电针对帕金森病小鼠肠道硫氧还蛋白相互作用蛋白/核苷酸结合寡聚化结构域样受体3信号通路的影响

Effects of electroacupuncture on the intestinal thioredoxin interaction protein/Nod-like receptor 3 signaling pathway in mice with Parkinson's disease.

作者信息

Wang Yao, Wang Yan-Chun, Ma Jun, Li Ya-Nan, Zhang Xiao-Lei, Hu Meng-Ni, Qi Ling, Guo Lei, Rong Zhen, Guan Qing-Ya

机构信息

College of Physical Education and Health, Hubei University of Chinese Medicine, Wuhan 430061, China.

Clinical College of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan 430061.

出版信息

Zhen Ci Yan Jiu. 2023 Oct 25;48(10):1041-1047. doi: 10.13702/j.1000-0607.20220554.

DOI:10.13702/j.1000-0607.20220554

PMID:37879955

Abstract

OBJECTIVES

To observe the effects of electroacupuncture (EA) at "Fengfu" (GV16), "Taichong" (LR3) and "Zusanli" (ST36) on α-synuclein (α-syn), Occludin, Claudin-1, thioredoxin interaction protein (TXNIP) and Nod-like receptor 3 (NLRP3) in Parkinson's disease (PD) mice, so as to investigate the mechanisms of EA on intestinal barrier function and inflammation in PD mice.

METHODS

Thirty six C57BL/6 mice were randomly divided into control, model and EA groups, with 12 mice in each group. PD mice model was induced by rotenone intragastric administration for 28 days. Mice in the EA group were treated with EA (2 Hz, 1 mA) at GV16, LR3 and ST36 for 30 min, once a day for 14 days. The behavioral scores were observed. The total distance of autonomic movement was measured by open field test. The expression level of α-syn in substantia nigra and colon tissue was determined by immunohistochemistry. The colonic morphology and goblet cell distribution were observed by Alcian blue staining. The expression levels of Occludin, Claudin-1, TXNIP and NLRP3 mRNA in colon tissue were detected by real-time fluorescence quantitative PCR.

RESULTS

Compared with the control group, the behavioral scores of rats were increased (<0.01)；the total distance of autonomous movement was decreased (<0.01)；the positive expression level of α-syn in the substantia nigra and colon was increased (<0.01)；the goblet cells and crypts in colon tissue were reduced, and the muscular layer was thinner；the expression levels of Occludin and Claudin-1 mRNAs in colon tissue were decreased (<0.01) while TXNIP and NLRP3 mRNAs were increased (<0.01) in the model group. Compared with the model group, the surface villi of colon tissue was more complete, the goblet cells and crypts were increased, and the muscular layer was thickened；the other indexes were reversed (<0.01, <0.05) in the EA group.

CONCLUSIONS

EA at GV16, LR3 and ST36 can reduce the abnormal accumulation of α-syn in the substania nigra and colon tissue of PD mice, alleviate the damage of intestinal barrier, regulate TXNIP/NLRP3 signaling pathway, so as to delay the occurrence and development of PD.

摘要

目的

观察电针“风府”（GV16）、“太冲”（LR3）和“足三里”（ST36）对帕金森病（PD）小鼠α-突触核蛋白（α-syn）、闭合蛋白、紧密连接蛋白-1、硫氧还蛋白相互作用蛋白（TXNIP）和NOD样受体3（NLRP3）的影响，以探讨电针对PD小鼠肠道屏障功能及炎症的作用机制。

方法

将36只C57BL/6小鼠随机分为对照组、模型组和电针组，每组12只。采用鱼藤酮灌胃28天诱导建立PD小鼠模型。电针组小鼠于GV16、LR3和ST36穴给予电针治疗（2Hz，1mA），每次30分钟，每日1次，共14天。观察小鼠行为学评分，采用旷场试验测定自主活动总距离。采用免疫组织化学法检测黑质和结肠组织中α-syn的表达水平。采用阿尔新蓝染色观察结肠形态及杯状细胞分布。采用实时荧光定量PCR检测结肠组织中闭合蛋白、紧密连接蛋白-1、TXNIP和NLRP3 mRNA的表达水平。

结果

与对照组比较，模型组小鼠行为学评分升高（<0.01），自主活动总距离缩短（<0.01），黑质和结肠组织中α-syn阳性表达水平升高（<0.01），结肠组织杯状细胞和隐窝减少，肌层变薄；结肠组织中闭合蛋白和紧密连接蛋白-1 mRNA表达水平降低（<0.01），TXNIP和NLRP3 mRNA表达水平升高（<0.01）。与模型组比较，电针组结肠组织表面绒毛更完整，杯状细胞和隐窝增多，肌层增厚；其余指标均得到改善（<0.01，<0.05）。