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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

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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。
Effects of Remimazolam on Brain Tissue Injury and TLR4/MyD88/NF-κB Pathway in Rats with Traumatic Brain Injury
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 vol-ume decreased,and the injury was serious.Neural function score,brain tissue water content,neuronal apop-tosis 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 suc-cessively,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 in-hibiting the TLR4/MyD88/NF-κB pathway.

RemimazolamTraumatic brain injuryToll like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway

王东亚、乔丹、陈炜佳、张懿兰、范艳霞、刘博峰

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河北省保定市第二医院, 河北 保定 071000

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

河北省保定市科技计划项目

2341ZF215

2024

河北医学
河北省医学会

河北医学

CSTPCD
影响因子:1.915
ISSN:1006-6233
年,卷(期):2024.30(2)
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