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醒脑灌肠液对脓毒症小鼠脑损伤的保护作用及机制研究

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目的 探寻醒脑灌肠液对脓毒症小鼠脑损伤的保护作用及其可能机制.方法 50只小鼠随机分为空白组、模型组、阻滞剂组和醒脑灌肠液低剂量组、高剂量组.采用腹腔注射LPS构建脓毒症模型.造模后,阻滞剂组予以Nec-1s 2 mg/kg腹腔注射7 d,每天1次;醒脑灌肠液低剂量组、高剂量组分别给予醒脑灌肠液2.5、5.0g/kg连续灌肠给药7 d,每天1次.对各组小鼠行神经学反射评分,收集血清及脑组织,检测脑组织病理学变化、脑损伤标志物(NSE、S100β)和炎症因子[肿瘤坏死因子-o(TNF-α)、白细胞介素-6(IL-6)]水平、坏死性凋亡信号通路蛋白表达情况.结果 与空白组比较,模型组小鼠神经学反射评分降低,脑组织病理学改变严重,NSE、S100β、血清及脑组织中TNF-α、IL-6水平上升,脑组织p-RIPK1、p-RIPK3、p-MLKL、NF-κB P65蛋白的表达增加(P<0.05);与模型组比较,阻滞剂组、醒脑灌肠液高剂量组小鼠的神经学反射评分提高,脑组织病理学改变较轻,NSE、S100β、血清及脑组织中TNF-α、IL-6水平下降,脑组织p-RIPK1、p-RIPK3、p-MLKL、NF-κB P65蛋白的表达下调(P<0.05);与醒脑灌肠液低剂量组比较,高剂量组小鼠的神经学反射评分提高,脑组织病理学改变减轻,NSE、S100β、血清及脑组织中TNF-α、IL-6水平下降,脑组织p-RIPK1、p-RIPK3、p-MLKL、NF-κB P65蛋白的表达量下调(P<0.05).结论 醒脑灌肠液对脓毒症小鼠的脑损伤有保护作用,疗效与剂量呈正相关,其作用机制可能与其抑制RIPK1/RIPK3/MLKL信号通路激活,抑制NF-κB P65的活化,抑制炎症反应有关.
The Protective Effect and Mechanism of Xingnao Enema Fluid on Brain Injury in Mice with Sepsis
Objective:To investigate the protective effect and possible mechanism of Xingnao Enema Fluid on brain injury in mice with sepsis.Methods:50 mice were randomly divided into blank group,model group,blocker group,Xingnao Enema Fluid low and high dose group.Mice were constructed by intraperitoneal injection of LPS to construct a sepsis model.After modeling,the blocker group was given the blocker Nec-1s 2 mg/kg intraperitone-ally for 7 days,once a day;the low and high dose groups of Xingnao Enema Fluid were given 2.5 g/kg and 5.0 g/kg continuous enema for 7 days,once a day;after the intervention,the neurological reflex score was performed,se-rum and brain tissues were collected,and the brain histopathological changes,brain injury markers(NSE,S100β)and inflammatory factors(TNF-α,IL-6)levels,and necroptosis signaling pathway protein expression were ana-lyzed in each group.Results:Compared with the blank group,the neurological reflex score of the model group de-creased,the brain histopathological changes were severe,the levels of brain injury markers(NSE.S100β),serum and brain inflammatory factors(TNF-α,IL-6)increased,and the expression of p-RIPK1,p-RIPK3,p-MLKL and NF-κB P65 proteins in brain tissue increased(P<0.05).Compared with the model group,the pathological chang-es of brain tissue in high-dose Xingnao Enema Fluid group and blocker group were reduced,the levels of brain in-jury markers(NSE,S100β),serum and brain inflammatory factors(TNF-α,IL-6)decreased,and the expression of p-RIPK1,p-RIPK3,p-MLKL and NF-κB P65 proteins in brain tissue was down-regulated(P<0.05).Compared with the low-dose Xingnao Enema Fluid group,the neurological reflex score of the high-dose group was increased,the brain histopathological changes were reduced,the levels of brain injury markers(NSE,S100β),serum and brain inflammatory factors(TNF-α,IL-6)decreased,and the expression of p-RIPK1,p-RIPK3,p-MLKL and NF-κB P65 proteins in brain tissue was down-regulated(P<0.05).Conclusion:Xingnao Enema Fluid has a protec-tive effect on brain injury in mice with sepsis,and its effect is positively correlated with the dose of Xingnao Ene-ma Fluid,and its mechanism of action may be related to its inhibition of RIPK1/RIPK3/MLKL signaling pathway activation,inhibition of NF-κB activation,and inhibition of inflammatory response.

SepsisBrain injuryXingnao Enema FluidNecroptosisMice

邓健超、王帝、王萌、李华

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河南中医药大学,河南郑州 450002

脓毒症 脑损伤 醒脑灌肠液 坏死性凋亡 小鼠

2024

中国中医急症
中华中医药学会

中国中医急症

CSTPCD
影响因子:1.144
ISSN:1004-745X
年,卷(期):2024.33(9)