期刊
FRONTIERS IN PHARMACOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.793374
关键词
alpha 7nAChR; 6-hydroxydopamine; gastric inflammation; macrophage; Parkinson's disease
资金
- Beijing Municipal Natural Science Foundation of China [7182014, 5172006]
- National Natural Science Foundation of China [32171121, 31871159]
- Key Scientific and Technological Project of Henan Province [202102310348]
The study demonstrates that using α7nAChR agonists can alleviate inflammation and gastric dysmotility in PD rats by inhibiting NF-kappa B activation and monocyte chemotactic protein-1 expression.
The cholinergic anti-inflammatory pathway (CAIP) has been proposed to regulate gastrointestinal inflammation via acetylcholine released from the vagus nerve activating alpha 7 nicotinic receptor (alpha 7nAChR) on macrophages. Parkinson's disease (PD) patients and PD rats with substantia nigra (SN) lesions exhibit gastroparesis and a decayed vagal pathway. To investigate whether activating alpha 7nAChR could ameliorate inflammation and gastric dysmotility in PD rats, ELISA, western blot analysis, and real-time PCR were used to detect gastric inflammation. In vitro and in vivo gastric motility was investigated. Proinflammatory mediator levels and macrophage numbers were increased in the gastric muscularis of PD rats. alpha 7nAChR was located on the gastric muscular macrophages of PD rats. The alpha 7nAChR agonists PNU-282987 and GTS-21 decreased nuclear factor kappa B (NF-kappa B) activation and monocyte chemotactic protein-1 mRNA expression in the ex vivo gastric muscularis of PD rats, and these effects were abolished by an alpha 7nAChR antagonist. After treatment with PNU-282987 in vivo, the PD rats showed decreased NF-kappa B activation, inflammatory mediator production, and contractile protein expression and improved gastric motility. The present study reveals that alpha 7nAChR is involved in the development of gastroparesis in PD rats and provides novel insight for the treatment of gastric dysmotility in PD patients.
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