RESUMEN

MicroRNAs (miRs) are implicated in heart failure (HF). Thereby, we aim to uncover the role of miR-144-3p in HF. Doxorubicin (Dox)-induced HF model was constructed in rats and cardiomyocytes H9C2, and the cardiac function was determined using ultrasound cardiogram. Morphology of cardiac tissue was observed using hematoxylin-eosin (H&E) staining. The viability and apoptosis of Dox-treated and transfected cardiomyocytes were determined using Cell Counting Kit-8 (CCK-8) assay and flow cytometry. Relative expressions of the HF-associated miRs (including miR-144-3p), suppressor of cytokine signaling 2 (SOCS2), apoptosis- and phosphoinositide 3-kinase (PI3K)/AKT pathway-related factors (B-cell lymphoma 2, Bcl-2; Bcl-2 associated X protein, Bax; cleaved [C] capsase-3; phosphoinositide 3-kinase, PI3K; phosphorylated-PI3K, p-PI3K; p-AKT; AKT) were measured with quantitative real-time polymerase chain reaction or Western blot. Target gene of miR-144-3p was predicted by Starbase and TargetScan and confirmed with dual-luciferase reporter assay. Dox caused rat cardiac dysfunction, aggravated cardiac injury, decreased cardiomyocytes viability, and the expression of miR-144-3p, Bcl-2, and phosphorylation of both PI3K and AKT yet the upregulated those of Bax and C caspase-3, which was reversed by upregulating miR-144-3p, whereas downregulating miR-144-3p did oppositely. SOCS2 was the target gene of miR-144-3p, Dox promoted SOCS2 expression, which was reversed by upregulating miR-144-3p, while downregulating miR-144-3p did conversely. In addition, silencing SOCS2 reversed the effects of miR-144-3p downregulation in Dox-treated cardiomyocytes. Upregulating miR-144-3p alleviated Dox-induced cardiac dysfunction and cell apoptosis via targeting SOCS2, providing a novel evidence of miR-144-3p in HF.

Asunto(s)

Insuficiencia Cardíaca , MicroARNs , Ratas , Animales , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasa/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Apoptosis , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Doxorrubicina/farmacología , Doxorrubicina/metabolismo , Insuficiencia Cardíaca/inducido químicamente , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Supresoras de la Señalización de Citocinas/genética , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Proteínas Supresoras de la Señalización de Citocinas/farmacología

RESUMEN

To compare the differences between asleep and awake robot-assisted deep brain stimulation (DBS) surgery for Parkinson's Disease (PD), we conducted this retrospective cohort study included 153 PD patients undergoing bilateral robot-assisted DBS from June 2017 to August 2019, of which 58 cases were performed under general anesthesia (GA) and 95 cases under local anesthesia (LA). Procedure duration, stimulation parameters, electrode implantation accuracy, intracranial air, intraoperative electrophysiological signal length, complications, and Unified PD Rating Scale (UPDRS) measurements were recorded and compared. The clinical evaluation was conducted by two raters who were blinded to the choice of anesthesia. Procedure duration was significantly shorter in the GA group, while on stimulation off medication motor scores (UPDRS-III) were significantly improved in both the GA and LA group. ANCOVA covariated for the baseline UPDRS-III and levodopa challenge exhibited no significant differences. In terms of amplitude, frequency, and pulse width, the stimulation parameters used for DBS power-on were similar. There were no significant differences in electrode implantation accuracy, intraoperative electrophysiological signal length, or intracerebral hemorrhage (no occurrences in either group). The pneumocephalus volume was significantly smaller in the GA group. Six patients exhibited transient throat discomfort associated with tracheal intubation in the GA group. The occurrence of surgical incision infection was similar in both groups. Compared with the awake group, the asleep group exhibited a shorter procedure duration with a similar electrode implantation accuracy and short-term motor improvement. Robot-assisted asleep DBS surgery is a promising surgical method for PD.