Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: VNS inhibits MC activation and reduces the expression of chymase and AngII, thereby alleviating myocardial atrophy, inflammation and autophagy after stroke.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: VNS inhibits MC activation and reduces the expression of chymase and AngII, thereby alleviating myocardial atrophy, inflammation and autophagy after stroke.
摘要：
背景：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会导致死亡。根据研究,多种脑部疾病患者经迷走神经电刺激(VNS)治疗后临床效果良好。缺血性中风后，肥大细胞（MC）脱颗粒并释放大量介质，这可能会引起全身炎症。MCs分泌的糜蛋白酶可增加病理性血管紧张素Ⅱ(AngⅡ)的水平,这在心脏病的恶化中起着至关重要的作用。我们的目标是开发一种微创技术，有针对性的,和方便的VNS方法来评估VNS的影响，并阐明VNS和MC在急性缺血性卒中后心肌萎缩患者预后中的关系。
方法：在本研究中，我们使用大脑中动脉闭塞（MCAO/r）大鼠模型验证了VNS在治疗中风后心肌萎缩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，采用Westernblotting和qRT-PCR分析心肌萎缩的表达水平,大鼠心脏中的MC和炎症标志物。
结果：VNS改善MCAO/r大鼠心肌萎缩，抑制MC激活，减少糜蛋白酶和AngⅡ的表达，抑制促炎因子的表达。糜蛋白酶激活剂C48/80逆转了VNS的这些作用。糜酶激活抑制VNS对MCAO/r大鼠心肌萎缩的影响,AngⅡ表达增加,加重炎症和自噬。抑制糜蛋白酶后MCAO/r大鼠心肌萎缩得到改善,AngⅡ表达式,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大鼠心肌萎缩，减轻炎症和自噬。抑制MC激活可能是治疗中风后心肌萎缩的有效策略。
结论：VNS抑制MC的激活，降低糜蛋白酶和AngII的表达，从而减轻心肌萎缩，中风后的炎症和自噬。
方法：在本研究中，我们使用大脑中动脉闭塞（MCAO/r）大鼠模型验证了VNS在治疗中风后心肌萎缩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，采用Westernblotting和qRT-PCR分析心肌萎缩的表达水平,大鼠心脏中的MC和炎症标志物。
结果：VNS改善MCAO/r大鼠心肌萎缩，抑制MC激活，减少糜蛋白酶和AngⅡ的表达，抑制促炎因子的表达。糜蛋白酶激活剂C48/80逆转了VNS的这些作用。糜酶激活抑制VNS对MCAO/r大鼠心肌萎缩的影响,AngⅡ表达增加,加重炎症和自噬。抑制糜蛋白酶后MCAO/r大鼠心肌萎缩得到改善,AngⅡ表达式,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大鼠心肌萎缩，减轻炎症和自噬。抑制MC激活可能是治疗中风后心肌萎缩的有效策略。
结论：VNS抑制MC的激活，降低糜蛋白酶和AngII的表达，从而减轻心肌萎缩，中风后的炎症和自噬。
