ABSTRACT
The current research aimed to study the effects of dexmedetomidine (DEX) pretreatment on rats with sepsis-induced acute kidney injury (SAKI) and miR-146a expression. The model of SAKI was established through the tail vein injection of lipopolysaccharide (LSP). We used an automatic biochemical analyzer to detect serum urea nitrogen (BUN) and creatinine (Cre) levels. The expression levels of urine KIM-1 and NGAL and serum IL-1ß and IL-6 were analyzed by enzyme-linked immunosorbent assay (ELISA). The content and activity of superoxide dismutase (SOD) were detected by the xanthine oxidase method. The content of malondialdehyde (MDA) was determined by the thiobarbituric acid (TBA) method. Reactive oxygen species (ROS) was detected by fluorescent probe DCFH-DA. Catalase (CAT) was detected by potassium permanganate titration. The expression level of miR-146a in the renal tissue and serum was detected by RT-PCR. The expression levels of Nrf2 and HO-1 proteins were detected by Western blot. Compared with those in the model group, rats in the DEX group had significantly lower expression levels of serum BUN, Cre, IL-1ß, and IL-6, and oxidant markers MDA and ROS, but significantly higher expression levels of miR-146a and antioxidant markers SOD and CAT. DEX pretreatment could improve the kidney morphology, injury severity, and Nrf2 and HO-1 proteins of rats with SAKI. In conclusion, DEX can improve oxidative stress and inflammatory responses in rats with SAKI, reduce the severity of the renal injury, and up-regulate the expression level of miR-146a.
Subject(s)
Acute Kidney Injury/drug therapy , Dexmedetomidine/therapeutic use , MicroRNAs/metabolism , Sepsis/pathology , Acute Kidney Injury/etiology , Acute Kidney Injury/pathology , Animals , Blood Urea Nitrogen , Catalase/genetics , Catalase/metabolism , Creatinine/blood , Dexmedetomidine/pharmacology , Heme Oxygenase (Decyclizing)/metabolism , Interleukin-1beta/blood , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/blood , Interleukin-6/genetics , Interleukin-6/metabolism , Kidney/metabolism , Kidney/pathology , Lipopolysaccharides/toxicity , Malondialdehyde/metabolism , MicroRNAs/blood , NF-E2-Related Factor 2/metabolism , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Sepsis/complications , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolismABSTRACT
OBJECTIVE: To investigate the effects of sustained inhalation of sevoflurane on cognitive function and the expression of oxidative stress response proteins such as NADPH oxidase subunits NOX2 and NOX4 in elderly patients undergoing radical surgery for lung cancer. STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Department of Anesthesiology, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, China, from February 2016 to October 2017. METHODOLOGY: Elderly patients who underwent radical surgery for lung cancer were divided into the sevoflurane group and the propofol group, with 52 cases in each group. Sustained inhalation of sevoflurane and propofol was administered to maintain anesthesia in the respective groups. Cognitive function and lung function parameters were compared between the two groups. Serum S100 β levels and expression of NOX2 and NOX4 proteins in peripheral blood mononuclear cells of the two groups were determined. RESULTS: At 24 hours after surgery, the lung function indices of the sevoflurane group such as FEV1, FVC and VC were higher than those of the propofol group (p<0.001, p=0.008 and p=0.002, respectively). At the end of the surgery and at 24 hours after surgery, the MMSE scores of the sevoflurane group were higher than the propofol group (all p<0.001). S100ï¢ levels were lower than the propofol group (p=0.003 and p<0.001, respectively). Levels of NADPH oxidase subunits NOX2 and NOX4 proteins in peripheral blood mononuclear cells of the sevoflurane group were lower than the propofol group (p=0.033, p<0.001, p<0.001and p<0.001, respectively). CONCLUSION: Compared with intravenous anesthesia with propofol, general anesthesia with sevoflurane inhalation has little effect on the short-term cognitive function in elderly patients undergoing radical surgery for lung cancer, and can effectively improve lung function. The mechanism may be related to the reduction of the expression of NOX2 and NOX4 proteins.
