瑞马唑仑对颅脑损伤大鼠脑组织损伤及TLR4/MyD88/NF-κB通路的影响

doi:10.3969/j.issn.1006-6233.2024.02.01

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摘要 目的: 探讨瑞马唑仑(Rem)对颅脑损伤(BI)大鼠脑组织损伤及Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核因子-κB(NF-κB)通路的影响。方法: 构建BI大鼠模型;将所有大鼠分为对照组(Control组)、颅脑损伤组(BI组)、瑞马唑仑低、中、高剂量组(Rem-L、Rem-M、Rem-H组)、瑞马唑仑高剂量+TLR4激活剂LPS组(Rem-H+LPS组);检测大鼠脑组织含水量;ELISA检测大鼠脑组织中的炎症因子肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平;HE染色观察大鼠脑组织的形态学变化;TUNEL法检测脑组织神经元凋亡情况;Western blot法检测大鼠脑组织TLR4、MyD88、NF-κB、p-NF-κB p65、Bax、Bcl-2蛋白表达情况。结果: 与Control组相比,BI组大鼠脑组织神经元变性坏死,数量减少,体积缩小,损伤严重,神经功能评分、脑组织含水量、神经元凋亡率和TNF-α、IL-1β、IL-6水平及Bax、TLR4、MyD88、NF-κB、p-NF-κB p65表达升高,Bcl-2表达降低(P<0.05);与BI组相比,Rem-L、Rem-M、Rem-H组大鼠脑组织神经元细胞损伤逐渐减少,细胞结构相对较清晰,神经功能评分、脑组织含水量、神经元凋亡率和TNF-α、IL-1β、IL-6水平及Bax、TLR4、MyD88、NF-κB、p-NF-κB p65表达依次降低,Bcl-2表达依次升高(P<0.05);与Rem-H组相比,Rem-H+LPS组大鼠脑组织损伤加重,神经功能评分、脑组织含水量、神经元凋亡率和TNF-α、IL-1β、IL-6水平及Bax、TLR4、MyD88、NF-κB、p-NF-κB p65表达升高,Bcl-2表达降低(P<0.05)。结论: 瑞马唑仑可以通过抑制TLR4/MyD88/NF-κB通路改善颅脑损伤大鼠的脑组织损伤。

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关键词 ：瑞马唑仑, 颅脑损伤, Toll样受体4/髓样分化因子88/核因子-κB通路

Abstract：Objective: To investigate the effects of Remimazolam on brain tissue injury and the Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) pathway in rats with traumatic brain injury (BI). Methods: BI rat model was constructed; All rats were grouped into Control group, brain injury group (BI group), low, medium and high dose Remimazolam groups (Rem-L, Rem-M, Rem-H groups), and high dose Remimazolam+TLR4 activator LPS group of (Rem-H+LPS group); the brain tissue water content was detected; ELISA was applied to detect the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in rat brain tissue; HE staining was applied to observe the morphological changes of brain tissue; TUNEL method was applied to detect neuronal apoptosis in brain tissue; Western blot method was applied to detect the expression of TLR4, MyD88, NF-κB, p-NF-κB p65, Bax, and Bcl-2 proteins in brain tissue. Results: Compared with Control group, brain neurons in BI group were degenerated and necrotic, the number of neurons decreased, the volume decreased, and the injury was serious. Neural function score, brain tissue water content, neuronal apoptosis rate, levels of TNF-α, IL-1β, IL-6 and expressions of Bax, TLR4, MyD88, NF-κB, p-NF-κB p65 were increased. Bcl-2 expression decreased (P<0.05); Compared with BI group, the neuronal cell damage in brain tissue of rats in Rem-L, Rem-M and Rem-H groups was gradually reduced, and the cell structure was relatively clear. The neural function score, brain tissue water content, neuronal apoptosis rate, TNF-α, IL-1β, IL-6 levels and the expressions of Bax, TLR4, MyD88, NF-κB, p-NF-κB p65 were decreased successively, while the expression of Bcl-2 was increased successively (P<0.05); Compared with the Rem-H group, the brain tissue injury of the rats in the Rem-H+LPS group was aggravated, the neural function score, brain tissue water content, neuronal apoptosis rate, the levels of TNF-α, IL-1β, IL-6 and the expressions of Bax, TLR4, MyD88, NF-κB, p-NF-κB p65 were increased, and the expression of Bcl-2 was decreased (P<0.05). Conclusion: Remimazolam can improve brain tissue injury in rats with traumatic brain injury by inhibiting the TLR4/MyD88/NF-κB pathway.

Key words： Remimazolam Traumatic brain injury Toll like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway

基金资助:河北省保定市科技计划项目,(编号:2341ZF215)

通讯作者: 范艳霞

引用本文:

王东亚, 乔丹, 陈炜佳, 张懿兰, 范艳霞, 刘博峰. 瑞马唑仑对颅脑损伤大鼠脑组织损伤及TLR4/MyD88/NF-κB通路的影响[J]. 河北医学, 2024, 30(2): 177-182.
WANG Dongya, QIAO Dan, CHEN Weijia, et al. Effects of Remimazolam on Brain Tissue Injury and TLR4/MyD88/NF-κB Pathway in Rats with Traumatic Brain Injury. HeBei Med, 2024, 30(2): 177-182.

链接本文:

http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2024.02.01 或 http://www.hbyxzzs.cn/CN/Y2024/V30/I2/177

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