ABSTRACT
BACKGROUND: Pulmonary fibrosis is a progressive and usually lethal pulmonary disease. Despite considerable research efforts, no effective therapeutic strategy for pulmonary fibrosis has been developed. NecroX-5 has been reported to possess anti-inflammatory, anti-oxidative and anti-tumor activities. In the present study, we aimed to determine whether NecroX-5 exhibits antifibrotic property in bleomycin (BLM)-induced pulmonary fibrosis. RESULTS: We found that pre-treatment with NecroX-5 alleviated inflammatory response, reduced oxidative stress, inhibited epithelial-mesenchymal transition (EMT), and ameliorated pulmonary fibrosis in vivo and in vitro. Our data further indicated that NecroX-5 substantially reduced activation of NLRP3 inflammasome and TGF-ß1/Smad2/3 signaling in vivo and in vitro. Additionally, NLRP3 overexpression significantly reversed the protective effects of NecroX-5 in lung epithelial cells exposed to BLM. CONCLUSIONS: Overall, our results demonstrate the potent antifibrotic properties of NecroX-5 and its therapeutic potential for pulmonary fibrosis.
Subject(s)
Epithelial-Mesenchymal Transition , Heterocyclic Compounds, 4 or More Rings , NLR Family, Pyrin Domain-Containing 3 Protein , Pulmonary Fibrosis , Sulfones , Animals , Bleomycin , Epithelial-Mesenchymal Transition/drug effects , Heterocyclic Compounds, 4 or More Rings/pharmacology , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/pathology , Sulfones/pharmacology , Transforming Growth Factor beta1/metabolismABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of dexmedetomidine combined electrical stimulation on cognitive function of neurosurgical diseases patients treated by extracerebral intervention.</p><p><b>METHODS</b>Totally 122 patients with neurosurgical diseases who underwent selective intervention were randomly assigned to the observation group and the control group, 61 cases in each group. Patients in the control group recieved anesthesia by dexmedetomidine. Those in the observation group received electrical stimulation at Baihui (DU20), Yintang ( EX-HN3), and Neiguan (PC6) before dexmedetomidine anesthesia. The cognitive function of patients at preoperative day 1 and postoperative day 1 was respectively evaluated by Mini-Mental State Examinations (MMSE). Serum NSE, S-100β, IL-1β, IL-6, and TNF-α levels were detected in the two groups before intervention and immediately after intervention using ELISA.</p><p><b>RESULTS</b>MMSE scores of two groups were significantly reduced at post-intervention day 1, as compared with one day before intervention. MMSE score of the observation group at post-intervention day 1 was (23.15 ± 1.87) points, significantly higher than that of the control group [ (19.34 ± 1.64) points , (P < 0.05)]. The postoperative cognitive dysfunction (POCD) incidence rate of the observation group was 16.4% (10/61), significantly lower than that of the control group [39.3% (24/61); P < 0.05]. Compared with before intervention, NSE and S-100β protein levels, IL-1β, IL-6 and α-TNF levels of the two groups increased (P < 0.05). Post-intervention NSE and S-100β protein levels, IL-1β, IL-6 and α-TNF levels were significantly lower in the observation group than in the control group (P < 0.05).</p><p><b>CONCLUSION</b>Dexmedetomidine combied electrical stimulation could effectively prevent the occurrence of postoperative cognition, and reduce levels of NSA, S-100β, IL-1β, IL-6 and TNF-α.</p>
