耳穴刺激经迷走神经对糖尿病合并抑郁大鼠行为学与BDNF-TrkB通路的影响  

Effects of transcutaneous vagus nerve stimulation on behavior and the BDNF-TrkB pathway in rats of diabetes combined with depression

作　　者：王艺霏 李少源[1] 王瑜 张金铃[1] 张紫璇 陈瑜 荣培晶[1] WANG Yi-fei;LI Shao-yuan;WANG Yu;ZHANG Jin-ling;ZHANG Zi-xuan;CHEN Yu;RONG Pei-jing(Institute of Acupucture and Moxibustion,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院针灸研究所,北京100700

出　　处：《中华中医药杂志》2022年第5期2639-2644,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：中国中医科学院科技创新工程项目(No.CI2021A03405);国家自然科学基金中德合作研究项目(No.GZ1236)。

摘　　要：目的:观察BDNF-TrkB通路被阻断后,耳穴刺激经迷走神经(taVNS)对糖尿病合并抑郁大鼠行为学与BDNF-TrkB通路蛋白表达的影响,并探讨taVNS抗抑郁的作用机制。方法:40只雄性SD大鼠随机分为空白组、模型组、taVNS组、taVNS+阻断剂组,每组10只。高脂饲料结合链脲菌素建立糖尿病合并抑郁大鼠模型。造模成功后开始在2%异氟烷吸入麻醉下给予taVNS组、阻断剂组大鼠采用韩氏电针仪给予taVNS干预,阻断剂组大鼠干预前30 min腹腔注射阻断剂K252a,共21 d。观察大鼠行为学(旷场运动和强迫游泳),ELISA法检测糖化血红蛋白(HbA1c)以及Western blotting法检测海马BDNF和TrkB蛋白表达水平。结果:高脂饲料结合STZ可诱导大鼠抑郁样行为,与模型组比较,taVNS组大鼠血清HbA1c显著降低(P<0.01),水平运动格数、垂直竖立次数显著增加(P<0.01),强迫游泳不动时间显著缩短(P<0.01),BDNF、TrkB蛋白表达显著升高(P<0.01);与taVNS组比较,阻断剂组大鼠血清HbA1c显著升高(P<0.05);水平运动格数和垂直竖立次数显著降低(P<0.01,P<0.05),强迫游泳不动时间显著增加(P<0.05);BDNF、TrkB蛋白表达显著降低(P<0.01)。结论:taVNS可能通过上调BDNF-TrkB通路蛋白表达水平,降低大鼠HbA1c,同时改善大鼠抑郁样行为。Objective:To observe the effect of transcutaneous auricular vagus nerve stimulation(taVNS)on the behavior and expression of BDNF-TrkB pathway in hippocampus of diabetic rats with depression after the BDNF-TrkB pathway blocked,and to explore the mechanism of antidepressant of taVNS.Methods:Forty male SD rats were randomly divided into blank group,model group,taVNS group and blocker group,10 rats in each group.High-fat diet combined with intraperitoneal injection of streptozotocin(STZ)to establish diabetic and depression model rats.After successful modeling,the rats in the taVNS group and the blocker group were given taVNS intervention under 2%isoflurane inhalation anesthesia,and the blocker group was injected intraperitoneally 30 min before the intervention of the rats in the blocker group K252a,21 days in total.The behaviors(open field exercise and forced swimming)were observed,serum glycosylated hemoglobin(HbA1c)was detected by ELISA,and expression levels of BDNF and TrkB proteins in the hippocampus were detected by Western blotting.Results:High-fat diet combined with STZ could induce depression-like behaviors in rats.Compared with the model group,the serum HbA1c in the taVNS group was significantly decreased(P<0.01),and the horizontal and vertical exercise scores were significantly increased(P<0.01),the immobility time of forced swimming was significantly decreased(P<0.01),and the protein expressions of BDNF and TrkB were significantly increased(P<0.01).Compared with the taVNS group,the serum HbA1c of the rats in the blocker group was significantly increased(P<0.05).The scores of horizontal movement and vertical movement were significantly decreased(P<0.01,P<0.05),and the immobility time of forced swimming was significantly increased(P<0.05);the protein expressions of BDNF and TrkB were significantly decreased(P<0.01).Conclusion:taVNS may improve the depression-like behavior of rats and reduce serum HbA1c by up-regulating the expression level of BDNF-TrkB pathway proteins in the hippocampus.

关 键 词：耳穴刺激经迷走神经 糖尿病 抑郁 BDNF-TrkB通路 行为学 糖化血红蛋白 

分 类 号：R245[医药卫生—针灸推拿学]