Zhang Zhi-Ling, Wu Zi-Yang, Liu Feng-Yu, Zhai Suo-Di
Department of Pharmacy, Peking University Third Hospital, Beijing, China.
Key Laboratory for Neuroscience, Neuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Ministry of Education/National Health Commission, Peking University, Beijing, China.
Front Mol Neurosci. 2024 Feb 14;17:1333842. doi: 10.3389/fnmol.2024.1333842. eCollection 2024.
Oxaliplatin, a platinum-based chemotherapy drug, causes neuropathic pain, yet effective pharmacological treatments are lacking. Previously, we showed that tetrandrine (TET), with anti-inflammatory properties, reduces mechanical allodynia in nerve-injured mice. This study explores the effect of TET on oxaliplatin-induced mechanical allodynia and gene changes in mice. Male C57BL/6J mice received oxaliplatin intraperitoneally to induce mechanical allodynia. Post-treatment with TET or vehicle, the mechanical withdrawal threshold (WMT) was assessed using von Frey filaments. TET alleviated oxaliplatin-induced mechanical allodynia. RNA sequencing identified 365 differentially expressed genes (DEGs) in the Control vs. Oxaliplatin group and 229 DEGs in the Oxaliplatin vs. TET group. Pearson correlation analysis of co-regulated DEGs and inflammation-related genes (IRGs) revealed 104 co-regulated inflammation-related genes (Co-IRGs) (|cor| > 0.8, < 0.01). The top 30 genes in the PPI network were identified. Arg2, Cxcl12, H-Q6, Kdr, and Nfkbia were highlighted based on ROC analysis. Subsequently, Arg2, Cxcl12, Kdr, and Nfkbia were further verified by qRCR. Immune infiltration analysis indicated increased follicular CD4 T cell infiltration in oxaliplatin-treated mice, reduced by TET. Molecular docking showed strong binding affinity between TET and proteins encoded by Arg2, Cxcl12, Kdr, and Nfkbia. In summary, TET may alleviate oxaliplatin-induced peripheral neuropathy in clinical conditions.
奥沙利铂是一种铂类化疗药物，可导致神经性疼痛，但目前缺乏有效的药物治疗方法。此前，我们发现具有抗炎特性的粉防己碱（TET）可减轻神经损伤小鼠的机械性异常性疼痛。本研究探讨了TET对奥沙利铂诱导的小鼠机械性异常性疼痛及基因变化的影响。雄性C57BL/6J小鼠腹腔注射奥沙利铂以诱导机械性异常性疼痛。给予TET或溶剂处理后，使用von Frey细丝评估机械性撤针阈值（WMT）。TET减轻了奥沙利铂诱导的机械性异常性疼痛。RNA测序鉴定出对照组与奥沙利铂组之间有365个差异表达基因（DEG），奥沙利铂组与TET组之间有229个DEG。对共同调控的DEG和炎症相关基因（IRG）进行Pearson相关性分析，发现104个共同调控的炎症相关基因（Co-IRG）（|cor|>0.8，<0.01）。确定了PPI网络中的前30个基因。基于ROC分析，突出显示了Arg2、Cxcl12、H-Q6、Kdr和Nfkbia。随后，通过qRCR进一步验证了Arg2、Cxcl12、Kdr和Nfkbia。免疫浸润分析表明，奥沙利铂处理的小鼠中滤泡CD4 T细胞浸润增加，而TET可使其减少。分子对接显示TET与Arg2、Cxcl12、Kdr和Nfkbia编码的蛋白质之间具有很强的结合亲和力。总之，TET可能在临床情况下减轻奥沙利铂诱导的周围神经病变。
