Zheng J

Hyperbaric Oxygen Preconditioning Induces Tolerance against Oxidative Injury and Oxygen-Glucose Deprivation by Up-Regulating Heat Shock Protein 32 in Rat Spinal Neurons

Objective Hyperbaric oxygen (HBO) preconditioning (HBO-PC) has been testified to have protective effects on spinal cord injury (SCI). However, the mechanisms remain enigmatic. The present study aimed to explore the effects of HBO-PC on primary rat spinal neurons against oxidative injury and oxygen-glucose deprivation (OGD) and the relationship with heat shock proteins (HSPs). Methods Primary rat spinal neurons after 7 days of culture were used in this study. HSPs were detected in rat spinal neurons following a single exposure to HBO at different time points by Western blot. Using lactate dehydrogenase release assay and cell counting kit-8 assay, the injuries induced by hydrogen peroxide (H2O2) insult or OGD were determined and compared among neurons treated with HBO-PC with or without HSP inhibitors. Results The results of Western blot showed that HSP27, HSP70 and HSP90 have a slight but not significant increase in primary neurons following HBO exposure. However, HSP32 expression significantly increased and reached highest at 12 h following HBO exposure. HBO-PC significantly increased the cell viability and decreased the medium lactate dehydrogenase content in cultures treated with H2O2 or OGD. Pretreatment with zinc protoporphyrin IX, a specific inhibitor of HSP32, significantly blocked the protective effects of HBO-PC. Conclusions These results suggest that HBO-PC could protect rat spinal neurons in vitro against oxidative injury and OGD mostly by up-regulating of HSP32 expression.

Changes in angiotensin II and angiotensin-converting enzyme of different tissues after prolonged hyperoxia exposure

Current study findings concerning changes in the renin-angiotensin system (RAS) in cases of hyperoxic acute lung injury (HALI) have shown conflicting results. This study aimed to detect the angiotensin II (Ang II) and angiotensin-converting enzyme (ACE) in a rat HALI model. Healthy male Sprague-Dawley rats were randomly assigned into three groups: the control group, HALI group and hyperbaric oxygen preconditioning (HBO₂-PC) group. HALI was induced by exposure to pure oxygen at 250 kPa for six hours. In the HBO₂-PC group, rats were exposed to oxygen at 250 kPa for 60 minutes twice daily for two consecutive days; HALI was induced at 24 hours after the last oxygen exposure.=After HALI, the lung, spleen and liver were harvested for HE staining and pathological examination. At one hour and 18 hours after HALI, the blood, liver, lung and spleen were collected for the detection of Ang II and ACE contents by enzyme-linked immunosorbent assay. Pathological examination showed the lung was significantly damaged and characteristics of HALI were observed, but there were no significant pathological changes in the liver and spleen. After HALI, Ang II and ACE contents of different tissues increased progressively over time, but the HBO₂-PC group showed reductions in the Ang II and ACE contents to a certain extent, especially at 18 hours after injury. These findings suggest prolonged hyperoxia exposure may activate the RAS, which may be associated with the pathogenesis of HALI. HBO₂-PC has a limited capability to inhibit RAS activation.

SC5b-9-Induced Pulmonary Microvascular Endothelial Hyperpermeability Participates in Ventilator-Induced Lung Injury

Mechanical ventilation with large tidal volumes can increase lung alveolar permeability and initiate inflammatory responses, termed ventilator-induced lung injury (VILI). VILI is characterized by an influx of inflammatory cells, increased pulmonary permeability, and endothelial and epithelial cell death. But the underlying molecular mechanisms that regulate VILI remain unclear. The purpose of this study was to investigate the mechanisms that regulate pulmonary endothelial barrier in an animal model of VILI. These data suggest that SC5b-9, as the production of the complement activation, causes increase in rat pulmonary microvascular permeability by inducing activation of RhoA and subsequent phosphorylation of myosin light chain and contraction of endothelial cells, resulting in gap formation. In general, the complement-mediated increase in pulmonary microvascular permeability may participate in VILI.

Nitric oxide and hyperoxic acute lung injury

Hyperoxic acute lung injury (HALI) refers to the damage to the lungs secondary to exposure to elevated oxygen partial pressure. HALI has been a concern in clinical practice with the development of deep diving and the use of normobaric as well as hyperbaric oxygen in clinical practice. Although the pathogenesis of HALI has been extensively studied, the findings are still controversial. Nitric oxide (NO) is an intercellular messenger and has been considered as a signaling molecule involved in many physiological and pathological processes. Although the role of NO in the occurrence and development of pulmonary diseases including HALI has been extensively studied, the findings on the role of NO in HALI are conflicting. Moreover, inhalation of NO has been approved as a therapeutic strategy for several diseases. In this paper, we briefly summarize the role of NO in the pathogenesis of HALI and the therapeutic potential of inhaled NO in HALI.

Oridonin protects the lung against hyperoxia-induced injury in a mouse model

Hyperoxic acute lung injury (HALI) is caused by prolonged exposure to high oxygen partial pressure. This study was undertaken to investigate the protective effects of oridonin on HALI in a mouse model. Mice were randomly divided into three groups: the control group, HALI group and oridonin (ORI) group. HALI was induced by exposing mice to pure oxygen at 2.5 atmospheres absolute (ATA) for six hours in the HALI and ORI groups. In the ORI group, mice were intraperitoneally injected with ORI at 10 mg/kg twice daily after hyperoxic exposure. Animals were sacrificed 24 hours after the hyperoxia exposure, followed by bronchoalveolar lavage fluid (BALF). Lungs were then collected. Each lung was processed for HE staining and detection of wet-to-dry weight ratio. The lactate dehydrogenase (LDH) activity and protein content of BALF were determined, and the contents of malonaldehyde (MDA), glutathione (GSH), tumor necrosis factor alpha (TNF-?) and interleukin-10 (IL-10) in the lung were measured. Our results showed prolonged exposure to hyperoxia significantly damaged the lung, caused lung edema, increased MDA and TNF-?, and reduced GSH and IL-10 in the lung. However, post-exposure treatment with oridonin was able to improve lung pathology, attenuate lung edema, reduce MDA and TNF-?, and increase GSH and IL-10 in the lung. These findings suggest that oridonin can protect the lung against hyperoxia-induced injury in mice.