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创伤性脑损伤中 HS、IGF-1 和 GH 的动态变化及其影响。

Dynamic Changes and Effects of HS, IGF-1, and GH in the Traumatic Brain Injury.

机构信息

Department of Neurosurgery, Yantai Yuhuangding Hospital, Yuhuangding East Road, Zhifu District, 264000, Yantai, Shandong, China.

出版信息

Biochem Genet. 2024 Oct;62(5):3821-3840. doi: 10.1007/s10528-023-10557-9. Epub 2024 Jan 17.

Abstract

The aim of this study was to examine the expression changes of HS, IGF-1, and GH in traumatic brain injury (TBI) patients and to detect their neuroprotective functions after TBI. In this study, we first collected cerebrospinal fluid (CSF) and plasma from TBI patients at different times after injury and evaluated the concentrations of HS, IGF-1, and GH. In vitro studies were using the scratch-induced injury model and cell-cell interaction model (HT22 hippocampal neurons co-cultured with LPS-induced BV2 microglia cells). In vivo studies were using the controlled cortical impact (CCI) model in mice. Cell viability was assessed by CCK-8 assay. Pro-inflammatory cytokines expression was determined by qRT-PCR, ELISA, and nitric oxide production. Western blot was performed to assess the expression of CBS, CSE, IGF-1, and GHRH. Moreover, the recovery of TBI mice was evaluated for behavioral function by applying the modified Neurological Severity Score (mNSS), the Rotarod test, and the Morris water maze. We discovered that serum HS, CSF HS, and serum IGF-1 concentrations were all adversely associated with the severity of the TBI, while the concentrations of IGF-1 and GH in CSF and GH in the serum were all positively related to TBI severity. Experiments in vitro and in vivo indicated that treatment with NaHS (HS donor), IGF-1, and MR-409 (GHRH agonist) showed protective effects after TBI. This study gives novel information on the functions of HS, IGF-1, and GH in TBI.

摘要

本研究旨在探讨颅脑损伤(TBI)患者中 HS、IGF-1 和 GH 的表达变化,并检测它们在 TBI 后的神经保护作用。在这项研究中,我们首先在损伤后不同时间收集 TBI 患者的脑脊液(CSF)和血浆,并评估 HS、IGF-1 和 GH 的浓度。体外研究使用划痕诱导损伤模型和细胞-细胞相互作用模型(HT22 海马神经元与 LPS 诱导的 BV2 小胶质细胞共培养)。体内研究使用小鼠控制性皮质撞击(CCI)模型。通过 CCK-8 测定法评估细胞活力。通过 qRT-PCR、ELISA 和一氧化氮产生来确定促炎细胞因子的表达。通过 Western blot 评估 CBS、CSE、IGF-1 和 GHRH 的表达。此外,通过应用改良神经严重程度评分(mNSS)、转棒试验和 Morris 水迷宫来评估 TBI 小鼠的行为功能恢复情况。我们发现,血清 HS、CSF HS 和血清 IGF-1 浓度均与 TBI 的严重程度呈负相关,而 CSF 中的 IGF-1 和 GH 浓度以及血清中的 GH 浓度均与 TBI 的严重程度呈正相关。体外和体内实验表明,NaHS(HS 供体)、IGF-1 和 MR-409(GHRH 激动剂)治疗在 TBI 后具有保护作用。本研究为 HS、IGF-1 和 GH 在 TBI 中的作用提供了新的信息。

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