Effect And Mechanism Of Stimulating Vagus Nerve On Rats With Collagen Induced Arthritis

Objective: To establish a chronic vagus nerve stimulated (VNS) model of collagen induced arthritis(CIA) in rats and investigate the effect and mechanism of stimulating vagus nerve on CIA rats. Explore a new treat way for CIA and other autoimmune disease.Methods: Thirty healthy Wistar rats (male, 4 to 5 weeks old, 150±10g weight) were divided into experimental model group and normal group randomly. An experimental model of Wistar rats was reproduced by intradermal injection multipoint ofⅡtype collagen. After a week, the model rats were boostly injected in the same way. The CIA model rats were divided into two groups: vagus nerve stimulated (VNS) group and sham operated group. Rats in group VNS were stimulated at the left cervical vagus nerves for 30 minutes a day with constant square wave, pulse current with intra train of 16Hz, pulse duration of 1.0ms, train duration of 10s, interstimulus interval of 1.5min and intensities of 3.0mA for 4 weeks.We examined the relative indexes as follow:1. Arthritis index;2. After 4 weeks treatment, the synovium of ankle joint were stained with H-E to observe the histopathologic changes ;3. Detecting the expression CD71(stand for activation of CD4+T lymphocytes), nicotinic acetylcholine receptorα7(nAChRα7) and choline acetyltransferase (ChAT) by flow cytometry in peripheral blood CD4+T lymphocytes;4. Inspecting the expression of nAChRα7, ChAT, CD68(macrophage mark ) in synovium tissue by immunohistochemical method ; 5. Detecting the expression of nAChRα7 and ChAT mRNA by RT-PCR method;Results:1 The arthritis index showed significant difference in group VNS compared to the sham operated group (p<0.01);2 The histopathology of synovium ankle joint of in group VNS was parrently different with the sham operated group (p<0.01);3 After 1 weeks'treatment,the expression of nAChRα7 and ChAT in CD4+ T lymphocyte in group VNS were significantly higher than the sham operated group; after2 weeks'treatment, the activation of CD4+ T lymphocyte and the expression of nAChRα7 and ChAT in CD4+ T lymphocyte of group VNS were much lower than the sham operated group(p<0.01);4 The expression of nAChRα7 and ChAT in synovium of VNS group was higher than the sham operated group detected by immunohistochemical method, but the expression of CD68 was lower than the sham operated group (p<0.01);5 The level of nAChRα7 mRNA,ChAT mRNA in synovium of group VNS was much higher than the sham operated group(p<0.01);Conclusion:Vagus nerve stimulation can up-regulate the expression of nAChRα7 at the surface of immune cells, activate the cholinergic system in immune system, which perform a local and constant immune regulation to reduce the inflammation and treat CIA. The research maybe open a new way for treatment of RA.