Zhang Zhen, Dai Xinlun, Qi Ji, Ao Yu, Yang Chunfeng, Li Yumei
Department of PICU, The First Hospital of Jilin University, Changchun, China.
Clinical Medical College, Jilin University, Changchun, China.
Front Pediatr. 2018 Jun 21;6:139. doi: 10.3389/fped.2018.00139. eCollection 2018.
Viral myocarditis (VMC) is a common cardiac disease, however, there still lacks an effective therapeutic strategy for VMC. (AB), a Chinese herb with some functional metabolites, may have some pharmacological effects on VMC. AB ingredients were measured by a full-scan LCQ mass spectrum. We aimed to explore the effects of AB on the VMC children by investigating peripheral Treg cell homeostasis. A total of 68 VMC children were random and evenly assigned into an AG group (received 10-mL AB oral liquid daily), and a CG group (received placebo daily). Peripheral blood mononuclear cells (PBMC) were obtained from peripheral blood and Treg cells were isolated. The levels of miR-146b, miR-155, Treg immunity activity and myocarditis biomarkers were measured in Treg cells. There were four main components (sucrose, calycosin, Astragaloside IV and calycosin-7-glucoside) in AB. The cases sinus tachycardia, frequent premature ventricular contractions, and supraventricular tachycardia were significantly reduced in the AG group ( < 0.05). Meanwhile, the myocardial enzymes and cardiac function indexes were improved in the AG group when compared with the CG group ( < 0.05). The time of electrocardiogram recovery, symptom duration and hospital stay was shorter in the AG group than in the CG group ( < 0.05). The levels of miR-146b and miR-155 were higher in the CG group than in the AG group ( < 0.05). The levels of ROR-γt (retinoic acid receptor-related orphan nuclear receptor gamma), FoxP3 (forkhead transcription factor), IL-10 (interleukin-11) and TGF-β (transforming growth factor beta) were lower in the CG group than in the AG group ( < 0.05). In contrast, the levels of IL-17, IL-21, CK-MB (creatine kinase-MB), cTnI (cardiac troponin I), GrB (granzyme B), sFasL (soluble fas ligand) and caspase-3 were higher in the CG group than in the AG group ( < 0.05). Furthermore, the levels of ROR-γt, FoxP3, IL-10, and TGF-β were positively, whereas the levels of IL-17, IL-21, CK-MB, cTnI, GrB, sFasL and caspase-3 were negatively, associated with the levels of miR-146b and miR-155 ( < 0.05). AB treatment improved cardiac functions, peripheral Treg cell immunity imbalance in the children with VMC by reducing the levels of miR-146b and miR-155.
病毒性心肌炎（VMC）是一种常见的心脏疾病，然而，目前仍缺乏针对VMC的有效治疗策略。黄芪（AB）是一种含有多种功能性代谢产物的中药，可能对VMC具有一定药理作用。采用全扫描LCQ质谱仪测定AB成分。我们旨在通过研究外周调节性T细胞（Treg）稳态来探讨AB对VMC患儿的影响。将68例VMC患儿随机平均分为AG组（每日口服10 mL AB口服液）和CG组（每日口服安慰剂）。采集外周血获取外周血单个核细胞（PBMC）并分离Treg细胞。检测Treg细胞中miR-146b、miR-155水平、Treg免疫活性及心肌炎生物标志物。AB中含有四种主要成分（蔗糖、毛蕊异黄酮、黄芪甲苷和毛蕊异黄酮-7-葡萄糖苷）。AG组窦性心动过速、频发室性早搏和室上性心动过速病例明显减少（P<0.05）。同时，与CG组相比，AG组心肌酶和心功能指标得到改善（P<0.05）。AG组心电图恢复时间、症状持续时间和住院时间均短于CG组（P<0.05）。CG组miR-146b和miR-155水平高于AG组（P<0.05）。CG组维甲酸受体相关孤儿核受体γ（ROR-γt）、叉头转录因子（FoxP3）、白细胞介素-10（IL-10）和转化生长因子β（TGF-β）水平低于AG组（P<0.05）。相反，CG组白细胞介素-17、白细胞介素-21、肌酸激酶同工酶（CK-MB）、心肌肌钙蛋白I（cTnI）、颗粒酶B（GrB）、可溶性Fas配体（sFasL）和半胱天冬酶-3水平高于AG组（P<0.05）。此外，ROR-γt、FoxP3、IL-10和TGF-β水平与miR-146b和miR-155水平呈正相关，而白细胞介素-17、白细胞介素-21、CK-MB、cTnI、GrB、sFasL和半胱天冬酶-3水平与miR-146b和miR-155水平呈负相关（P<0.05）。AB治疗通过降低miR-146b和miR-155水平改善了VMC患儿的心功能和外周Treg细胞免疫失衡。
