天麻素通过 PKA/CREB/Bcl2 轴防止创伤性脑损伤大鼠的神经元凋亡和改善神经功能缺损。

Gastrodin Prevents Neuronal Apoptosis and Improves Neurological Deficits in Traumatic Brain Injury Rats through PKA/CREB/Bcl2 Axis.

机构信息

Department of Neurosurgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, 310030 Hangzhou, Zhejiang, China.

The Fourth Clinical Medical College, Zhejiang Chinese Medical University, 310053 Hangzhou, Zhejiang, China.

出版信息

Front Biosci (Landmark Ed). 2023 May 18;28(5):93. doi: 10.31083/j.fbl2805093.

DOI:10.31083/j.fbl2805093

PMID:37258463

Abstract

BACKGROUND

Gastrodin (Gas) exhibits anti-inflammatory properties against diseases associated with the central nervous system (CNS). This study aimed to investigate the potential neuroprotective role of Gas in traumatic brain injury (TBI).

METHODS

A rat TBI model was established in male adult Sprague-Dawley (SD) rats by controlled cortical impingement (CCI), and lipopolysaccharide (LPS) was applied to induce the activation of BV2 microglia and HT22 hippocampal neurons. Neurological deficits, motor function and brain water content were evaluated in TBI rats. TUNEL and Nissl's staining were applied to measure neuronal degeneration and apoptosis. Microglial activation, the mRNA and protein profiles of pro-inflammatory cytokines were tested by immunohistochemistry (IHC), quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively.

RESULTS

Gas significantly reduced neurological deficits, cerebral edema, and neuronal apoptosis and improved motor function in TBI mice. In addition, Gas inactivated microglia and blocked the production of pro-inflammatory cytokines on the damaged side of the TBI rat brain. , Gas attenuated BV2 microglia inflammation and reduced HT22 hippocampal neuronal apoptosis. On the other hand, Gas activated the PKA/CREB/BDNF pathway both and .

CONCLUSIONS

Gas blocks microglial activation-mediated inflammation through the PKA/CREB/BDNF pathway, thereby improving neurobehavioral function after TBI, which provides a potential therapeutic benefit for treating TBI.

摘要

背景

天麻素（Gas）具有抗炎特性，可对抗与中枢神经系统（CNS）相关的疾病。本研究旨在探讨 Gas 在创伤性脑损伤（TBI）中的潜在神经保护作用。

方法

雄性成年 Sprague-Dawley（SD）大鼠采用皮质撞击伤（CCI）建立 TBI 模型，并应用脂多糖（LPS）诱导 BV2 小胶质细胞和 HT22 海马神经元的激活。TBI 大鼠评估神经功能缺损、运动功能和脑水含量。通过 TUNEL 和尼氏染色测量神经元变性和细胞凋亡。通过免疫组化（IHC）、定量逆转录-聚合酶链反应（qRT-PCR）和酶联免疫吸附试验（ELISA）分别检测小胶质细胞激活、促炎细胞因子的 mRNA 和蛋白谱。

结果

Gas 可显著减轻 TBI 小鼠的神经功能缺损、脑水肿和神经元凋亡，并改善其运动功能。此外，Gas 可使 TBI 大鼠损伤侧大脑中的小胶质细胞失活并阻断促炎细胞因子的产生。Gas 减轻了 BV2 小胶质细胞的炎症并减少了 HT22 海马神经元的凋亡。另一方面，Gas 通过 PKA/CREB/BDNF 通路激活了。