The mechanism of α7nAChR mediated cholinergic anti-inflammatory pathway in the vagal nerve regulated atrial fibrillation
Shujuan Zhang1 2 3 Shudi Zhang4 Zixuan Dai1 2 3 Hongyi Zhao1 2 3 Yongsheng Qian1 2 3 Youjing Zhang1 2 3 Youcheng Wang1 2 3 Bo He 1 2 3 Yanhong Tang1 2 3 Xi Wang1 2 3 Teng Wang1 2 3 He Huang1 2 3 Qingyan Zhao1 2 3 Congxin Huang1 2 3
1.Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
2.Cardiovascular Research Institute, Wuhan University, Wuhan, Hubei 430060, China
3.Hubei Key Laboratory of Cardiology, Wuhan, Hubei 430060, China
4.Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China
Objectives: To investigate the mechanism of α7nAChR mediated cholinergic anti-inflammatory pathway in the vagal nerve regulated atrial fibrillation
Methods: Eighteen beagles were randomized into control group (n=6), LL-VNS group (n=6) and MLA group (n=6). All the beagles were subjected to rapid atrial pacing at 800 beats/min for 6 hours. The effective refractory period (ERP) of atrium and pulmonary veins and induced AF were measured hourly during non-pacing. After cessation of 3 h pacing, the control group was injected with saline into four GPs, the LL-VNS group was given LL-VNS and saline injected into four GPs, and the MLA group was injected with methyllycaconitine (an α7nAChR inhibitor) into for GPs combined with LL-VNS. Then, the level of serum tumor mecrosis factor-alpah (TNF-α), interleukin-6 (IL-6), and acetylcholine (ACh) were measured at baseine condition, 3 h and 6 h. At the end of the experiment, atrial tissues were collected and the levels of TNF-α, IL-6, ACh,α7nAChR, STAT3 and NF-κB proteins were measured.
Results: During the first 3 h pacing, the ERPs were gradually decreased while the dERPs and AF inducibility were gradually increased in all three groups, there were not significant difference in the ERPs, dERPs and AF inducibility among the three groups. During the last 3 hours, when compared with the control group and MLA group, the ERPs in the LL-VNS group wer higher, and the dERPs and AF vulnerability were significant lower at the same time points. The levels of TNF-α and IL-6 in atrial tissues were all significant decreased in LL-VNS group when compared with the control group and MLA group, and the levels of ACh in plasma and atrial tissues in the LL-VNS group and MLA group were higher than in the control group. The concentrations of α7nAChR and STAT3 proteins in RA and LA were higher in the LL-VNS group than in the control group and MLA group, and the levels of NF-κB in those tissues were lower in the LL-VNS group than in the control group and MLA group.
Conclusions: Cholinergic anti-inflammatory pathway plays an important role in low-level vagal nerve regulated AF.