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灵芝孢子多糖改善紫杉醇诱导的肠道屏障损伤:通过逆转微管聚合抑制细胞凋亡。

Polysaccharide from spore of Ganoderma lucidum ameliorates paclitaxel-induced intestinal barrier injury: Apoptosis inhibition by reversing microtubule polymerization.

机构信息

Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, PR China; Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, Guangdong, PR China; Guangdong Yuewei Edible Fungi Technology Co. Ltd., Guangzhou, Guangdong, PR China.

Guangdong Provincial Key Laboratory of Microbial Safety and Health, State Key Laboratory of Applied Microbiology Southern China, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, Guangdong, PR China.

出版信息

Biomed Pharmacother. 2020 Oct;130:110539. doi: 10.1016/j.biopha.2020.110539. Epub 2020 Aug 5.

DOI:10.1016/j.biopha.2020.110539
PMID:32768880
Abstract

Side effects of chemotherapy are burning questions for physicians and patients involved in cancers. Ganoderma lucidum is a widely consumed traditional Chinese medicine and edible mushroom with multiple functional properties. The present study aims to investigate the potential of polysaccharides from spore of G. lucidum (SGP) on small intestinal barrier function recovery against paclitaxel (PTX) challenge in a breast cancer mice model and IEC-6 cell line. The 4T1 tumor-bearing mice were treated with PTX together with four-week daily oral administration of SGP. Results indicated that combination of PTX and SGP reversed body weight lost and remolded the histology of small intestine, accompanied with promoted proliferation but suppressed apoptosis in intestinal cells. Intestinal barrier function was enhanced by the combination as indicated by reduced endotoxemia and the up-regulation of tight junction proteins, including Zonula occludens-1 (ZO-1), E-cadherin, β-catenin and Occludin. The protection of SGP was further confirmed in IEC-6 cells affected by PTX in vitro. The combination treatment prevented PTX-induced apoptosis in IEC-6 by inhibiting microtubule polymerization, and the aforementioned tight junction proteins were also upregulated. These findings suggest a promising protective effect of SGP against small intestinal barrier injury caused by PTX, highlighting its clinical implication against the chemotherapy side effects.

摘要

化疗的副作用是参与癌症治疗的医生和患者关注的热点问题。灵芝是一种广泛食用的中药和食用蘑菇,具有多种功能特性。本研究旨在探讨灵芝孢子多糖(SGP)对紫杉醇(PTX)诱导的乳腺癌小鼠模型和 IEC-6 细胞系中小肠屏障功能恢复的潜在作用。荷 4T1 肿瘤的小鼠接受 PTX 治疗,并同时给予为期四周的每日口服 SGP。结果表明,PTX 与 SGP 的联合使用逆转了体重减轻,并重塑了小肠的组织学形态,同时促进了肠道细胞的增殖,抑制了细胞凋亡。联合用药增强了肠道屏障功能,表现为内毒素血症降低,以及紧密连接蛋白(包括闭锁蛋白-1[ZO-1]、E-钙黏蛋白、β-连环蛋白和闭合蛋白)的上调。体外实验中,SGP 对受 PTX 影响的 IEC-6 细胞也有保护作用。联合治疗通过抑制微管聚合来防止 PTX 诱导的 IEC-6 细胞凋亡,上述紧密连接蛋白也上调。这些发现表明 SGP 对 PTX 引起的小肠屏障损伤具有有前景的保护作用,突出了其在对抗化疗副作用方面的临床意义。

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