南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (09): 1359-1364.doi: 10.12122/j.issn.1673-4254.2020.09.21

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亚低温治疗对脑出血模型大鼠动物行为学的影响及其机制

彭 羽，林 赟，侯晓林，廖晓灵，刘进平   

  • 出版日期:2020-09-20 发布日期:2020-09-20

Effect of mild hypothermia on behaviors of rats with intracerebral hemorrhage and the possible mechanism

  • Online:2020-09-20 Published:2020-09-20

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摘要： 目的 探讨亚低温治疗对脑出血大鼠脑组织炎症反应及血管新生的影响，分析其改善脑出血大鼠动物行为学的可能作用机制。方法 将120只健康雄性SD大鼠随机分为假手术组、脑出血组、亚低温组，40只/组。脑出血组、亚低温组：采用立体定向注射自体血的方法建立脑出血动物模型；假手术组：注入等体积生理盐水。亚低温组建模成功后15 min给予亚低温（30~32 ℃）干预8 h后复温（37~38 ℃），假手术组、脑出血组体温控制37~38 ℃。治疗2、4、7、14及21 d，采用Longa评分法、平衡木评分法、Berderson评分法评估大鼠动物行为学；采用免疫组化法检测大鼠脑组织肿瘤坏死因子-α（TNF-α）、兔核转录因子-κB（NF-κB）蛋白表达；采用RT-PCR法检测缺氧诱导因子-1α（HIF1-α）、血管内皮生长因子（VEGF）mRNA表达。结果 治疗2、4、7、14、21 d，脑 出血组、亚低温组脑出血大鼠动物行为学评分高于假手术组（P<0.05，P<0.01），脑组织TNF-α、NF-κB蛋白表达高于假手术组（P<0.01），脑组织HIF1-α mRNA、VEGF mRNA表达高于假手术组（P<0.01）；亚低温组脑出血大鼠动物行为学评分低于脑出血组（P<0.05），脑组织TNF-α、NF-κB蛋白表达低于脑出血组（P<0.01），脑组织HIF1-α mRNA、VEGF mRNA表达高于脑出血组（P<0.05，P<0.01）。结论 亚低温治疗能够改善脑出血模型大鼠动物行为学，可能与拮抗脑组织炎症反应、促进血管新生等因素有关。

关键词: 脑出血, 亚低温, 动物行为学, 炎症反应, 血管新生

Abstract: Objective To explore the effect of mild hypothermia on inflammatory response and angiogenesis in brain tissues of rats with intracerebral hemorrhage (ICH) and its possible mechanism for improving behavioral deficits of the rats After ICH. Methods A total of 120 healthy male SD rats were randomly divided into sham operation group, ICH group and mild hypothermia group. Rat models of ICH were established in the latter two groups by stereotactic injection of autogenous blood in the brain, and the rats in the sham operation group received injection of normal saline in the same manner. At 15 min after modeling, the rats in hypothermia group were subjected to mild hypothermia (30-32 ℃) for 8 h followed by rewarming (37- 38 ℃); the body temperature was maintained at 37-38 ℃ in the other two groups. At 2, 4, 7, 14 and 21 days after the treatment, Longa scoring, balance beam scoring and Berderson scoring were used to evaluate the behavioral deficits of the rats. Immunohistochemical staining was used to detect the protein expressions of tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in the brain tissue of the rats, and the mRNA expressions of α subunit of hypoxia-inducible factor 1 (HIF1-α) and vascular endothelial growth factor (VEGF) were detected using RT- PCR. Results At 2, 4, 7, 14 and 21 days after the treatment, the behavioral scores of the rats were significantly higher in ICH group and mild induced hypothermia group than in the sham operation group (P<0.05 or 0.01). The protein expressions of TNF-α and NF-κB and mRNA expressions of HIF1-α and VEGF were significantly higher in ICH group and mild hypothermia group than in the sham operation group (P<0.01). The behavioral scores were significantly lower in mild hypothermia group than in ICH group (P<0.05), and the protein expressions of TNF-α and NF-κB were lower and the mRNA expressions of HIF1- α and VEGF were higher in mild hypothermia group than in ICH group (P<0.05 or 0.01). Conclusion Mild hypothermia can improve behavioral deficits in rats with ICH possibly by antagonizing brain inflammation and promoting angiogenesis.

Key words: intracerebral hemorrhage, mild hypothermia, animal ethology, inflammatory response, angiogenesis