樟芝多糖通过降低NLRP3Caspase1炎性小体表达改善帕金森小鼠神经行为学的机制研究

doi:10.12092/j.issn.1009-2501.2018.04.008

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (4): 406-412.doi: 10.12092/j.issn.1009-2501.2018.04.008

樟芝多糖通过降低NLRP3Caspase1炎性小体表达改善帕金森小鼠神经行为学的机制研究

杨毅，官俏兵，郭丽，韩晨阳

嘉兴市第二医院，嘉兴 314001，浙江

收稿日期:2017-10-19 修回日期:2017-11-29 出版日期:2018-04-26 发布日期:2018-04-13
通讯作者: 韩晨阳，男，硕士，药师，研究方向：药理学。 Tel：13736496736 E-mail：691513770@qq.com
作者简介:杨毅，男，本科，副主任药师，研究方向：药理学。 Tel：13967351048 E-mail：wasd911@126.com

Antrodia camphorata polysaccharide improved neurobehavioral function in Parkinson mice via reducing the expression of NLRP3-Caspase1 inflammatory body

YANG Yi，GUAN Qiaobin，GUO Li，HAN Chenyang

The Second Hospital of Jiaxing, Jiaxing 314001, Zhejiang, China

Received:2017-10-19 Revised:2017-11-29 Online:2018-04-26 Published:2018-04-13

摘要/Abstract

摘要：

目的:研究樟芝多糖通过降低NLRP3-Caspase1炎性小体表达改善6-OHDA构建的帕金森小鼠模型的行为学机制。方法:利用6-OHDA脑内注射构建帕金森小鼠模型，通过酪氨酸羟化酶（TH）免疫组化染色和行为学判定小鼠模型的构建成功。利用樟芝多糖进行干预，分别在干预前、干预后的第1、3、7天4个时间点进行神经行为学实验，分别采用转棒实验、爬杆实验检测小鼠自主行为能力以及协调能力，4个时间点取小鼠尾静脉外周血采用ELISA法检测外周血中Caspase1和IL-1β的表达，樟芝多糖干预第7天时待进行完行为学实验后小鼠断颈处死，取小鼠脑组织-纹状体，Western blot法检测纹状体中Caspase1、proCaspase1、NLRP3的表达，高效液相色谱检测纹状体中单胺类神经递质的表达，RT-QPCR检测Caspase1、NLRP3、IL-1β、IL-4、IL-6的mRNA表达。NISSl染色检测小鼠脑组织神经细胞凋亡情况。结果:6-OHDA脑内注射可以造成小鼠帕金森样病变，且TH蛋白表达显著下调，樟芝多糖干预后小鼠的行为学得到显著改善（P<0.05），纹状体中Caspase1、proCaspase1、NLRP3的表达显著下调，与模型小鼠相比具有统计学差异（P<0.05），且相关炎症因子Caspase1、NLRP3、IL-1β、IL-4、IL-6的mRNA表达下调（P<0.05），纹状体中单胺类神经递质表达上升（P<0.05）。结论:樟芝多糖可以通过下调NLRP3-Caspase1炎性小体表达来改善6-OHDA构建的帕金森小鼠模型行为改善，这可能是樟芝多糖治疗帕金森的机制之一。

关键词: 樟芝多糖, NLRP3-Caspase1炎性小体, 帕金森小鼠, 神经行为学

Abstract:

AIM: To study the mechanism of Antrodia camphorata polysaccharide improved neurobehavioral function in Parkinson mice via reducing the expression of NLRP3-Caspase1 inflammatory body. METHODS: The Parkinson model mice was constructed by 6-OHDA injection, and the mice model was successfully constructed by TH immunohistochemical staining and behavior intervention of Antrodia camphorata polysaccharide, neurobehavioral experiments were performed at four time points. The independent behavioral ability and coordination ability of mice were detected by rotating rod test and climbing rod test respectively. The peripheral blood of the tail vein of mice was collected at four time points and the expression of Caspase1 and IL-1β in peripheral blood was detected by ELISA method. After the 7-day intervention, the mice were killed and the brain tissue striatum was taken. Caspase1, pro Caspase1 and NLRP3 in striatum were detected by Western blot; monoamine neurotransmitters in striatum were determined by high performance liquid chromatography; mRNA expression of Caspase1, NLRP3, IL-1β, IL-4 and IL-6 were detected by RT-QPCR. NISSl staining was used to detect the apoptosis of neural cells in the brain tissue of mice. RESULTS: 6-OHDA injection could cause Parkinson like lesions in mice, and the expression of TH protein was down regulated significantly. The behavior of mice was significantly improved after Antrodia camphorata polysaccharide intervention（P<0.05）; in striatum, the expression of Caspase1, proCaspase1, NLRP3 were significantly lower than those in model mice（P<0.05）; the mRNA expression of caspase1, NLRP3, IL-1 beta, IL-4 and IL-6 was down regulated（P<0.05）; the expression of monoamine neurotransmitters increased in striatum（P<0.05）. CONCLUSION: Antrodia camphorata polysaccharide improved neurobehavioral function in Parkinson mice via reducing the expression of NLRP3-Caspase1 inflammatory body. This may be one of the mechanisms for the treatment of Parkinson with Antrodia camphorata polysaccharide.

Key words: Antrodia camphorata polysaccharide, NLRP3-Caspase1 inflammatory body, Parkinson mice, neurobehavioral

中图分类号:

R965.2

杨毅，官俏兵，郭丽，韩晨阳. 樟芝多糖通过降低NLRP3Caspase1炎性小体表达改善帕金森小鼠神经行为学的机制研究[J]. 中国临床药理学与治疗学, 2018, 23(4): 406-412.

YANG Yi，GUAN Qiaobin，GUO Li，HAN Chenyang. Antrodia camphorata polysaccharide improved neurobehavioral function in Parkinson mice via reducing the expression of NLRP3-Caspase1 inflammatory body[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(4): 406-412.

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樟芝多糖通过降低NLRP3Caspase1炎性小体表达改善帕金森小鼠神经行为学的机制研究

Antrodia camphorata polysaccharide improved neurobehavioral function in Parkinson mice via reducing the expression of NLRP3-Caspase1 inflammatory body

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