经皮耳迷走神经刺激对脂多糖诱导的抑郁样行为大鼠脾脏α7nAchR/JAK2/STAT3信号通路的影响

[Effect of transcutaneous auricular vagus nerve stimulation on the splenic α7nAchR/JAK2/STAT3 signaling pathway in LPS-induced depressive-like behavior rats].

作者信息

Chen Yu, Wang Jun-Ying, Zhang Yue, Zhang Zi-Xuan, Wang Yi-Fei, Rong Pei-Jing

机构信息

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China.

出版信息

Zhen Ci Yan Jiu. 2023 Sep 25;48(9):933-8. doi: 10.13702/j.1000-0607.20220402.

DOI:10.13702/j.1000-0607.20220402

PMID:37730264

Abstract

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 (<0.01, <0.05, <0.001) and the side immobility time was increased (<0.001) in the open field test, serum IL-10 and CXCL1 levels were up-regulated (<0.01, <0.05, <0.001), and splenic p-JAK2 protein expressions were down-regulated (<0.05, <0.01) in SD and α7nAchR knockout rats, and splenic p-STAT3 protein expression were down-regulated (<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 (<0.01) and the side immobility time was decreased (<0.001) in the open field test, serum IL-10 and CXCL1 levels down-regulated (<0.05), while splenic p-JAK2 and p-STAT3 protein expressions were up-regulated (<0.01, <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 (<0.001, <0.05) side immobility time in the open field test and serum IL-10, decreased splenic p-JAK2 and p-STAT3 protein expressions (<0.01, <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.

摘要

目的

观察经皮耳迷走神经刺激（taVNS）对改善脂多糖（LPS）诱导的抑郁样行为大鼠的抑郁样行为及脾脏α7烟碱型乙酰胆碱受体（α7nAchR）/ Janus激酶2（JAK2）/信号转导及转录激活因子3（STAT3）信号通路的影响，以探讨taVNS的抗抑郁机制。

方法

将SD大鼠随机分为SD对照组、SD模型组和SD taVNS组，将α7nAchR基因敲除大鼠也随机分为α7对照组、α7模型组和α7 taVNS组，每组6只。通过腹腔注射LPS（1 mg/kg）建立抑郁样行为大鼠模型。SD taVNS组和α7 taVNS组大鼠分别在LPS注射前7天至LPS注射后2天每天接受一次taVNS干预（2 Hz/15 Hz，2 mA，30分钟）。taVNS后记录旷场试验中的平均速度、活动时间和静止时间。采用电化学发光多因子法检测血清中白细胞介素10（IL-10）和趋化因子（C-X-C基序）配体1（CXCL1）的含量。采用蛋白质免疫印迹法检测脾脏磷酸化（p）-JAK2和p-STAT3蛋白表达。

结果

与各自对照组相比，LPS注射后，SD大鼠和α7nAchR基因敲除大鼠在旷场试验中的平均速度和活动时间降低（<0.01，<0.05，<0.001），静止时间增加（<0.001），血清IL-10和CXCL1水平上调（<0.01，<0.05，<0.001），脾脏p-JAK2蛋白表达下调（<0.05，<0.01），SD大鼠脾脏p-STAT3蛋白表达下调（<0.05）。taVNS干预后，与模型组相比，SD taVNS组在旷场试验中的平均速度和活动时间增加（<0.01），静止时间减少（<0.001），血清IL-10和CXCL1水平下调（<0.05），而脾脏p-JAK2和p-STAT3蛋白表达上调（<0.01，<0.001），α7 taVNS组则未出现此现象。与SD taVNS组相比，α7 taVNS组在旷场试验中的静止时间增加（<0.001，<0.05），血清IL-10增加，脾脏p-JAK2和p-STAT3蛋白表达降低（<0.01，<0.05）。