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葫芦素 E 通过调节 NF-κB 通路减轻七氟醚诱导的大鼠认知功能障碍。

Cucurbitacin E reduces the cognitive dysfunction induced by sevoflurane in rats by regulating NF-κB pathway.

机构信息

Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, China.

Department of Anesthesiology, Xi'an International Medical Center, Xi'an, China.

出版信息

Acta Biochim Pol. 2022 Jun 16;69(2):387-391. doi: 10.18388/abp.2020_5817.

DOI:10.18388/abp.2020_5817
PMID:35709303
Abstract

BACKGROUND

Perioperative neurocognitive disorders (PND) occur frequently and refer to alterations in cognitive function after surgery, especially in elderly patients. PND is characterized as abnormalities of learning, memory, language, and emotions. Cucurbitacin E has been reported to possess various pharmacological properties, including anticancer, antiviral, and anti-inflammatory effects. In this study, we investigated whether cucurbitacin E could alleviate sevoflurane-induced cognitive dysfunction in rats.

METHODS

Sprague-Dawley male rats (~6 weeks old) were randomly assigned to three groups: the control group, the Sevoflurane group, and the Sevoflurane + Cucurbitacin E group. Subsequently, the cognitive dysfunction of the rats was evaluated through the morris water maze test. Hematoxylin and eosin (HE) staining was used to measure the pathological change in brain tissues. Enzyme-linked immunosorbent assay (ELISA) kits were used for determinations of S-100 calcium binding protein B (S-100β) and neuron-specific enolase (NSE) and cytokine. Cell apoptosis was analyzed by TdT-Mediated Nick-End Labeling (TUNEL) staining. Protein levels were confirmed by Western blotting.

RESULTS

Cucurbitacin E relieved brain injury in rats induced by sevoflurane. Cucurbitacin E alleviated sevoflurane-induced S-100β and NSE levels. Additionally, the Morris water maze task revealed that cucurbitacin E attenuated cognition impairment in sevoflurane-induced rats. Sevoflurane increased levels of IL-6, TNF-α and IL-1β levels, and decreased the level of IL-10. However, cucurbitacin E exhibited opposite effects on these cytokines, which were induced by sevoflurane. Furthermore, cucurbitacin E inhibited sevoflurane-induced neuron apoptosis and NF-κB pathway in rats.

CONCLUSION

These findings indicate that cucurbitacin E can improve sevoflurane-induced cognitive dysfunction in rats by regulating NF-κB pathway, which provided a new strategy for PND treatment.

摘要

背景

围手术期神经认知障碍(PND)是指手术后认知功能的改变,尤其是在老年患者中。PND 的特征是学习、记忆、语言和情绪的异常。已报道葫芦素 E 具有多种药理特性,包括抗癌、抗病毒和抗炎作用。在本研究中,我们研究了葫芦素 E 是否可以减轻七氟醚诱导的大鼠认知功能障碍。

方法

将 Sprague-Dawley 雄性大鼠(~6 周龄)随机分为三组:对照组、七氟醚组和七氟醚+葫芦素 E 组。随后,通过 Morris 水迷宫试验评估大鼠的认知功能障碍。苏木精和伊红(HE)染色用于测量脑组织的病理变化。酶联免疫吸附试验(ELISA)试剂盒用于测定 S-100 钙结合蛋白 B(S-100β)和神经元特异性烯醇化酶(NSE)和细胞因子。TdT 介导的缺口末端标记(TUNEL)染色分析细胞凋亡。通过 Western blot 确认蛋白水平。

结果

葫芦素 E 减轻了七氟醚诱导的大鼠脑损伤。葫芦素 E 减轻了七氟醚诱导的 S-100β 和 NSE 水平。此外,Morris 水迷宫任务表明,葫芦素 E 减轻了七氟醚诱导的大鼠认知障碍。七氟醚增加了 IL-6、TNF-α 和 IL-1β 水平,并降低了 IL-10 水平。然而,葫芦素 E 对这些由七氟醚诱导的细胞因子表现出相反的作用。此外,葫芦素 E 抑制了七氟醚诱导的大鼠神经元凋亡和 NF-κB 通路。

结论

这些发现表明,葫芦素 E 通过调节 NF-κB 通路改善七氟醚诱导的大鼠认知功能障碍,为 PND 治疗提供了新策略。

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