桂枝茯苓胶囊调控mTOR自噬通路改善硼替佐米相关周围神经病变的研究

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中文摘要：目的借助网络药理学及体内外实验探讨桂枝茯苓胶囊(GZFL)干预硼替佐米(Bortezomib，BTZ)导致周围神经病变(Bortezomib-induced peripheral neuropathy，BiPN)的作用成分与机制。方法通过药物-疾病-靶点网络图、交集靶点PPI寻找桂枝茯苓胶囊的有效成分与靶点，并进行GO分析与KEGG通路分析。PC12神经细胞随机分为对照组、模型组及治疗组，免疫荧光检测LC3阳性细胞，Western Blot检测自噬蛋白表达水平。C57BL/6小鼠随机分成对照组、模型组及治疗组，采用BTZ腹腔注射法造模。对各组小鼠进行行为学、组织学检测，应用免疫组化检测小鼠坐骨神经LC3 Ⅱ/Ⅰ、Beclin 1、P62、mTOR、NGF表达水平。结果 ①网络药理学分析得到GZFL治疗BiPN的34个有效成分及107个靶点，显著富集于mTOR、MAPK等自噬相关通路;②体外实验表明，GZFL能够促进PC12神经细胞自噬水平，减少mTOR表达;③体内实验显示，与模型组相比，治疗组小鼠LC3 Ⅱ/Ⅰ、Beclin1、NGF表达水平显著增高，P62、mTOR水平显著下降。结论桂枝茯苓胶囊通过抑制mTOR相关通路促进自噬，改善多发性骨髓瘤硼替佐米治疗导致的周围神经病变，为中医药治疗化疗相关并发症提供新的思路。

外文标题：Mechanism research of Guizhifuling capsule on improving bortezomib-induced periph-eral neuropathy by interfering autophagy

外文摘要：Objective To investigate the components and mechanism of Guizhi Fuling Capsule(GZFL)on peripheral neuropathy(BiPN)induced by bortezomib(BTZ)by network pharmacology and in vitro and in vivo experiments.Methods The effective components and targets of Guizhi Fuling Capsule were found by drug-disease-target network diagram and intersection target PPI,and GO analysis and KEGG pathway analysis were carried out.PC12 cells were randomly divided into blank,BTZ,and GZ-FL groups.LC3 positive cells were detected by immunofluorescence,and the expression level of autophagy protein was detected by Western Blot.C57 BL/6 mice were randomly divided into normal control,model,and GZFL groups.Behavioral and histolog-ical tests were performed on each group of mice.Immunohistochemistry was used to detect the expression levels of LC3Ⅱ/Ⅰ,Bec-lin 1,P62,mTOR and NGF in the sciatic nerve of mice.Results 34 effective components and 107 targets of GZFL in the treat-ment of BiPN were obtained by network pharmacology analysis,which were significantly enriched in autophagy-related pathways such as mTOR and MAPK.In vitro experiments showed that GZFL could promote the level of autophagy and reduce the expression of mTOR in PC12 cells.In vivo experiments showed that compared with the model group,the expression levels of LC3B,Beclin 1 in the GZFL group were significantly increased,and the levels of P62 and mTOR were significantly decreased.Conclusion GuizhiFuling Capsule promotes autophagy by inhibiting mTOR-related pathways,improves peripheral neuropathy caused by bortezomib treatment of multiple myeloma,and provides new ideas for the treatment of chemotherapy-related complica-tions with traditional Chinese medicine.

外文关键词：

Guizhi Fuling capsuleBortezomibPeripheral neuropathyAutophagymTOR

作者：

付佳琪、蔡治国、孙润洁、崔兴

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作者单位：

山东中医药大学中医学院,山东济南 250013

山东中医药大学附属医院,山东济南 250013

山东中医药大学第二附属医院,山东济南 250001

关键词：

桂枝茯苓胶囊硼替佐米周围神经病变自噬 mTOR

基金：

国家自然科学基金面上项目国家自然科学基金面上项目泰山学者青年专家人才项目山东省重点研发计划(公益类)山东省自然科学基金山东省济南市临床医学科技创新计划山东省中医药科技发展计划面上项目

项目编号：

8207434882274491tsqn2018121452019GSF108162ZR2020MH388202225014M-2022158

出版年：

2024

DOI：

10.3969/j.issn.1008-0805.2024.05.58

时珍国医国药

时珍国医国药杂志社

时珍国医国药

北大核心

影响因子：0.887

ISSN：1008-0805

年,卷(期)：2024.35(5)