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Objective:To evaluate the effects of esketamine on myocardial injury and the relationship with nuclear factor-erythroid 2-related factor 2 (Nrf2) heme oxygenase-1 (HO-1) signaling pathway in septic rats.Methods:Thirty-two SPF healthy adult male Sprague-Dawley rats, weighing 200-230 g, were randomized into 4 groups ( n=8 each) using a random number table method: control group (group C), control plus esketamine group (group CE), sepsis group (group S) and sepsis plus esketamine group (group SE). Lipopolysaccharide (LPS) 10 mg/kg was intraperitoneally injected to establish the sepsis model.At 30 min after LPS or normal saline intraperitoneal injection, esketamine 10 mg/kg was intraperitoneally injected, and administration was repeated 12 h later in group SE and group CE.At 24 h after LPS injection, left ventricular ejection fraction (LVEF) was measured (using echocardiography), and serum cardiac troponin I (cTnI), brain natriuretic peptide (BNP), lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), tumor necrosis factor alpha (TNF-α) and high mobility group box-1 (HMGB1) concentrations were determined (by enzyme linked immunosorbent assay). Myocardial tissues were obtained for examination of pathological changes (by hematoxylin-eosin staining) and for determination of expression of Nrf2, HO-1 and transcription factor Bach 1 (BTB-CNC allogeneic 1). Results:Compared with group C, LVEF was significantly decreased, concentrations of cTnI, BNP, LDH, CK-MB, TNF-α and HMGB1 in serum were increased, expression of Nrf2 and HO-1 was down-regulated, and expression of Bach 1 was up-regulated ( P<0.05), and the significant pathological changes of myocardial tissues were found in S and SE groups.No significant change was found in the parameters mentioned above in group CE ( P>0.05). Compared with group S, LVEF was significantly increased, concentrations of cTnI, BNP, LDH, CK-MB, TNF-α and HMGB1 in serum were decreased, expression of Nrf2 and HO-1 was up-regulated, and expression of Bach 1 was down-regulated ( P<0.05), and the pathological changes of myocardium were significantly attenuated in group SE. Conclusion:Esketamine can reduce myocardial injury, and the mechanism may be related to activating Nrf2/HO-1 signaling pathway in septic rats.
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Objective:To evaluate the role of tumour necrosis factor-α-induced protein 8-like 2 (TIPE2) in the acute lung injury (ALI) induced by endotoxin in mice.Methods:Forty SPF healthy adult male BALB/c mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=10 each) using a random number table method: vehicle plasmid group (VP group), vehicle plasmid plus ALI group (VP+ ALI group), TIPE2 adeno-associated virus overexpression group (T group) and TIPE2 adeno-associated virus overexpression plus ALI group (T+ ALI group). The mice in VP and VP+ ALI groups were injected with empty adeno-associated virus, while the mice in T and T+ ALI groups were intratracheally given adeno-associated virus carrying TIPE interference sequence.Three weeks later, the model of endotoxin-induced ALI was established.Lipopolysaccharide (LPS) 5 mg/kg was intratracheally given in VP+ ALI and T+ ALI groups, and the equal volume of phosphate buffered saline (PBS) was given in VP and T groups.Blood samples were obtained from the abdominal aorta at 24 h after injection of LPS for blood gas analysis, oxygenation index (OI) was calculated, and tumor necrosis factor-alpha (TNF-α) in serum were detected by enzyme-linked immunosorbent assay.The animals were then sacrificed, and lung tissues were removed for examination of pathological changes which were scored after haematoxylin and eosin staining, for calculation of the wet/dry weight ratio (W/D ratio) and for determination of myeloperoxidase (MPO) activity and the expression of TIPE2, phosphorylated c-Jun N-terminal kinase (p-JNK) and nuclear factor kappa B(NF-κB) (by Western blot). Results:Compared with VP group, the lung injury score, W/D ratio, MPO activity and concentration of serum TNF-α were significantly increased, PaO 2 and OI were decreased, expression of TIPE2 was down-regulated and expression of p-JNK and NF-κB was up-regulated in VP+ ALI group ( P<0.05). Compared with VP+ ALI group, the lung injury score, W/D ratio, MPO activity and concentration of serum TNF-α were significantly decreased, PaO 2 and OI were increased, expression of TIPE2 was up-regulated and expression of p-JNK and NF-κB was down-regulated in T+ ALI group ( P<0.05). Conclusion:The down-regulation of TIPE2 expression is involved in the process of ALI induced by endotoxin in mice.
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Objective:To evaluate the effects of esketamine on pyrolysis in lung tissues of rats with endotoxin-induced acute lung injury (ALI).Methods:SPF healthy adult male Sprague-Dawley rats, weighing 200-220 g, aged 8 weeks, were divided into 3 groups ( n=10 each) using a random number table method: control group (group C), endotoxin-induced ALI group (group ALI) and esketamine group (group E). Lipopolysaccharide (LPS) 10 mg/kg was intraperitoneally injected to establish the model of endotoxin-induced ALI model.The equal volume of 0.9% sodium chloride injection was intraperitoneally injected in group C. Esketamine 10 mg/kg was intraperitoneally injected at 30 min of injection of LPS in group E. Lung tissues were removed after blood samples were collected from hearts at 24 h after injection of LPS for determination of concentrations of serum interleukin-1beta (IL-1β) and IL-8 (by enzyme-linked immunosorbent assay), the wet/dry weight ratio (W/D ratio), activities of myeloperoxidase (MPO) (by colorimetric assay) and the expression of nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3), caspase-1 and gasdermin D (GSDMD) (by Western blot) and for examination of pathological changes which were scored after haematoxylin and eosin staining and ultrastructure (using an electron microscope). Results:Compared with group C, the lung injury score, W/D ratio, MPO activity, expression of NLRP3, caspase-1 and GSDMD and concentrations of IL-1β and IL-18 in serum were significantly increased in ALI and E groups ( P<0.05). Compared with group ALI, the lung injury score, W/D ratio, MPO activity, expression of NLRP3, caspase-1 and GSDMD and concentrations of IL-1β and IL-18 in serum were significantly decreased in group E ( P<0.05). Conclusion:The mechanism by which esketamine reduces endotoxin-induced ALI is related with inhibition of pyrolysis in lung tissues of rats.
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Objective Observed by ultrasound,this study investigated anatomical characters of median nerve affecting the minimal current intensity of percutaneous electrical nerve stimulation (PNS).Methods Forty healthy adult volunteers were enrolled in this prospective observational stud-y.PNS was performed with a stimulating pen in 2 Hz,0.2 ms,3 mA probe mode for cubits the me-dian nerve localization.Stimulation current was adjusted according to the motor response and the min-imal current intensity at which the motor response was obtained was recorded.There after,the medi-an nerve was observed with ultrasound imaging at the location point.Then,the depth,diameter,area and circumference of the nerve were determined.Results The minimal current intensity was (1.9 ± 0.6)mA and the depth of nerve was (6.1±1.7)mm.The linear regression equation between the mini-mal current intensity and the depth of nerve is:Y (nerve depth,cm)=0.359 +0.135X1 (minimum current intensity,mA),the determination coefficient R2 =0.25 1 (P <0.01).Conclusion The stimu-lation threshold of PNS localization the median nerve was correlated to the depth of nerve,which sug-gests that PNS not only can determine the position of the peripheral nerve,but also can help predict the depth of the peripheral nerve according to the minimum stimulus current.