高渗盐水保护血脑屏障减轻脑出血大鼠脑水肿的相关机制研究

doi:10.12300/j.issn.1674-5817.2020.140

摘要/Abstract

摘要： 目的探讨高渗盐水治疗减轻脑出血模型大鼠脑水肿的相关机制。方法 60只雄性SD大鼠随机分为对照组、模型组和治疗组。在大鼠脑实质注射胎牛血清制作脑出血大鼠模型后,治疗组大鼠经尾静脉泵入10%高渗盐水,0.3 mL/h,共48 h。对比各组大鼠死亡率,取脑组织,肉眼观察其外观与病理学变化;同时,测定各组大鼠的脑含水量、脑组织中基质金属蛋白酶-9（matrix metalloproteinase-9,MMP-9）与基质金属蛋白酶组织抑制剂-1（metallopeptidase inhibitor-1,TIMP-1）比例,以及相关紧密连接蛋白claudins、occludin和zonula occludens-1（ZO-1）表达的差异。结果模型组大鼠死亡率和脑组织含水量均明显高于治疗组（均P<0.05）。肉眼观察显示,模型组大鼠脑中线明显从病灶侧移向对侧,治疗组大鼠脑中线未见偏移。显微镜下,治疗组大鼠脑组织水肿明显减轻,炎性细胞渗出明显减少。另外,治疗组大鼠脑组织中MMP-9/TIMP-1比例明显低于模型组,而紧密连接蛋白claudin-5、occludin以及ZO-1均高于模型组（均P<0.05）。结论高渗盐水可通过降低MMP-9/TIMP-1比例,稳定紧密连接蛋白claudin-5、occludin以及ZO-1的表达,维持血脑屏障结构完整性,改善脑出血后脑水肿的严重程度,从而降低实验模型大鼠的死亡率。

关键词: 基质金属蛋白酶-9, 基质金属蛋白酶组织抑制剂-1, 紧密连接蛋白, 血脑屏障, 脑出血, 大鼠

Abstract: Objective To investigate the mechanism of hypertonic saline (HS) treatment to reduce cerebral edema in intracerebral hemorrhage (ICH) rats by. Methods Sixty male SD rats were randomly divided into control, model, and treatment groups. An ICH rat model was established by injecting fetal bovine serum (FBS) into the brain parenchyma of rats. The rats in the treatment group were injected with 0.3 mL/h 10% HS via the tail vein for 48 h. The mortality of the rats was compared between the groups. Brain tissues were collected to observe the morphological and pathological changes, detect the water content differences in the brain, and measure the ratio of matrix metalloproteinase-9 (MMP-9) to tissue inhibitor of metalloproteinases-1 (TIMP-1) and the expression of related tight junction proteins, including claudins, occludin, and zonula occludens-1 (ZO-1). Results The mortality and water content of the brain tissues in the model group were significantly higher than those in the treatment group (all P < 0.05). The naked eye observation showed that the midline of the brain in the model group shifted from the lesion side to the contralateral side, while the midline of the brain in the treatment group did not. The ratio of MMP-9/TIMP-1 in the brain tissue of rats in the treatment group was significantly lower than that in the model group, while the tight junction proteins of claudin-5, occludin, and ZO-1 in the brain tissue of rats in the treatment group were higher than those in the model group (all P < 0.05). Conclusion HS can maintain the structural integrity of the blood-brain barrier by reducing the ratio of MMP-9/TIMP-1, stably and tightly connecting the expression of claudin-5, occludin, and ZO-1, thereby improving the severity of brain edema after ICH and reducing the mortality of experimental model rats.

Key words: Matrix metalloproteinase-9, Tissue inhibitor of metalloproteinases-1, Tight Junction, Blood brain barrier, Intracerebral hemorrhage, Rats

中图分类号:

Q95-33

第五飞虎, 赵志靖, 邓毅恒. 高渗盐水保护血脑屏障减轻脑出血大鼠脑水肿的相关机制研究[J]. 实验动物与比较医学, 2021, 41(4): 327-332.

DIWU Feihu, ZHAO Zhijing, DENG Yiheng. Mechanism of Hypertonic Saline to Reduce Cerebral Edema in Rats with Cerebral Hemorrhage by Protecting Blood-brain Barrier[J]. Laboratory Animal and Comparative Medicine, 2021, 41(4): 327-332.

图/表 3

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