Macrophage activation in stellate ganglia contributes to lung injury-induced arrhythmogenesis in male rats.
Macrophage activation in stellate ganglia contributes to lung injury-induced arrhythmogenesis in male rats.
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星状神经节中的巨噬细胞活化有助于雄性大鼠肺损伤诱导的肺发育。
DOI：
10.1111/apha.13657
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发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
Wang HJ
中科院分区：
文献类型：
--
作者：
Hong J;Adam RJ;Gao L;Hahka T;Xia Z;Wang D;Nicholas TA;Zucker IH;Lisco SJ;Wang HJ
急性肺损伤(ALI)患者发生心律失常的风险很高。我们推测星状神经节(SG)神经炎症参与了ALI所致的心律失常。我们建立了一种ALI大鼠模型，采用单次气管内滴注博莱霉素(2.5 mg/kg)的方法，并以生理盐水作为假对照。我们用植入放射遥测仪记录了口服米诺环素(20 mg/kg/d)和不口服米诺环素(20 mg/kg/d)的雄性博莱霉素和假手术大鼠的心电图。米诺环素是一种抑制小胶质细胞/巨噬细胞激活的抗炎药物。通过电生理学实验评价SG神经元的兴奋性。心电数据显示，在诱导后1-3周，博莱霉素组大鼠的自发性室性早搏(PVCs)明显多于假手术组，长期口服米诺环素可减轻这一现象。博莱霉素组大鼠海马区IBA1阳性巨噬细胞数和干扰素调节因子8蛋白表达最早在染毒后1周开始显著增加，并持续至少4周，米诺环素对此作用基本减弱。心率变异性分析显示博莱霉素治疗后的头两周内自主神经失衡，米诺环素显著减轻了这种失衡。电刺激分散的SG可引起博莱霉素组大鼠较假手术组和博莱霉素+米诺环素组大鼠更多的室上性心动过速。膜片钳数据显示，博莱霉素组大鼠海马神经元兴奋性增强，米诺环素可减弱这种兴奋性。脂多糖(LPS)处理的巨噬细胞与正常的海马神经元共培养可增强海马神经元的兴奋性。脑海马巨噬细胞的激活参与了博莱霉素性ALI雄性大鼠心律失常的发生。
Patients suffering from acute lung injury (ALI) are at high risk of developing cardiac arrhythmias. We hypothesized that stellate ganglia (SG) neural inflammation contributes to ALI-induced arrhythmia. We created an ALI rat model using a single tracheal instillation of bleomycin (2.5 mg/kg), with saline as a sham control. We recorded ECGs by implanted radiotelemetry in male bleomycin and sham rats treated with and without oral minocycline (20 mg/kg/d), an anti-inflammatory drug that inhibits microglia/macrophage activation. The SG neuronal excitability was assessed by electrophysiology experiments. ECG data showed that bleomycin-exposed rats exhibited significantly more spontaneous premature ventricular contractions (PVCs) from 1- to 3-week post-induction compared with sham rats, which was mitigated by chronic oral administration of minocycline. The bleomycin-exposed rats displayed a robust increase in both the number of Iba1-positive macrophages and protein expression of interferon regulatory factor 8 in the SG starting as early at 1-week post-exposure and lasted for at least 4 weeks, which was largely attenuated by minocycline. Heart rate variability analysis indicated autonomic imbalance during the first 2-week post-bleomycin, which was significantly attenuated by minocycline. Electrical stimulation of the decentralized SG triggered more PVCs in bleomycin-exposed rats than sham and bleomycin + minocycline rats. Patch-clamp data demonstrated enhanced SG neuronal excitability in the bleomycin-exposed rats, which was attenuated by minocycline. Co-culture of lipopolysaccharide (LPS)-pretreated macrophages with normal SG neurons enhanced SG neuronal excitability. Macrophage activation in the SG contributes to arrhythmogenesis in bleomycin-induced ALI in male rats.
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影响因子：
4
作者：
Carnevali L;Sgoifo A
通讯作者：
Sgoifo A
影响因子：
20.1
作者：
Fukuda K;Kanazawa H;Aizawa Y;Ardell JL;Shivkumar K
通讯作者：
Shivkumar K
影响因子：
82.9
作者：
Cao Z;Lis R;Ginsberg M;Chavez D;Shido K;Rabbany SY;Fong GH;Sakmar TP;Rafii S;Ding BS
通讯作者：
Ding BS
影响因子：
3.7
作者：
Kusunoki, Yuji;Nakamura, Toshie;Kida, Kozui
通讯作者：
Kida, Kozui
影响因子：
3.3
作者：
Jacono, F. J.;Peng, Y. -J.;Prabhakar, N. R.
通讯作者：
Prabhakar, N. R.