基础医学与临床 ›› 2022, Vol. 42 ›› Issue (1): 100-105.

• 研究论文 • 上一篇    下一篇

呋塞米对脑出血模型大鼠PERK/eIF2α/CHOP通路及继发性脑损伤的影响

张瑜1,高建洲2,韩韶2   

  1. 1. 邯郸市第一医院东院区
    2. 邯郸市第一医院
  • 收稿日期:2020-12-07 修回日期:2021-04-27 出版日期:2022-01-05 发布日期:2022-01-05
  • 通讯作者: 张瑜 E-mail:li40sy@163.com
  • 基金资助:
    河北省2020年度医学科学研究计划项目

Effects of furosemide on PERK/eIF2α/CHOP pathway and secondary brain injury in rat models with intracerebral hemorrhage

  • Received:2020-12-07 Revised:2021-04-27 Online:2022-01-05 Published:2022-01-05

摘要: 目的:探讨呋塞米对脑出血(ICH)大鼠PERK/eIF2α/CHOP通路及继发性脑损伤的影响。方法:采用脑定位注射Ⅳ型胶原酶的方法建立ICH大鼠模型,随机分为模型组、呋塞米低剂量组、呋塞米中剂量组、呋塞米高剂量组、神经节苷脂组,每组18只,另外选取18只SD大鼠设为假手术组。药物处理后,对各组大鼠神经功能缺损进行评分;测量脑组织含水量;采用Evans蓝外渗实验检测大鼠血脑屏障损伤;采用HE染色检测大鼠海马神经元损伤情况;采用酶联免疫吸附法(ELISA)检测大鼠血清干扰素-γ(IFN-γ)、白细胞介素-6(IL-6)水平;采用免疫印迹法检测大鼠脑组织PERK/eIF2α/CHOP通路相关蛋白p-PERK/PERK、p-eIF2α/eIF2α、CHOP表达情况。结果:相比假手术组,模型组大鼠海马神经元变性坏死,皱缩变小,数目明显减少,呈现严重病理损伤,神经功能缺损评分、脑组织含水量、Evans蓝渗出量、血清IFN-γ及IL-6水平、p-PERK/PERK、p-eIF2α/eIF2α、CHOP表达水平明显升高(P<0.05)。相比模型组,呋塞米低、中、高剂量组及神经节苷脂组大鼠海马神经元病理损伤均减轻,神经功能缺损评分、脑组织含水量、Evans蓝渗出量、血清IFN-γ及IL-6水平、p-PERK/PERK、p-eIF2α/eIF2α、CHOP表达水平均降低(P<0.05),且呋塞米各组呈剂量依赖性,相比神经节苷脂组,呋塞米高剂量组大鼠各指标无明显变化(P>0.05)。结论:呋塞米可下调PERK/eIF2α/CHOP通路蛋白表达,缓解脑水肿及海马神经元损伤,修复ICH大鼠神经功能。

关键词: 呋塞米, 脑出血, PERK/eIF2α/CHOP通路, 脑损伤

Abstract: Objective: To investigate the effects of furosemide on PERK/eIF2α/CHOP pathway and secondary brain injury in rats with intracerebral hemorrhage (ICH). Methods: ICH rat model was established by intracerebral injection of collagenase type IV, and the rats were randomly divided into model group, low-dose furosemide group, medium dose furosemide group, high-dose furosemide group and ganglioside group, with eighteen rats in each group, another eighteen SD rats were selected as sham operation group. After drug treatment, the neurological deficits of rats in each group were scored; the water content of brain tissue was measured; Evans blue extravasation test was used to detect the blood-brain barrier injury; HE staining was used to detect the damage of hippocampal neurons; enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of interferon-γ (IFN-γ) and interleukin-6 (IL-6); Western blot was used to detect the expression of p-PERK/PERK, p-eIF2α/eIF2α and CHOP. Results: Compared with those in the sham operation group, the hippocampal neurons in the model group were degenerated and necrotic, the shrinkage was smaller, the number was significantly decreased, severe pathological damage was found, the neurological deficit score, brain water content, Evans blue exudation, levels of serum IFN-γ and IL-6, expression levels of p-PERK/PERK, p-eIF2α/eIF2α and CHOP were significantly increased (P < 0.05). Compared with those in the model group, the pathological damage of hippocampal neurons in the low, medium and high dose furosemide groups and ganglioside group were reduced, the neurological deficit score, brain water content, Evans blue exudation, levels of serum IFN-γ and IL-6, expression levels of p-PERK/PERK, p-eIF2α/eIF2α and CHOP were decreased (P < 0.05), furosemide groups were dose-dependent, and there was no significant change in each index between furosemide high-dose group and ganglioside group (P > 0.05). Conclusion: Furosemide can down-regulate the expression of PERK/eIF2α/CHOP pathway protein, relieve brain edema and hippocampal neuron damage, and repair the neural function of ICH rats.

Key words: furosemide, intracerebral hemorrhage, PERK/eIF2α/CHOP pathway, brain injury