الملخص
Objective To investigate the effect of rats'injuries and its mechanism caused by specific dose of radiation combined with decompression exposure.Methods 81 male SD rats were randomly divided into control group(n=9),radiation group(n=18),radiation+low-load decompression group(n=18),radiation+medium-load decompression group(n=18),and radiation+high-load decompression group(n=18).In addition to control group,the rats were irradiated with 60Co γ rays at 4 Gy and then underwent rapid escape experiments.The high-pressure exposure schemes were to stay underwater 57 m for 30 min,45 min or 60 min and reduce to normal pressure within(30±5)s,respectively.The high-pressure exposure was not carried out in radiation group.The behavior and death of rats in each group were observed 0.5 h after leaving the cabin.Blood(abdominal aorta)and lung tissues were collected at 3 h and 72 h,respectively.The changes of lung wet-dry weight ratio(W/D),lung pathology and serum levels of interleukin(IL)-1β,IL-6,tumor necrosis factor-α(TNF-α),superoxide dismutase(SOD),malondialdehyde(MDA),nitric oxide(NO),intercellular adhesion molecule-1(ICAM-1)and thromboxane B2(TXB2)were analyzed.Results Compared with control group and radiation group,radiation+low-load decompression group showed no significant difference in the injury and death rate of rats(P＞0.05),while radiation+medium-load decompression group and radiation+high-load decompression group showed significantly increase of the injury and death rate of rats(P＜0.05).Compared with control group,other groups showed no significant change in pulmonary W/D at 3 h(P＞0.05),and increased at 72 h(P＜0.05).HE staining showed that compared with control group,radiation group showed mild lung interstitial edema,while radiation+low-load decompression group showed obvious pulmonary tissue edema and a small number of red blood cells exudated in the alveolar cavity.The edema,congestion and inflammatory cell infiltration of lung tissue were more serious in radiation+medium-load decompression group and radiation+high-load decompression group.Compared with control group and radiation group,all radiation+decompression groups showed an increase in serum levels of IL-1β,IL-6,TNF-α,MDA,NO,ICAM-1 and TXB2(P＜0.05),and a decrease in SOD activity(P＜0.05).Compared with radiation+low-load decompression group,radiation+medium-load decompression group and radiation+high-load decompression group showed increase in serum levels of IL-1β,IL-6,MDA,ICAM-1 and TXB2(P＜0.05),and decrease in activity of SOD(P＜0.05).Except for control group,serum levels of IL-1β,IL-6,TNF-α,MDA,NO,ICAM-1 and TXB2 were decreased at 72 h compared with 3 h(P＜0.05),and SOD activity was increased at 72 h in all groups(P＜0.05).Conclusions High-load decompression can increase the injury and death rate of rats exposed to radiation and high pressure.The potential mechanism of the combined injury effect of radiation and decompression was related to inflammation,immune stress,oxidative damage,vasomotor activity and coagulation mechanism.
الملخص
Objective To explore the potential mechanisms underlying the prominent efficiency of hyperbaric oxygen therapy (HBOT) in the treatment of severe coronavirus disease 2019 (COVID-19) patients. Methods Five COVID-19 patients, aged from 24 to 69 years old, received HBOT after routine therapies failed to stop the deterioration and progressive hypoxemia in General Hospital of the Yangtze River Shipping. The procedure of HBOT was as follows: compressed to 2.0 ATA (0.1 MPa gauge pressure, patient 1) or 1.6 ATA (0.06 MPa gauge pressure, patient 2-5) at a constant rate for 15 min, maintained for 90 min (first treatment) or 60 min (subsequent treatment), then decompressed to normal pressure for 20 min, once a day; the patients inhaled oxygen with the mask of Built-in-Breathing System continuously; and HBOT was ended when the daily mean pulse oxygen saturation (SpO2) in wards was above 95% for two days. The symptoms, respiratory rate (RR), SpO2, arterial blood gas analysis, blood routine, coagulation function, high-sensitivity C-reactive protein (hs-CRP) and chest computed tomography (CT) were collected. Paired t test was used to compare each index before and after treatment. Results After the first HBOT, the symptoms and signs of the five patients began to improve. Supine breathlessness disappeared after HBOT for four times, and digestive tract symptoms completely disappeared and only mild chest pain and breathlessness at rest and in motion remained after HBOT for five times. After finishing HBOT, the RR of the patients was significanlty lower than that before HBOT ([20.80±2.28] min-1 vs [27.20±5.40] min-1, P0.05). Before HBOT, the arterial partial pressure of carbon dioxide (PaCO2) of the patients was (31.48±3.40) mmHg (1 mmHg=0.133 kPa), which was lower than the normal range (35-45 mmHg). After finishing HBOT, arterial partial pressure of oxygen ([130.20±18.58] mmHg), arterial oxygen saturation ([98.40±0.55]%), lymphocyte proportion (0.207 8±0.074 2) and lymphocyte count ([1.09±0.24]×109/L) were significantly higher than those before HBOT ([61.60±15.24] mmHg, [73.20±6.43]%, 0.094 6±0.062 1, and [0.61± 0.35]×109/L), while the levels of fibrinogen ([2.97±0.27] g/L) and hs-CRP ([7.76±6.95] mg/L) were significantly lower than those before HBOT ([4.45±0.94] g/L and [30.36±1.27] mg/L) (all P0.05). All the five patients had typical lung CT imaging changes of severe COVID-19 before HBOT, which were improved after HBOT. Conclusion Systemic hypoxia induced by persistent hypoxemia may be the main reason for the deterioration of severe COVID-19. The respiratory dysfunction of COVID-19 is mainly alveolar gas exchange dysfunction. HBOT may be the best way to correct the progressive hypoxemia which can not be controlled by atmospheric oxygen supply in severe COVID-19 patients. HBOT can provide enough oxygen supply for the continuous hypoxia tissues, and is beneficial to the recovery of immune function, circulatory function and stress level, so as to improve the condition of patients.
الملخص
Objective: To observe the change of microglia activity after fast decompressing and/or hyperbaric oxygenation (HBO)-induced central nervous system (CNS) damage, so as to study the role of microglia in CNS dysbaric injury and the effects of HBO on microglia. Methods: Rats were randomly divided into the following groups: normal control, safe decompressing, fast decompressing (FD) injured, and HBO treated groups. Rat models of dysbaric injury were established by FD; 6 h later the rat models were subjected to HBO treatment. The activated microglia were detected by FITC-linked Isolectin B4; TNF-α and TNF-α converting enzyme (TACE) positive cells were detected immunohistochernically; and neural apoptosis was detected by TUNEL assay. TNF-α contents in CNS tissue were determined by ELISA and the bioactivity of sTNF-α in cerebrospinal fluid (CSF) were determined by L929 cell cytotoxicity bioassay. Results: 1134 positive microglia appeared in rats' CNS 6 h after FD treatment, peaked after 24 h, and declined thereafter. The activated microglia had morphological changes. Cell apoptosis indices of CNS reached its peak 48 h after FD treatment. Activated microglia and apoptotic neurons had similar distribution. TNF-α was detected in the brain and spinal cord 6 h after FD, significantly increased after 24 h, and peaked after 48 h. The content of TNF-α was positively correlated with IB4 positive cells and apoptosis index (P<0.05). TNF-α bioactivity in CSF of FD group had a similar change to TNF-α content in CNS tissue. The IHC results showed that, TNF-α and TACE positive cells had the same morphology and distribution to those of IB4 positive cells. HBO treatment significantly decreased IB4 positive cells after 24 h, 48 h, and 72 h; reduced TNF-α content in CNS tissues and TNF-α cytotoxicity in CSF; and decreased the apoptosis index after 48 h and 72 h. Conclusion: Microglial cells are quickly activated after dysbaric-induced injury of CNS. The activated microglia play a role in secondary injury through increasing TNF-α and TACE expression. HBO therapy can protect the neurons through depressing the activation and proliferation of microglia and reducing secretion of neurotoxin.