Hepatoprotective effects of sevoflurane against hepatic ischemia-reperfusion injury by regulating microRNA-124-3p-mediated TRAF3/CREB axis.

The purpose of the present study is to define the role of sevoflurane (SEV) in hepatic ischemia-reperfusion (I/R) injury as well as its underlying mechanism. Initially, hepatic I/R animal models and I/R hepatocyte models were established in C57BL/6 mice and normal mouse hepatocytes (BNL CL.2) after SEV preconditioning, respectively, followed by detection of microRNA-124-3p (miR-124-3p), TRAF3, and CREB expression by RT-qPCR and Western blot analysis. In addition, miR-124-3p, TRAF3 and CREB expression in hepatocytes was altered to identify their roles in modulating the levels of glutathione transferase (GST), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and inflammation-related factors and hepatocyte apoptosis by ELISA and flow cytometry respectively. The effects of SEV on the miR-124-3p/TRAF3/CREB axis were also verified in vitro and in vivo. IP assay was performed to verify the effect of TRAF3 on CREB ubiquitination in BNL CL.2 cells, and the cycloheximide (CHX) intervention experiment to detect the stability of CREB protein. SEV augmented the miR-124-3p expression in I/R animal and cell models. Moreover, SEV was observed to suppress I/R-induced liver damage, GST, ALT, and AST levels, hepatocyte apoptosis and inflammation. Overexpression of miR-124-3p resulted in alleviation of hepatic I/R injury, which was countered by TRAF3 overexpression. miR-124-3p targeted TRAF3, while TRAF3 promoted CREB ubiquitination and reduced protein stability of CREB. SEV could impede I/R-induced liver damage, GST, ALT, and AST levels, hepatocyte apoptosis and inflammation via mediation of the miR-124-3p/TRAF3/CREB axis in vitro and in vivo. Collectively, SEV may upregulate miR-124-3p to inhibit TRAF3 expression, thereby reducing the ubiquitination and degradation of CREB, alleviating hepatic I/R injury.

Dexmedetomidine Ameliorates Postoperative Cognitive Dysfunction via the MicroRNA-381-Mediated EGR1/p53 Axis.

Postoperative cognitive dysfunction (POCD; cognitive change associated with anesthesia and surgery) is one of the most serious long-term postoperative complications that occur in elderly patients. Dexmedetomidine (DEX) has been shown to be beneficial for improving outcomes of postoperative cognitive function. However, the exact mechanism underlying this role requires is yet to be found. The present study aims to determine the pathways involved in the protective effects of DEX against POCD in C57BL/6 J aged mice. DEX was administered after POCD modeling in C57BL/6 J aged mice. The cognitive function was evaluated after DEX treatment using novel object recognition, open field, and Y-maze tests. We also assessed its effects on neuron apoptosis and production of TNF-α and IL-1ß in mouse brain tissues as well as expression levels of DNA damage-related proteins p53, p21, and γH2AX. Interactions between early growth response 1 (EGR1) and p53, microRNA (miR)-381, and EGR1 were identified by ChIP and luciferase reporter assays, and gain- and loss-of-function experiments were performed to confirm the involvement of their interaction in POCD. DEX administration attenuated hippocampal neuron apoptosis, neuroinflammation, DNA damage, and cognitive impairment in aged mice. miR-381 targeted EGR1 and disrupted its interaction with p53, leading to a decline in hippocampal neuron apoptosis, DNA damage, neuroinflammation, and cognitive impairment. Furthermore, DEX administration resulted in the enhancement of miR-381 expression and the subsequent inhibition of EGR1/p53 to protect against cognitive impairment in aged mice. Overall, these results indicate that DEX may have a potential neuroprotective effect against POCD via the miR-381/EGR1/p53 signaling, shedding light on the mechanisms involved in neuroprotection in POCD.

Protective effects of bone marrow-derived endothelial progenitor cells and Houttuynia cordata in lipopolysaccharide-induced acute lung injury in rats.

BACKGROUND/AIMS: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a serious health problem, and an effective treatment is needed for use in the clinical setting. METHODS: In this study, we first constructed ALI models in Adult Sprague-Dawley rats. We then used an herbal medicine, Houttuynia cordata (HC), to enhance the effect of endothelial progenitor cells (EPCs) on ALI. RESULTS: (1) HC improved the therapeutic effects of EPCs on lipopolysachharide-induced ALI in the rat model; (2) HC down-regulated the anti-inflammatory response by suppressing inflammatory cytokines; (3) the combination of EPC and HC reduced expression of iNOS and ET-1 and subsequently prevented lung injury. CONCLUSION: Combined EPC and HC therapy was more effective than either therapy alone. EPC and HC could be used in the clinical treatment of ALI.

Autologous transplantation of adipose-derived stromal cells ameliorates ventilator-induced lung injury in rats.

BACKGROUND: Adipose-derived stromal cells (ADSCs) are a good alternative to multipotent stem cells for regenerative medicine. Low tidal volume (LVT) has proved to be an effective ventilation strategy. However, it is not known if ADSCs and LVT can protect against ventilator-induced lung injury (VILI). This study was aimed to determine the potential of ADSCs and LVT to repair following VILI and to elucidate the mechanisms responsible for this section. METHODS: A total of 72 rats were randomly assigned into group I (sham group, n=18), group II (1 h of high tidal volume-ventilated (HVT) 40 mL/kg to peak airway pressures of approximately 35 cm H2O and 100% oxygen, n=18), group III (1 h of HVT followed by 6 h LVT 6 mL/kg to peak airway pressures of approximately 6 cm H2O and 100% oxygen, n=18) and group IV (1 h of HVT followed by intravenous injection of 5 × 106 ADSCs, n=18). All animals were sacrificed 7 after the experiments lasted for 7 hours. Bronchoalveolar lavage fluid (BALF) was collected and lungs were harvested for analysis. RESULTS: High tidal volume-ventilated (HVT) rats exhibited typical VILI features compared with sham rats. Lung edema, histological lung injury index, concentrations of total protein, total cell counts, number of neutrophils in bronchoalveolar lavage fluid (BALF), tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, IL-10 and transforming growth factor-ß1 in BALF were significantly increased in HVT rats. Additionally, gene and protein levels of Na+ channel subunits, Na-K-ATPase pump activity and alveolar fluid clearance were significantly decreased in HVT rats. All these indices of VILI were significantly improved in rats treated with ADSCs. However, compared with ADSCs treatment, LVT strategy had little therapeutic effect in the present study. CONCLUSION: These results may provide valuable insights into the effects of ADSCs in acute lung injury.

Protective effects of penehyclidine hydrochloride on liver injury in a rat cardiopulmonary bypass model.

BACKGROUND AND OBJECTIVE: Hepatic injury after cardiac surgery is considered to be a consequence of cardiopulmonary bypass (CPB). The aim of this study was to test the hypothesis that penehyclidine hydrochloride (PHC) could attenuate hepatic injury using a rat CPB model. METHODS: Male Sprague-Dawley rats were randomly divided into six groups (eight per group), including sham-operated control, sham low-dose PHC control (0.6 mg kg), sham high-dose PHC control (2.0 mg kg), vehicle control, low-dose PHC (0.6 mg kg) and high-dose PHC (2.0 mg kg)-treated groups. Blood samples were collected from the femoral artery at the cessation of CPB and the serum levels of the liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), were determined. The ultrastructure of liver tissue was also examined under an electron microscope. RESULTS: In the sham-operated groups, high-dose PHC and low-dose PHC had no significant impact on the levels of respiratory rate, heart rate, blood pressure, ECG, ALT or AST. Compared with the sham group, the serum levels of ALT and AST were increased significantly in the surgical groups. PHC alleviated all the biochemical and histopathological changes in a dose-dependent manner. The ALT and AST levels in the high-dose PHC-treated groups were significantly lower than those in the vehicle control group. CONCLUSION: Treatment with penehyclidine hydrochloride could improve liver function during CPB.