| 张纵横,朱全智,丁蕾.核因子2 相关因子2 激动剂dh404 对异氟醚诱导认知功能障碍大鼠脑海马组织的影响[J].安徽医药,2023,27(3):597-601. |
| 核因子2 相关因子2 激动剂dh404 对异氟醚诱导认知功能障碍大鼠脑海马组织的影响 |
| Effect of Nuclear factor erythroid 2-related factor 2 agonist on the hippocampus of rats with isoflurane induced cognitive impairment |
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| DOI：10.3969/j.issn.1009-6469.2023.03.039 |
| 中文关键词: 认知功能障碍 异氟醚 核因子2相关因子2信号通路 Nrf2激动剂dh404 大鼠，Sprague-Dawley |
| 英文关键词: Cognitive impairment Isoflurane Nrf2 signaling pathway The NRF2 activator DH404 Rats, Sprague-Dawley |
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| 中文摘要: |
| 目的 探讨核因子2相关因子2(Nrf2)激动剂激活Nrf2信号通路后对异氟醚诱导认知功能障碍大鼠脑海马组织的影响。方法 该研究起止时间为2018年12月至2019年8月。选择清洁级SD雄性大鼠24只，按照随机数字表法分为三组:对照组、异氟醚组、Nrf2激动剂dh404+异氟醚组(dh404组)，每组8只。dh404组在吸入异氟醚前30 min腹腔注射Nrf2激动剂dh404(1.5 mg/kg)，对照组和异氟醚组注射等量的生理盐水。麻醉结束后24 h后各组大鼠进行Morris水迷宫测试；测试结束后立即处死大鼠，取脑海马组织。采用免疫组织化学法检测各组大鼠脑海马组织Nrf2表达情况；采用蛋白质印迹法检测各组大鼠脑组织中血氧合酶1(HO-1)、Kelch 样环氧氯丙烷相关蛋白1(Keap1)的蛋白表达；采用实时荧光定量逆转录聚合酶链反应(qRT-PCR)检测各组大鼠Nrf2、HO-1、Keap1的mRNA表达水平；采用TBA法检测丙二醛；采用WST-1法检测超氧化物歧化酶(SOD)；采用分光光度法检测谷胱甘肽过氧化物酶(GSH-Px)的表达水平。结果 与对照组相比，异氟醚组大鼠逃避潜伏期长，平台所在象限停留时间及穿越平台次数减少(P<0.05)；dh404组大鼠相关指标有所改善。dh404组大鼠脑组织Nrf2mRNA 表达水平(6.70±0.98)高于对照组(1.00±0.12)及异氟醚组(1.16±0.15)(P<0.05)，而异氟醚组与对照组相比，Nrf2mRNA表达水平差异无统计学意义(P>0.05)。与对照组相比，异氟醚组和dh404组大鼠脑组织Keap1表达水平显著升高、丙二醛浓度显著增加而HO-1表达水平显著减少、SOD、GSH-Px活性降低(P<0.05)；与异氟醚组相比，dh404组大鼠Keap1表达水平减少、丙二醛浓度明显减少而HO-1表达水平明显升高、SOD、GSH-Px活性明显增强(P<0.05)。结论 促进Nrf2信号通路激活可改善异氟醚6 h吸入导致的大鼠认知功能损害。 |
| 英文摘要: |
| Objective To investigate the effect of nuclear factor erythroid 2-related factor 2 (Nrf2) agonist activating Nrf2 signal pathway on the hippocampus of rats with isoflurane induced cognitive impairment.Methods This study starts and ends from Decem?ber 2018 to August 2019. Twenty-four male SD rats of clean grade were randomly divided into three groups according to the random number table: control group, isoflurane group and Nrf2 agonist dh404 + isoflurane group (dh404 group), with 8 rats in each group. Nrf2 agonist dh404 (1.5 mg/kg) was intraperitoneally injected 30 minutes before isoflurane inhalation in the dh404 group, and the control group and the isoflurane group were injected with the same amount of normal saline. Morris water maze test was performed 24 hours af?ter anesthesia, and rats were killed immediately after the test, and the hippocampal tissue was taken. The expression of Nrf2 in hippo?campus was detected by immunohistochemistry. Protein expression of hemeoxygenase-1(HO-1) and Kelch-like epichlorohydrin-related protein 1 (Keap1) in brain tissues of rats in each group were detected by Western Blot. The mRNA expression of Nrf2, HO-1 and Keap 1 were detected by qRT-PCR. Malondialdehyde (MDA) was detected by TBA, superoxide dismutase (SOD) by WST-1 and glutathione peroxidase (GSH-Px) by spectrophotometry.Results Compared with the control group, the escape latency of rats in isoflurane group was longer, the residence time of platform quadrant and the number of times of crossing platform were reduced, the difference was sta?tistically significant (P<0.05). Related indexes of rats in dh404 group were improved. The mRNA expression level of Nrf2 in brain tis?sue in the dh404 group (6.70±0.98) was higher than that in the control group (1.00± 0.12) and the isoflurane group (1.16±0.15), the dif?ference was statistically significant (P<0.05). Compared with the control group, the expression levels of Keap1 and MDA in brain tissue of rats in isoflurane group and dh404 group increased significantly, while the expression level of HO-1 decreased significantly, and the activities of SOD and GSH-Px decreased significantly (P<0.05). Compared with the isoflurane group, the expression levels of Keap1 and MDA in dh404 group decreased significantly, the expression levels of HO-1 increased significantly, and the activities of SOD and GSH-Px increased significantly (P<0.05).Conclusion Promoting the activation of Nrf2 signaling pathway can improve the cognitive impairment caused by isoflurane cognitive inhalation for 6h in rats. |
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