经皮迷走神经刺激可改善慢性应激大鼠的心脏异常。

Transcutaneous vagus nerve stimulation ameliorates cardiac abnormalities in chronically stressed rats.

机构信息

Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, (A Central University), Vidya Vihar, Raebareli Road, Lucknow, U.P., 226025, India.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Jan;397(1):281-303. doi: 10.1007/s00210-023-02611-5. Epub 2023 Jul 8.

Abstract

Chronically stressed patients often have low vagal tone and increased levels of proinflammatory cytokines, which increase their risk for developing cardiac dysfunction. Transcutaneous vagus nerve stimulation (taVNS) is a way to activate the parasympathetic system, which has the ability to reduce inflammation and antagonize excessive sympathetic responses. However, the effectiveness of taVNS in treating cardiac dysfunction caused by chronic unpredictable stress (CUS) has not been studied. To investigate this, we first validated a rat model of CUS, in which the rats were exposed to random stressors daily for 8 weeks. Post CUS, the rats were treated with taVNS (1.0 ms, 6 V, 6 Hz, for 40 min × 2 weeks, alternatively) and their cardiac function and cholinergic flow were evaluated. Furthermore, serum cardiac troponin I (cTnI), cardiac caspase-3, inducible nitric oxide synthase (iNOS), and transforming growth factor (TGF)-β1 expression in rats were also assessed. The chronically stressed rats showed depressed behavior with increased levels of serum corticosterone and proinflammatory cytokines. Electrocardiogram (ECG) and heart rate variability (HRV) studies revealed elevated heart rate, diminished vagal tone, and altered sinus rhythm in CUS rats. Furthermore, the CUS rats demonstrated cardiac hypertrophy and fibrosis with increased caspase-3, iNOS, and TGF-β expression in their myocardium and increased levels of serum cTnI. Interestingly, alternate taVNS therapy for 2 weeks, post CUS, helped alleviate these cardiac abnormalities. These suggest that taVNS could be a useful adjunctive and non-pharmacological approach for managing CUS induced cardiac dysfunction.

摘要

慢性应激患者常伴有迷走神经张力降低和促炎细胞因子水平升高,这会增加其发生心功能障碍的风险。经皮迷走神经刺激(taVNS)是一种激活副交感神经系统的方法,该系统具有减轻炎症和拮抗过度交感反应的能力。然而,taVNS 治疗慢性不可预测应激(CUS)引起的心功能障碍的效果尚未得到研究。为了研究这一点,我们首先验证了 CUS 大鼠模型,该模型中大鼠每天接受随机应激源刺激 8 周。CUS 后,大鼠接受 taVNS(1.0 ms,6 V,6 Hz,40 min×2 周,交替)治疗,并评估其心功能和胆碱能流。此外,还评估了大鼠血清心肌肌钙蛋白 I(cTnI)、心肌半胱天冬酶-3、诱导型一氧化氮合酶(iNOS)和转化生长因子-β1(TGF-β1)的表达。慢性应激大鼠表现出抑郁行为,血清皮质酮和促炎细胞因子水平升高。心电图(ECG)和心率变异性(HRV)研究显示,CUS 大鼠的心率升高、迷走神经张力降低、窦性节律改变。此外,CUS 大鼠还表现出心肌肥大和纤维化,心肌中半胱天冬酶-3、iNOS 和 TGF-β1 的表达增加,血清 cTnI 水平升高。有趣的是,CUS 后接受 2 周交替 taVNS 治疗有助于缓解这些心脏异常。这些结果表明,taVNS 可能是治疗 CUS 引起的心功能障碍的一种有用的辅助和非药物治疗方法。

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