丹参酮 IIA 对广东血管圆线虫五期幼虫排泄分泌产物处理后的小鼠星形胶质细胞的治疗作用。

The therapeutic effect of tanshinone IIA in mouse astrocytes after treatment with Angiostrongylus cantonensis fifth-stage larval excretory-secretory products.

机构信息

Department of Parasitology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Parasitology, School of Medicine, China Medical University, Taichung, 404, Taiwan.

Department of Parasitology, School of Medicine, China Medical University, Taichung, 404, Taiwan.

出版信息

J Microbiol Immunol Infect. 2023 Aug;56(4):853-862. doi: 10.1016/j.jmii.2023.04.007. Epub 2023 Apr 25.

DOI:10.1016/j.jmii.2023.04.007

PMID:37147244

Abstract

BACKGROUND

Angiostrongylus cantonensis is an important food-borne zoonotic parasite that causes eosinophilic meningitis and meningoencephalitis in humans. Excretory-secretory products (ESPs) are valuable targets for studying host-parasite relationships. ESPs are composed of a variety of molecules that are used to penetrate defensive barriers and avoid immune attack of the host. Tanshinone IIA (TSIIA) is a vasoactive cardioprotective drug that is widely used in studies evaluating potential therapeutic mechanisms. In this study, we will evaluate the therapeutic effects of TSIIA in mouse astrocytes after A. cantonensis fifth-stage larvae (L5) ESPs treatment.

METHODS

Here, we examined the therapeutic effect of TSIIA by real-time qPCR, western blotting, activity assay, and cell viability assays.

RESULTS

First, the results showed that TSIIA can elevate cell viability in astrocytes after stimulation with ESPs. On the other hand, TSIIA downregulated the expression of apoptosis-related molecules. However, the expression of molecules related to antioxidant, autophagy, and endoplasmic reticulum stress was significantly increased. The results of antioxidant activation assays showed that the activities of superoxide dismutase (SOD), glutathione S-transferase (GST), and catalase were significantly increased. Finally, we found that cell apoptosis and oxidative stress were reduced in TSIIA-treated astrocytes by immunofluorescence staining.

CONCLUSION

The findings from this study suggest that TSIIA can reduce cellular damage caused by A. cantonensis L5 ESPs in astrocytes and clarify the related molecular mechanisms.

摘要

背景

广州管圆线虫是一种重要的食源性人畜共患寄生虫，可引起人体嗜酸性脑膜炎和脑膜脑炎。排泄分泌产物（ESPs）是研究宿主-寄生虫关系的有价值的靶标。ESPs 由多种分子组成，用于穿透防御屏障并避免宿主的免疫攻击。丹参酮 IIA（TSIIA）是一种血管活性心脏保护药物，广泛用于评估潜在治疗机制的研究中。在本研究中，我们将评估 TSIIA 在 A. cantonensis 第五期幼虫（L5）ESP 处理后对小鼠星形胶质细胞的治疗效果。

方法

在这里，我们通过实时 qPCR、western blot、活性测定和细胞活力测定来检查 TSIIA 的治疗效果。

结果

首先，结果表明 TSIIA 可以提高 ESPs 刺激后星形胶质细胞的活力。另一方面，TSIIA 下调了凋亡相关分子的表达。然而，与抗氧化剂、自噬和内质网应激相关的分子表达明显增加。抗氧化激活测定的结果表明，超氧化物歧化酶（SOD）、谷胱甘肽 S-转移酶（GST）和过氧化氢酶的活性显著增加。最后，我们通过免疫荧光染色发现 TSIIA 处理的星形胶质细胞中细胞凋亡和氧化应激减少。