桂枝茯苓汤调控METTL3/NGF通路改善硼替佐米致周围神经病变机制研究OA
Mechanism Study on the Regulation of METTL3/NGF Pathway by Guizhi Fuling Decoction(桂枝茯苓汤)in Improving Bortezomib-Induced Peripheral Neuropathy
目的 探究桂枝茯苓汤通过调控甲基转移酶样3(methyltransferase-like 3,METTL3)/神经生长因子(nerve growth factor,NGF)信号通路对硼替佐米所致周围神经病变的影响,阐明桂枝茯苓汤调节神经损伤修复的潜在干预效果.方法 8周龄雌性C57BL/6小鼠随机分成对照组、模型组(硼替佐米组)、治疗组(硼替佐米+桂枝茯苓汤),模型组与治疗组进行硼替佐米腹腔注射造模.3组进行行为学实验(热缩足潜伏期检测+冷痛觉过敏检测),神经电生理检测坐骨神经运动神经传导速度;HE染色及电镜观察坐骨神经形态;Western blot法检测坐骨神经METTL3、NGF蛋白表达水平,免疫组化法观察其在组织中的定位分布,ELISA法检测血清NGF水平.结果 与对照组相比,模型组小鼠热痛觉过敏潜伏期显著缩短(P<0.01),冷刺激抬足次数显著增加(P<0.01);坐骨神经运动神经传导速度显著降低(P<0.01);坐骨神经纤维排列紊乱、髓鞘结构受损,神经纤维密度、髓鞘形成比例及轴突直径/包含髓鞘神经纤维总直径比值(g值)均显著降低(P<0.05);坐骨神经组织中METTL3蛋白表达显著升高(P<0.01),NGF蛋白表达显著降低(P<0.01),血清NGF水平显著降低(P<0.01).与模型组相比,治疗组热缩足潜伏期延长(P<0.01),冷刺激抬足次数减少(P<0.01);坐骨神经运动神经传导速度恢复(P<0.01);坐骨神经髓鞘结构完整性改善,形态学指标升高(P<0.05);METTL3蛋白表达降低(P<0.01),NGF蛋白表达及血清NGF水平升高(P<0.01).结论 桂枝茯苓汤能够改善C57BL/6小鼠硼替佐米所致的周围神经病变,其作用机制可能与调控METTL3/NGF信号通路有关.
Objective This study aims to investigate the impact of Guizhi Fuling Decoction(桂枝茯苓汤)on bortezomib-induced peripheral neuropathy through regulating the METTL3/NGF signaling pathway,and to clarify its potential intervention role in promoting nerve injury repair.Methods Eight-week-old female C57BL/6 mice were randomly divided into control group,model group(bortezomib group)and treatment group(bortezomib+Guizhi Fuling Decoction).The model group and the treatment group were intraperitoneally injected with bortezomib.The three groups were tested for behavioral tests(thermal withdrawal latency+cold hyperalgesia).Neurophysiological examination and sciatic nerve motor nerve conduction velocity;the morphology of sciatic nerve was observed by HE staining and electron microscopy.The protein expression levels of METTL3 and NGF in sciatic nerve were detected by Western blot method.The localization and distribution of METTL3 and NGF in tissues were observed by immunohistochemistry method.The serum NGF level was detected by ELISA method.Results Compared with the control group,the latency of thermal hyperalgesia in the model group was significantly shortened(P<0.01),the number of cold stimulation foot lifts was significantly increased(P<0.01).And the nerve conduction velocity of sciatic nerve was significantly decreased(P<0.01).The arrangement of sciatic nerve fibers was disordered and the myelin sheath structure was damaged.The density of nerve fibers,the proportion of myelin sheath formation and the ratio of axon/myelin sheath thickness(g ratio)were significantly decreased(P<0.05).The expression of METTL3 protein in sciatic nerve tissue was significantly increased(P<0.01),the expression of NGF protein was significantly decreased(P<0.01),and the serum NGF level was significantly decreased(P<0.01).Compared with the model group,the thermal withdrawal latency of the treatment group was prolonged(P<0.01),the number of cold stimulation foot lifts was reduced(P<0.01).And the nerve conduction velocity of sciatic nerve was restored(P<0.01).The structural integrity of sciatic nerve myelin sheath was improved,and the morphological indexes were increased(P<0.05).METTL3 protein expression decreased(P<0.01),NGF protein expression and serum NGF level increased(P<0.01).Conclusion Guizhi Fuling Decoction can alleviate bortezomib-induced peripheral neuropathy in C57BL/6 mice,and its mechanism may be associated with the regulation of the METTL3/NGF signaling pathway.
周汝黛;崔兴
山东中医药大学,山东 济南 250013山东中医药大学第二附属医院,山东 济南 250001
医药卫生
周围神经病变桂枝茯苓汤METTL3NGF
peripheral neuropathyGuizhi Fuling Decoction(桂枝茯苓汤)METTL3NGF
《辽宁中医药大学学报》 2026 (6)
13-18,6
国家自然科学基金面上项目(82274491)山东省自然科学基金项目(ZR2024MH009)山东省自然科学基金创新发展联合基金项目(ZR2023LZL009)济南市临床医学科技创新计划项目(202225014)
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