TaVNS reduces inflammatory responses in a L-NAME-induced rat model of pre-eclampsia

Abstract

Pre-eclampsia is characterized by an excessive maternal inflammatory response. The cholinergic antiinflammatory pathway (CAP) has been shown as the efferent arm of a vagal reflex with the potential to limit inflammatory responses. Therefore, in this study, the CAP regulation through the nervous vagal stimulation (VNS) reduced the severity of NG-nitro-L-arginine methyl ester (L-NAME)-induced pre-eclampsia was determined in a rat model. Rats were given 125 mg/kg/day of L-NAME via subcutaneous injection on gestational day (GD) 10-16. In addition, the rats were treated by active or sham electrical stimulation once a day during GD 13-19. Systolic blood pressure (SBP), urinary albumin, and pregnancy outcomes were documented for each rat. The average fetal weights and crown-rump length (CRL) as well as the placental weights of rats in both control and experimental groups were recorded onthe 13th day, 16th day and 20th day of gestation. Subsequently, placentas were collected from the rats on GD20 to measure the level of cytokines. In addition, qRT-PCR and Western blot analysis were used to detect the mRNA and protein expression of α7 nicotinic acetylcholine receptor (α7nAChR) and nuclear factor-κB (NF-κB), respectively. Immunohistochemistry assays were also carried out to determine the location and level of α7nAChR and NF-κB in placentas. CAP regulation through the transcutaneous auricular nerve stimulation alleviated the clinical symptoms in the rats after L-NAME induction, including hypertension, proteinuria, fetal growth retardation and fetal death. In addition, TaVNS also increased α7nAChR expression, reduced NF-κB p65 expression, and reversed L-NAME-induced proinflammatory cytokines in the placenta tissues, including tumor necrosis factor-alpha (TNF-α), high mobility group box 1 (HMGB-1) and interleukin-6 (IL-6). The findings of this study showed that TaVNS might be used as a promising tool to attenuate pre-eclampsia-like symptoms. In addition, the protective effect of TaVNS was associated with the improvement of α7nAChR expression and the inhibition of inflammatory reactions at the maternal-fetal interface through activating cholinergic anti-inflammation pathway.