Objective: To observe the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the improvement of depressive-like behavior and the splenic α7 nicotinic acetylcholine receptor (α7nAchR) / Janus kinase 2 (JAK2 / signal transducer and activator of transcription 3 (STAT3) signaling pathway in lipopolysaccharide (LPS)-induced depressive-like behavior rats, so as to investigate the antidepressant mechanism of taVNS.
Methods: SD rats were randomly divided into SD control group, SD model group and SD taVNS group, and α7nAchR knockout rats were also randomly divided into α7 control group, α7 model group and α7 taVNS group, with 6 rats in each group. Rat model of depressive-like behavior was established by intraperitoneal injection of LPS (1 mg/kg). Rats in both SD taVNS and α7 taVNS groups received taVNS intervention once a day (2 Hz/15 Hz, 2 mA, 30 min) from 7 days before LPS injection to 2 days after LPS injection, respectively. The mean speed, activity time and side immobility time in the open field test were recorded after taVNS. The contents of interleukin 10 (IL-10) and chemokine (C-X-C motif) ligand 1 (CXCL1) in serum were detected by electrochemiluminescence multifactorial method. The splenic phosphorylated (p)-JAK2 and p-STAT3 protein expressions were detected by Western blot.
Results: Compared with their respective control groups, the mean speed and active time were reduced (P<0.01, P<0.05, P<0.001) and the side immobility time was increased (P<0.001) in the open field test, serum IL-10 and CXCL1 levels were up-regulated (P<0.01, P<0.05, P<0.001), and splenic p-JAK2 protein expressions were down-regulated (P<0.05, P<0.01) in SD and α7nAchR knockout rats, and splenic p-STAT3 protein expression were down-regulated (P<0.05) in SD rats after LPS injection. Following taVNS intervention and in comparison with the model group , the mean speed and active time were increased (P<0.01) and the side immobility time was decreased (P<0.001) in the open field test, serum IL-10 and CXCL1 levels down-regulated (P<0.05), while splenic p-JAK2 and p-STAT3 protein expressions were up-regulated (P<0.01, P<0.001) in the SD taVNS group rather than in the α7 taVNS group. Compared with SD taVNS group, the α7 taVNS group showed increased (P<0.001, P<0.05) side immobility time in the open field test and serum IL-10, decreased splenic p-JAK2 and p-STAT3 protein expressions (P<0.01, P<0.05).
Conclusion: taVNS may exert anti-inflammatory effects through modulating the splenic α7nAchR/JAK2/STAT3 signaling pathway, thereby ameliorating LPS-induced depressive-like behavior in rats.
目的：观察经皮耳穴-迷走神经刺激（taVNS）对脂多糖（LPS）诱导抑郁样行为大鼠脾脏α7烟碱乙酰胆碱受体（α7nAchR）/ Janus激酶2（JAK2） /信号转导和转录激活因子3（STAT3）信号通路的影响，探讨taVNS抗抑郁的作用机制。方法：SD大鼠和α7nAchR基因敲除大鼠（简称α7）分别随机分为空白组、模型组、taVNS组，每组6只。SD taVNS组和α7 taVNS组每天进行1次30 min的taVNS干预（第1—9天）。通过腹腔注射1 mg/kg LPS（第8天）建立抑郁样行为大鼠模型。旷场实验记录干预后（第9天）大鼠旷场实验平均速度、活动时间和边上不动时间，采用电化学发光多因子方法检测大鼠血清白细胞介素（IL）-10、CXC趋化因子配体1 （CXCL1）含量，采用Western blot法检测各组大鼠脾脏磷酸化（p）-JAK2、p-STAT3蛋白表达。结果：与SD空白组比较，SD模型组大鼠旷场实验平均速度、活动时间，脾脏p-JAK2、p-STAT3蛋白表达量显著减少（P<0.01，P<0.05），边上不动时间，血清IL-10、CXCL1含量显著增加（P<0.001，P<0.01，P<0.05）；与SD模型组比较，SD taVNS组旷场实验平均速度、活动时间，脾脏p-JAK2、p-STAT3蛋白表达量显著增加（P<0.01，P<0.001），边上不动时间，血清IL-10、CXCL1含量显著减少（P<0.001，P<0.05）。与α7空白组比较，α7模型组旷场实验平均速度、活动时间，脾脏p-JAK2蛋白表达量显著减少（P<0.05，P<0.001，P<0.01），边上不动时间，血清IL-10、CXCL1含量显著增加（P<0.001，P<0.01）； α7模型组与α7 taVNS组各指标差异无统计学意义。与SD taVNS组比较，α7 taVNS组旷场实验边上不动时间、血清IL-10含量增加（P<0.001，P<0.05），脾脏p-JAK2、p-STAT3蛋白表达减少（P<0.01，P<0.05）。结论：taVNS可能通过调节脾脏α7nAchR/JAK2/STAT3信号通路发挥抗炎作用，从而改善LPS诱发的大鼠抑郁样行为。.
Keywords: Depression; Inflammation; Lipopolysaccharide; Transcutaneous auricular vagus nerve stimulation.