ABSTRACT
This study aimed to investigate the effects of hypoxia on RhoA/Rho-kinase (ROCK) signaling pathway and autophagy in pulmonary artery smooth muscle cells (PASMCs), and to explore the underlying mechanism of Umbelliferone (Umb) in ameliorating chronic hypoxic pulmonary hypertension. PASMCs were cultured from Sprague-Dawley (SD) rats and randomly divided into control group, hypoxia group, hypoxia + Umb intervention group and normoxia + Umb intervention group. Alpha smooth muscle actin (α-SMA) and LC3 were assessed by immunofluorescence staining. Protein expression of RhoA, ROCK2, p-MYPT1, LC3-II, Beclin-1, p62, C-Caspase 3, Bax and Bcl-2 was analyzed by Western blotting. In in vivo study, SD rats were divided into control group, hypoxia group and hypoxia + Umb intervention group. Weight ratio of the right ventricle (RV)/left ventricle plus septum (LV+S) was detected, and pulmonary arterial morphological features were examined by HE staining. The results indicated that compared with the control group, the LC3-II/LC3-I ratio and expression of Beclin-1 were significantly increased, while p62 expression was significantly decreased, and the expressions of RhoA, ROCK2 and p-MYPT1 were significantly increased in PASMCs of hypoxia group (P < 0.05). The changes of LC3-II/LC3-I ratio, the expressions of Beclin-1, p62, RhoA, ROCK2 and p-MYPT1 in PASMCs were reversed by Umb treatment (P < 0.05). Consistently, the pulmonary arterial wall was thickened and the RV/(LV+S) ratio was increased in hypoxic rats, which were significantly improved by Umb treatment (P < 0.05). These results suggest that Umb can improve hypoxia-induced pulmonary hypertension by inhibiting the RhoA/ROCK signaling pathway and autophagy in PASMCs.
Subject(s)
Hypertension, Pulmonary , Animals , Autophagy , Beclin-1/metabolism , Beclin-1/pharmacology , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/etiology , Hypoxia/complications , Myocytes, Smooth Muscle/metabolism , Pulmonary Artery , Rats , Rats, Sprague-Dawley , Signal Transduction , Umbelliferones/metabolism , Umbelliferones/pharmacology , rho-Associated Kinases/metabolism , rho-Associated Kinases/pharmacologyABSTRACT
BACKGROUND: Wound infections after posterior spinal surgery are a troublesome complication; patients are occasionally forced to remove the internal fixation device, which can lead to instability of the spine and injury to the spinal cord. The purpose of this study was to evaluate the efficacy of modified vacuum-assisted closure (VAC) for treating an early postoperative spinal wound infection. METHODS: We conducted a retrospective study of 18 patients with wound infections after posterior spinal surgery from 2014 to 2017 at a single tertiary center. All patients included in the study received modified VAC treatment (VAC combined with a closed suction irrigation system, CSIS) until the wound satisfied the secondary closure conditions. Detailed information was obtained from the medical records. RESULTS: Wound size decreased significantly after 1 week of the modified VAC treatment. Three patients were treated with VAC three times and one patient received the VAC treatment four times; the remaining patients received the VAC treatment twice. The patients had excellent wound beds after an average of 8 days. The wound healed completely after an average of 17 days, and the average hospital stay was 33 days. There was no recurrence of infection at the 1-year follow-up. CONCLUSIONS: This study demonstrates that VAC combined with a CSIS is a safe, reliable, and effective method to treat a wound infection after spinal surgery. This improved VAC procedure provides an excellent wound bed to facilitate wound healing and shorten the hospital stay.
