RESUMO
BACKGROUND: Acute kidney injury is a common clinical comorbidity and early diagnosis is crucial for improving prognosis, but there is still no ideal biomarker for early diagnosis. MATERIAL AND METHODS: miRNA microarray was used for detecting miRNA in kidney subjected to renal ischemia-reperfusion injury 12 h after reperfusion. Real-time PCR was performed to validate the results of microarray. miRNAs in the ischemia group were twice as high as in the sham group. Kidney-enriched miR-10a, miR-192, and miR-194 were detected in rat plasma to screen potential biomarkers for renal ischemia-reperfusion injury. Aberrant expressed miRNA in plasma at 12 h were further detected at 1 h, 2 h, 6 h, 12 h, and 24 h to observe the changing trend of these miRNAs and were compared to blood urea nitrogen and serum creatinine. RESULTS: Thirty-six miRNAs were aberrantly expressed in kidney of rats with renal ischemia-reperfusion injury, among which 15 miRNAs had a 2-fold greater change. Results of real-time PCR were generally in accordance with microarray results. Levels of the 15 miRNAs differentially expressed in injured kidney were not significantly different from those in sham kidney. However, miR-10a, miR-192, and miR-194 were significantly increased in plasma of rats with renal ischemia-reperfusion injury, among which miR-10a was elevated within 1 h after reperfusion, whereas miR-192 and miR-194 were elevated at 6 h after injury. Blood urea nitrogen was increased at 12 h and serum creatinine was increased at 6 h after injury. CONCLUSIONS: Plasma miR-10a, miR-192, and miR-194 were potential biomarkers for renal ischemia reperfusion injury in rats, and miR-10a might be the most promising plasma biomarker for renal injury because of its elevation within 1 h after renal injury, as well as renal specificity.
Assuntos
Injúria Renal Aguda/sangue , Injúria Renal Aguda/diagnóstico , Biomarcadores/sangue , MicroRNAs/sangue , Traumatismo por Reperfusão/sangue , Injúria Renal Aguda/etiologia , Animais , Biologia Computacional , Análise em Microsséries , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Traumatismo por Reperfusão/complicações , Fatores de TempoRESUMO
OBJECTIVES: Opioid-free anaesthesia (OFA) has emerged as a promising approach for mitigating the adverse effects associated with opioids. The objective of this study was to evaluate the impact of OFA on postoperative nausea and vomiting (PONV) following video-assisted thoracic surgery. DESIGN: Single-centre randomised controlled trial. SETTING: Tertiary hospital in Shanghai, China. PARTICIPANTS: Patients undergoing video-assisted thoracic surgery were recruited from September 2021 to June 2022. INTERVENTION: Patients were randomly allocated to OFA or traditional general anaesthesia with a 1:1 allocation ratio. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was the incidence of PONV within 48 hours post-surgery, and the secondary outcomes included PONV severity, postoperative pain, haemodynamic changes during anaesthesia, and length of stay (LOS) in the recovery ward and hospital. RESULTS: A total of 86 and 88 patients were included in the OFA and control groups, respectively. Two patients were excluded because of severe adverse events including extreme bradycardia and epilepsy-like convulsion. The incidence and severity of PONV did not significantly differ between the two groups (29 patients (33.0%) in the control group and 22 patients (25.6%) in the OFA group; relative risk 0.78, 95% CI 0.49 to 1.23; p=0.285). Notably, the OFA approach used was associated with an increase in heart rate (89±17 vs 77±15 beats/min, t-test: p<0.001; U test: p<0.001) and diastolic blood pressure (87±17 vs 80±13 mm Hg, t-test: p=0.003; U test: p=0.004) after trachea intubation. Conversely, the control group exhibited more median hypotensive events per patient (mean 0.5±0.8 vs 1.0±2.0, t-test: p=0.02; median 0 (0-4) vs 0 (0-15), U test: p=0.02) during surgery. Postoperative pain scores, and LOS in the recovery ward and hospital did not significantly differ between the two groups. CONCLUSIONS: Our study findings suggest that the implementation of OFA does not effectively reduce the incidence of PONV following thoracic surgery when compared with traditional total intravenous anaesthesia. The opioid-free strategy used in our study may be associated with severe adverse cardiovascular events. TRIAL REGISTRATION NUMBER: ChiCTR2100050738.
Assuntos
Analgésicos Opioides , Náusea e Vômito Pós-Operatórios , Humanos , Analgésicos Opioides/efeitos adversos , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Cirurgia Torácica Vídeoassistida/efeitos adversos , China/epidemiologia , Anestesia Geral/efeitos adversos , Dor Pós-Operatória/etiologiaRESUMO
BACKGROUND: Senkyunolide I (SEI), a component of a Chinese herb named Ligusticum Chuanxiong hort, which is included in the formulation of Xuebijing Injection, a medication used to treat sepsis in China. Our previous study showed that SEI was protective against sepsis-associated encephalopathy and the present study was performed to investigate the role of SEI in sepsis-induced lung injury in a murine model of cecal ligation and puncture (CLP). METHODS: SEI (36 mg/kg in 200 µl) or vehicle was administered immediately after CLP surgery. The lung injury was assessed 24 h later by histopathological tests, protein concentration in the bronchoalveolar lavage fluid (BALF), neutrophil recruitment in the lung tissue (myeloperoxidase fluorescence, MPO), pro-inflammatory cytokines and oxidative responses. Platelet activation was detected by CD42d/GP5 immunofluorescence and neutrophil extracellular trap (NET) were determined by immunofluorescence assays and enzyme linked immunosorbent assay (ELISA) of MPO-DNA. In vitro experiments were performed to detect the level of MPO-DNA complex released by SEI-treated neutrophils stimulated with phorbol 12-myristate 13-acetate (PMA) or co-cultured with platelets from CLP mice. RESULTS: SEI administration relieved the injury degree in CLP mice according to the histopathological tests (P < 0.05 compared with DMSO + CLP group). Protein level in the BALF and neutrophil infiltration were remarkably reduced by SEI after CLP surgery (P < 0.05 compared with DMSO + CLP group). TNF-α, IL-1ß and IL-6 were decreased in the plasma and lung tissues from CLP mice treated with SEI (P < 0.05 compared with DMSO + CLP group). The phosphorylation of JNK, ERK, p38 and p65 were all inhibited by SEI (P < 0.05 compared with DMSO + CLP group). Immunofluorescence of MPO showed that neutrophil number was significantly lower in SEI treated CLP mice than in vehicle treated CLP mice (P < 0.05). The CD42d/GP5 staining suggested that platelet activation was significantly reduced and the NET level in the lung tissue and plasma was greatly attenuated by SEI treatment (P < 0.05 compared with DMSO + CLP group). In vitro experiments showed that the MPO-DNA level stimulated by PMA was significantly reduced by SEI treatment (P < 0.05 compared with DMSO treatment). Co-culture neutrophils with platelets from CLP mice resulted in higher level of MPO-DNA complex, while SEI partly reversed such effects of platelet on NET formation. CONCLUSIONS: SEI was protective against lung injury induced by CLP in mice. The NET formation was significantly reduced by SEI treatment, which might be involved in the mechanism of the protective effect.
Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Benzofuranos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Animais , Benzofuranos/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Ceco/lesões , Ceco/cirurgia , Citocinas/imunologia , Modelos Animais de Doenças , Armadilhas Extracelulares/efeitos dos fármacos , Armadilhas Extracelulares/imunologia , Ligadura , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/imunologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Sepse/complicações , Sepse/imunologia , Sepse/patologia , Ferimentos Penetrantes/complicações , Ferimentos Penetrantes/tratamento farmacológico , Ferimentos Penetrantes/imunologiaRESUMO
Objective: To screen for miRNAs potentially involved in the pathogenesis of renal ischemia/reperfusion injury. Methods: Renal ischemia reperfusion injury model was established with SD rats. Twelve hours after reperfusion, blood urea nitrogen and serum creatinine were determined and miRNA expression in the kidney was detected using miRNA microarray. Bioinformatics methods were used for a preliminary analysis of potential targets for differentially expressed miRNAs. Results: Blood urea nitrogen and serum creatinine were both elevated 12 h after reperfusion. miRNA microassay showed 36 aberrantly expressed miRNAs, with 15 miRNAs having an expression level higher than 2 folds. Results of real-time PCR were generally in accordance with the microarray results. The elevated miRNAs included miR-290, miR-894, miR-292-5p, miR-327, miR-374, miR-98, miR-352, miR-132, miR-146b and miR-196a; and the down-regulated miRNAs included miR-145, miR-329, miR-375, miR-140 * and miR-29a. Bioinformatics showed that these miRNAs were related to inflammation, cell death and proliferation, angiogensis and fibrosis. Conclusion: Several miRNAs are aberrantly expressed during renal ischemia/ reperfusion injury, which may influence renal injury through regulating inflammation, cell death and proliferation, angiogensis and fibrosis, but the exact mechanism remains to be further investigated.