway. The best effect preconditioning was feed at medium altitude (altitude 2260 m) for 30 days.  

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