Mechanism of ligustrazine in improving chemotherapy-induced neuropathic pain based on the Ras homolog gene family member A/p38 mitogen-activated protein kinase signaling pathway
- VernacularTitle:基于Ras同源基因家族成员A/p38丝裂原活化蛋白激酶信号通路探讨川芎素改善化疗所致神经病理性疼痛的作用机制
- Author:
Ying LING
1
;
Nan DING
Author Information
- Keywords: ligustrazine; Ras homolog gene family member A; p38 mitogen-activated protein kinase; chemotherapy; neuropathic pain; apoptosis; autophagy; malondialdehyde
- From: Journal of Clinical Medicine in Practice 2025;29(8):70-77
- CountryChina
- Language:Chinese
- Abstract: Objective To explore the mechanism of ligustrazine(LC)in improving chemothera-py-induced neuropathic pain(CINP)by regulating the Ras homolog gene family member A(RhoA)/p38 mitogen-activated protein kinase(p38MAPK)signaling pathway.Methods Sixty SD rats were randomly divided into five groups:control group(Con group),model group(Model group),low-dose LC group(L-LC group),high-dose LC group(H-LC group),and high-dose LC+lysophosphatidic acid group(H-LC+LPA group),with 12 rats in each group.Pain behavioral tests were performed on the rats.Neuronal lesions were observed using hematoxylin-eosin staining.The levels of reactive oxy-gen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β),and interleukin-10(IL-10)were detected using enzyme-linked immunosorbent assay(ELISA).The expression levels of apoptosis,autophagy,and RhoA/p38MAPK signaling pathway-related proteins were detected using western blot.The apoptosis level in the spinal dorsal horn tissue was detected using TUNEL.Results On 3,5,and 7 d after surgery,the me-chanical withdrawal threshold(MWT)and thermal withdrawal latency(TWT)in the Model group were lower than those in the Con group.The MWT and TWT in the L-LC group and H-LC group were higher than those in the Model group,and the MWT and TWT in the H-LC group were higher than those in the L-LC group(P＜0.05).The MWT and TWT in the H-LC+LPA group were lower than those in the H-LC group(P＜0.05).Compared with the Con group,the expression levels of IL-10,SOD,B-cell lymphoma-2(Bcl-2),autophagy-related protein(Beclin-1),BNIP protein,and LC3-Ⅱ/LC3-Ⅰ were decreased in the Model group,while the levels of TNF-α,IL-1β,ROS,MDA,caspase-1,Bax,RhoA,phosphorylated p38 mitogen-activated protein kinase(P-p38MAPK)/p38MAPK protein expression,and apoptosis rate were increased(P＜0.05).Compared with the Model group,the expression levels of IL-10,SOD,Bcl-2,Beclin-1,BNIP protein,and LC3-Ⅱ/LC3-Ⅰ were in-creased in the L-LC group and H-LC group,while the levels of TNF-α,IL-1β,ROS,MDA,caspase-1,Bax,RhoA,P-p38MAPK/p38MAPK protein expression,and apoptosis rate were de-creased in a dose-dependent manner(P＜0.05).Compared with the H-LC group,the MWT,TWT,expression levels of IL-10,SOD,Bcl-2,Beclin-1,BNIP protein,and LC3-Ⅱ/LC3-Ⅰ were significantly decreased in the H-LC+LPA group,while the levels of TNF-α,IL-1β,ROS,MDA,caspase-1,Bax,RhoA,P-p38MAPK/p38MAPK protein expression,and apoptosis rate were in-creased(P＜0.05).Conclusion LC may alleviate the neuropathic disease symptoms in CINP rats by inhibiting the RhoA/p38MAPK signaling pathway,thereby inhibiting oxidative stress,neuroin-flammation,and apoptosis,and promoting autophagy.
