Effect of senkyunolide I regulating the MLK3/JNK3 signaling pathway on neuronal apoptosis in sepsis-associated encephalopathy rats
10.16098/j.issn.0529-1356.2025.06.002
- VernacularTitle:洋川芎内酯I调控MLK3/JNK3信号通路对脓毒症相关性脑病大鼠神经元凋亡的影响
- Author:
Shu-Ming ZHENG
1
;
Yuan-Yuan LUO
;
Hong-Bo LI
;
Feng-Li ZHAO
;
Li-Li QIAO
Author Information
1. 广州中医药大学第一附属医院重症医学科,广州 510405
- Keywords:
Senkyunolide I;
Sepsis-associated encephalopathy;
Neuron;
Mixed lineage kinase 3/c-Jun N-terminal kinate 3 signaling pathway;
Western blotting;
Rat
- From:
Acta Anatomica Sinica
2025;56(6):644-650
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of senkyunolide I(SEN I)on neuronal apoptosis in sepsis-associated encephalopathy(SAE)rats via modulation of the mixed-lineage kinase 3(MLK3)/c-Jun N-terminal kinase 3(JNK3)signaling pathway.Methods Screening for a SAE model by monitoring neurobehavioral and electroencephalographic alterations in rats with sepsis induced by cecal ligation and puncture(CLP).Divided into normal control group,sham operation group,sepsis without encephalopathy group,SAE model group,SAE+MLK3/JNK3 signaling pathway inhibitor(URMC-099)group,SAE+low-dose SEN I group(36 mg/kg),and SAE+high-dose SEN I group(144 mg/kg),with 10 animals in each group.After 30 minutes of successful modeling,intraperitoneal injection was administered according to the group,and the administration was completed within 24 hours.HE staining was used to observe the pathological conditions of hippocampal tissue under a light microscope,transmission electron microscopy was used to observe changes in the morphology of neuronal nuclei,cytoplasm,and mitochondrial ultrastructure,TUNEL staining was used to detect hippocampal neuronal apoptosis,and Western blotting was used to detect the expression levels of p-JNK3,JNK3,p-MLK3,MLK3,and Fas ligand(Fas-L)proteins.Results Compared with the normal control group and sham surgery group,the sepsis without encephalopathy group showed no significant changes in neuronal structural morphology and neuronal apoptosis,and there were no significant differences in the expression of p-JNK3,JNK3,p-MLK3,MLK3,and Fas-L proteins(P＞0.05).However,the SAE model group had aggravated neuronal structural morphology damage,increased neuronal apoptosis rate,and increased expression level of p-JNK3,JNK3,p-MLK3,MLK3,and Fas-L proteins(P＜0.01);Compared with the SAE model group,the inhibitor URMC-099 and SEN I treatment groups showed significant improvement in neuronal structural and morphological damage,decreased neuronal apoptosis rates,and reduced p-JNK3,JNK3,p-MLK3,MLK3,and Fas-L protein expression(P＜0.01),with the high-dose SEN I group showing more significant improvement.Conclusion SEN I effectively reduces neuronal apoptosis in SAE and exerts neuroprotective effects on SAE by inhibiting the activation of the MLK3/JNK3 signaling pathway.
