Abstract：
Sympathetic hyperinnervation is the leading cause of fatal ventricular arrhythmia (VA) following myocardial infarction (MI). Cardiac mast cells cause arrhythmias directly through degranulation. However, the role and mechanism of mast cell degranulation in sympathetic remodeling remain unknown. We investigated the role of oxytocin (OT) in stabilizing cardiac mast cells and improving sympathetic innervation in rats. MI was induced by coronary artery ligation. Western blotting, immunofluorescence, and toluidine staining of mast cells were performed to determine the expression and location of target protein. Mast cells accumulated significantly in peri-infarcted tissues and were present in a degranulated state. They expressed OT receptor (OTR), and OT infusion reduced the number of degranulated cardiac mast cells post-MI. Sympathetic hyperinnervation was attenuated as assessed by immunofluorescence for tyrosine hydroxylase (TH). Seven days post MI, the arrhythmia score of programmed electrical stimulation was higher in vehicle-treated rats with MI than in rats treated with OT. An in vitro study showed that OT stabilized mast cells via the PI3K/AKT signaling pathway. Further in vivo studies on OTR-deficient mice showed worsening mast cell degranulation and worsening sympathetic innervation. OT pretreatment inhibited cardiac mast cell degranulation post MI and prevented sympathetic hyperinnervation, along with mast cell stabilization via the PI3K/AKT pathway.Significance Statement 1.We confirmed the role and mechanism of oxytocin (OT) in stabilizing cardiac mast cells. 2. It is the first study to elucidate the mechanism of oxytocin (OT)-mediated sympathetic hyperinnervation post-myocardial infarction (MI).
摘要：
交感神经支配过度是心肌梗死（MI）后致命性室性心律失常（VA）的主要原因。心脏肥大细胞直接通过脱颗粒引起心律失常。然而,肥大细胞脱颗粒在交感神经重构中的作用和机制尚不清楚。我们研究了催产素（OT）在稳定大鼠心脏肥大细胞和改善交感神经支配中的作用。冠状动脉结扎诱发MI。西方印迹,免疫荧光，对肥大细胞进行甲苯胺染色以确定靶蛋白的表达和定位。肥大细胞在梗塞周围组织中明显积累，并以脱颗粒状态存在。他们表达OT受体（OTR），和OT输注减少了MI后脱颗粒心脏肥大细胞的数量。通过酪氨酸羟化酶（TH）的免疫荧光评估，交感神经支配过度减弱。MI后七天，接受媒介物治疗的MI大鼠的程序化电刺激的心律失常评分高于接受OT治疗的大鼠.体外研究表明，OT通过PI3K/AKT信号通路稳定肥大细胞。对OTR缺陷小鼠的进一步体内研究表明，肥大细胞脱颗粒恶化，交感神经支配恶化。OT预处理抑制MI后心脏肥大细胞脱颗粒并防止交感神经支配过度，通过PI3K/AKT途径稳定肥大细胞。意义声明1.我们证实了催产素（OT）在稳定心脏肥大细胞中的作用和机制。2.这是阐明催产素（OT）介导的交感神经支配在心肌梗死（MI）后的机制的第一项研究。
