Therapeutic effect of vagus nerve stimulation on depressive-like behavior, hyperglycemia and insulin receptor expression in Zucker fatty rats.
Therapeutic effect of vagus nerve stimulation on depressive-like behavior, hyperglycemia and insulin receptor expression in Zucker fatty rats.
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迷走神经刺激对 Zucker 肥胖大鼠抑郁样行为、高血糖和胰岛素受体表达的治疗作用
DOI：
10.1371/journal.pone.0112066
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang S
中科院分区：
文献类型：
--
作者：
Li S;Zhai X;Rong P;McCabe MF;Wang X;Zhao J;Ben H;Wang S
抑郁症和2型糖尿病(T2D)是临床上常见的并存疾病，发病机制尚不清楚。Zucker糖尿病肥胖(ZDF，fa/fa)大鼠天生就会发生T2D伴高血糖和高胰岛素血症。在这里，我们研究了ZDF大鼠是否也有先天性抑郁症，抑郁症与T2D之间的相关性，是否与胰岛素受体(IR)的表达有关，以及经皮耳迷走神经刺激(TaVNS)是否有助于改善这种共病。6周龄雄性ZDF和Zucker瘦肉型(ZL，FA/+)仔猪随机分为单纯组(ZDF，n = 6；ZL，n = 7)和taVNS组(ZDF-taVNS，n = 8；ZL-taVNS，n = 6)。TaVNS组麻醉下每日1次，30min-taVNS，连续34d。每周检测一次血糖，第35天测定血浆糖化血红蛋白(HbAlc)水平和强迫游泳不动时间。免疫组化和Western印迹法检测胰岛素受体(IR)在不同组织中的表达。我们发现，幼稚的ZDF大鼠稳定地出现高血糖。ZDF大鼠的不动时间延长与血浆HbAlC水平升高呈显著正相关。长期的taVNS治疗可同时阻止ZDF大鼠抑郁样行为的发展和高血糖的进展。单纯ZDF组大鼠各组织中IR的表达均低于单纯ZL组和长期给药组。综上所述，我们的结果表明，在ZDF大鼠中，1)抑郁和T2D同时发生，2)不动时间与HbAlc浓度呈高度正相关，3)IR的低表达可能参与了抑郁症和T2D的共病，以及4)taVNS的抗糖尿病和抗抑郁作用可能是通过IR表达上调实现的。
Depression and type 2 diabetes (T2D) are common comorbid diseases and highly prevalent in the clinical setting with an unclarified mechanism. Zucker diabetic fatty (ZDF, fa/fa) rats natively develop T2D with hyperglycemia and hyperinsulinemia. Here we studied whether ZDF rats also innately develop depression, what a correlation is between depression and T2D, whether insulin receptor (IR) expression is involved in, and whether transcutaneous auricular vagus nerve stimulation (taVNS) would be beneficial in amelioration of the comorbidity. Six week old male ZDF and Zucker lean (ZL, fa/+) littermates were randomly divided into naïve (ZDF, n = 6; ZL, n = 7) and taVNS (ZDF-taVNS, n = 8; ZL-taVNS, n = 6) groups. Once daily 30 min-taVNS sessions were administrated under anesthesia for 34 consecutive days in taVNS groups. Blood glucose levels were tested weekly, and plasma glycosylated hemoglobin (HbAlc) level and immobility time in forced swimming test were determined on day 35 in all groups. The expression of insulin receptor (IR) in various tissues was also detected by immunostaining and Western blot. We found that naïve ZDF rats developed hyperglycemia steadily. These ZDF rats showed a strong positive correlation between longer immobility time and higher plasma HbAlC level. Long term taVNS treatment simultaneously prevented the development of depression-like behavior and progression of hyperglycemia in ZDF rats. The expression of IR in various tissues of naïve ZDF rats is lower than in naïve ZL and long-term taVNS treated ZDF rats. Collectively, our results indicate that in ZDF rats, i) depression and T2D develop simultaneously, ii) immobility time and HbAlc concentrations are highly and positively correlated, iii) a low expression of IR may be involved in the comorbidity of depression and T2D, and iv) taVNS is antidiabetic and antidepressive possibly through IR expression upregulation.
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影响因子：
8.2
作者：
Langenberg C;Pascoe L;Mari A;Tura A;Laakso M;Frayling TM;Barroso I;Loos RJ;Wareham NJ;Walker M;RISC Consortium
通讯作者：
RISC Consortium
DOI：
10.1161/hypertensionaha.110.160671
发表时间：
2011-03
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Ward KR;Bardgett JF;Wolfgang L;Stocker SD
通讯作者：
Stocker SD
影响因子：
82.9
作者：
Smyth, S;Heron, A
通讯作者：
Heron, A
影响因子：
13.5
作者：
Banks, William A.;Owen, Joshua B.;Erickson, Michelle A.
通讯作者：
Erickson, Michelle A.
影响因子：
--
作者：
Huang F;Dong J;Kong J;Wang H;Meng H;Spaeth RB;Camhi S;Liao X;Li X;Zhai X;Li S;Zhu B;Rong P
通讯作者：
Rong P