Rehabilitation Medicine Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Intelligent Rehabilitation Research Center, International Institute for Acupuncture and Rehabilitation, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; The Provincial Key Laboratory for Acupuncture and Rehabilitation in Zhejiang Province, The Wenzhou Key Laboratory for Rehabilitation Research, China.
Rehabilitation Medicine Center, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
Int Immunopharmacol. 2024 Sep 30;139:112714. doi: 10.1016/j.intimp.2024.112714. Epub 2024 Jul 27.
Ischemic stroke is one of the leading causes of chronic disability worldwide, and stroke-induced heart damage can lead to death. According to research, patients with a variety of brain disease have good clinical results after vagus nerve stimulation (VNS). After ischemic stroke, mast cells (MCs) degranulate and release a large number of mediators, which may cause systemic inflammation. Chymase secreted by MCs can increase the levels of pathological angiotensin II (AngⅡ), which plays a crucial role in the deterioration of heart disease. Our goal was to develop a minimally invasive, targeted, and convenient VNS approach to assess the impact of VNS and to clarify the relationship between VNS and MCs in the prognosis of patients with myocardial atrophy after acute ischemic stroke.
In this study, we verified the role of VNS in the treatment of myocardial atrophy after stroke and its molecular mechanism using a rat model of middle cerebral artery occlusion (MCAO/r). Behavioral studies were assessed using neurobehavioral deficit scores. Enzyme-linked immunosorbent assays, immunofluorescence staining, Western blotting and qRT-PCR were used to analyze the expression levels of myocardial atrophy, MC and inflammatory markers in rat hearts.
VNS improved myocardial atrophy in MCAO/r rats, inhibited MC activation, reduced the expression of chymase and AngⅡ, and inhibited the expression of proinflammatory factors. The chymase activator C48/80 reversed these effects of VNS. Chymase activation inhibited the effect of VNS on myocardial atrophy in MCAO/r rats, increased AngⅡ expression and aggravated inflammation and autophagy. The myocardial atrophy of MCAO/r rats was improved after chymase inhibition, and AngⅡ expression, inflammation and autophagy were reduced. Our results suggest that VNS may reduce the expression of chymase and AngⅡ by inhibiting MC activation, thereby improving myocardial atrophy and reducing inflammation and autophagy in MCAO/r rats. Inhibition of MC activation may be an effective strategy for treating myocardial atrophy after stroke.
VNS inhibits MC activation and reduces the expression of chymase and AngII, thereby alleviating myocardial atrophy, inflammation and autophagy after stroke.
缺血性中风是全球慢性残疾的主要原因之一，中风引起的心脏损伤可导致死亡。根据研究，患有多种脑部疾病的患者在接受迷走神经刺激（VNS）后具有良好的临床效果。在缺血性中风后，肥大细胞（MCs）脱颗粒并释放大量介质，这可能导致全身炎症。MCs 分泌的糜蛋白酶可增加病理性血管紧张素 II（AngⅡ）的水平，在心脏病恶化中起关键作用。我们的目标是开发一种微创、靶向和方便的 VNS 方法来评估 VNS 的影响，并阐明 VNS 与 MCs 之间在急性缺血性中风后心肌萎缩患者预后中的关系。
在这项研究中，我们使用大脑中动脉闭塞（MCAO/r）大鼠模型验证了 VNS 在中风后心肌萎缩治疗中的作用及其分子机制。使用神经行为缺陷评分评估行为研究。酶联免疫吸附测定、免疫荧光染色、Western blot 和 qRT-PCR 用于分析大鼠心脏中心肌萎缩、MC 和炎症标志物的表达水平。
VNS 改善了 MCAO/r 大鼠的心肌萎缩，抑制了 MC 激活，降低了糜蛋白酶和 AngⅡ的表达，并抑制了促炎因子的表达。C48/80 是糜蛋白酶的激活剂，逆转了 VNS 的这些作用。糜蛋白酶激活抑制了 VNS 对 MCAO/r 大鼠心肌萎缩的作用，增加了 AngⅡ的表达并加重了炎症和自噬。MCAO/r 大鼠的心肌萎缩在糜蛋白酶抑制后得到改善，AngⅡ表达、炎症和自噬减少。我们的结果表明，VNS 可能通过抑制 MC 激活来降低糜蛋白酶和 AngⅡ的表达，从而改善 MCAO/r 大鼠的心肌萎缩并减少炎症和自噬。抑制 MC 激活可能是治疗中风后心肌萎缩的有效策略。
VNS 抑制 MC 激活，降低糜蛋白酶和 AngⅡ的表达，从而减轻中风后心肌萎缩、炎症和自噬。
