ObjectiveTo investigate the protective effect of atomized inhalation of nano-luteolin preparation on acute lung injury caused by extracorporeal circulation, and to explore the anti-inflammatory mechanism of luteolin, so as to provide study basis for clinical application.MethodsThirty male SD rats aged 5-6 weeks and weighting 160-190 g, were randomly divided into a preoperative baseline (BL) group, arteriovenous partial diversion (ECC) group, luteolin atomization pretreatment for 1 h group, 2 h group, and 3 h group by random number method, with 6 rats in each group. In the BL group, lung tissue samples were collected directly without any treatment. The ECC group received mechanical ventilation, and the whole body was heparinized after the jugular arteriovenous intubation. The flow was transferred for 30 minutes, followed by observation for 60 minutes, then lung tissue samples were collected. Subjects in the 1 h, 2 h and 3 h groups were placed in a small animal atomizer 1 h, 2 h and 3 h before flow transfer respectively, and the subsequent operation was the same as that in the ECC group. The inflammatory level of lung tissue was detected to evaluate the degree of pathological injury of lung tissue. Western blotting (WB) was used to detect the contents of p65, IKKα, IKKβ and IKKγ in the cytoplasm of lung tissue samples of each group.ResultsCompared with the ECC group, the levels of IL-6 and TNF-α in lung tissues and the degree of pathological injury in the 1 h, 2 h and 3 h groups decreased, and the difference between the 3 h group and the ECC group was statistically different (P<0.05). WB results showed that compared with the ECC group, the levels of p65 in lung tissue of the 1 h, 2 h and 3 h groups decreased; the levels of IKKβ in the lung tissue increased in the 1 h, 2 h and 3 h groups, and the difference of the 3 h group was statistically different from the ECC group (P<0.05).ConclusionLuteolin has a protective effect on acute lung injury induced by ECC, and atomization 3 h in advance has the best protective effect on lung. The mechanism plays a protective role in ECC-induced acute lung injury, may be through inhibition of IKKβ phosphorylation, thereby inhibiting the classical NF-κB signaling pathway.
Acute lung injury is one of the common and serious complications of acute aortic dissection, and it greatly affects the recovery of patients. Old age, overweight, hypoxemia, smoking history, hypotension, extensive involvement of dissection and pleural effusion are possible risk factors for the acute lung injury before operation. In addition, deep hypothermia circulatory arrest and blood product infusion can further aggravate the acute lung injury during operation. In this paper, researches on risk factors, prediction model, prevention and treatment of acute aortic dissection with acute lung injury were reviewed, in order to provide assistance for clinical diagnosis and treatment.
ObjectiveTo investigate the effect of different administration methods of tranexamic acid on postoperative pulmonary inflammation response during cardiopulmonary bypass (CPB).MethodsA total of 64 SD rats were included in the study. They were randomly divided into eight different groups. CPB model was established for the operation groups. The rats in the operation groups were given tranexamic acid at low (25 mg/kg), medium (50 mg/kg) or high (100 mg/kg) concentrations before or after the CPB. Blood cells count and coagulation function were assessed 1 hour after surgery. The concentration of interleukin (IL)-1β、IL-6 and tumor necrosis factor (TNF)-α in blood and lung lavage fluid were measured. The infiltration of inflammatory cells in lungs was observed by hematoxylin-eosin (HE) staining.ResultsThe concentration of inflammatory cells in the operation groups was higher than that in the control group (P<0.05). The use of tranexamic acid inhibited the increase of IL-6 and TNF-α in whole blood and lung lavage fluid due to CPB (P<0.05), but there was no significant difference among the experimental groups (P>0.05). Tranexamic acid could reduce the exudation of inflammatory cells in the lungs.ConclusionThe use of tranexamic acid can effectively reduce the release of inflammatory factors and reduce acute lung injury caused by CPB in rat models. But simply increasing the dose or changing the timing of administration is not more effective in reducing the intensity of the inflammatory response.
Acute lung injury is a kind of common complication after cardiopulmonary bypass. Acute lung injury is attributed to the ischemia-reperfusion injury and systemic inflammatory response syndrome. Several factors common in cardiac surgery with cardiopulmonary bypass may worsen the risk for acute lung injury including atelectasis, transfusion requirement, older age, heart failure, emergency surgery and prolonged duration of bypass. Targets for prevention of acute lung injury include mechanical, surgical and anesthetic interventions that aim to reduce the contact activation, systemic inflammatory response, leukocyte sequestration and hemodilution associated with cardiopulmonary bypass. We aim to review the etiology, risk factors and lung protective strategies for acute lung injury after cardiopulmonary bypass.
Objective To explore the effect of early short-term use of low-dose steroids on early acute lung injury (EALI) after video-assisted thoracoscopic lobectomy. Methods Patients who underwent video-assisted thoracoscopic lobectomy in our department from January 2019 to January 2022 were selected for this retrospective cohort study. They were divided into an early steroid treatment group and a control group based on whether steroids were used in the early postoperative period. In the early steroid treatment group, in addition to routine postoperative treatment, low-dose methylprednisolone was administered intravenously, at 80-120 mg/d for 3 consecutive days. In the control group, routine postoperative treatment was given, but no steroids were used in the first 3 days. A chest computed tomography (CT) scan was performed on postoperative day (POD) 1, and POD3 or POD4 to assess lung injury. Chest CT scores, the EALI incidence, the length of hospital stay, and the incidence of poor incision healing were recorded. ResultsA total of 521 patients were included, consisting of 255 males and 266 females, aged 11-80 years. There were 203 patients in the early steroid treatment group and 318 patients in the control group. On POD1, the incidence of EALI was 16.0% in the control group and 13.8% in the steroid group, with no significant difference between the two groups (P>0.05). There was also no significant difference in the CT scores of patients with EALI in the two groups (P>0.05). On POD3/4, the incidence of EALI was 33.6% in the control group and 22.7% in the steroid group, showing a significant difference (P=0.007). When comparing the CT scores of patients with EALI in both groups, the scores were lower in the steroid group, but the difference was not significant (P>0.05). The overall incidence of EALI on POD1-4 was 37.4% in the control group and 26.1% in the steroid group, showing a significant difference (P=0.007). Of these, 28.9% of patients in the control group showed radiological progression, which means new EALI occurred or existing EALI progressed, while the progression rate was 14.8% in the steroid group (P<0.001). The length of hospital stay was significantly shorter in the steroid group compared to the control group (P<0.001), but the incidence of poor incision healing was not (P>0.05). Conclusion Early use of corticosteroids cannot reduce the incidence and severity of EALI on POD1, but it can reduce the incidence of EALI on POD3/4 and decrease the risk of radiological progression, and also lower the overall risk of EALI after surgery, without extended postoperative hospital stays or increased incidence of poor incision healing. Therefore, early postoperative use of low-dose corticosteroids can help to inhibit the occurrence and progression of EALI. It is suggested to use as early as possible especially in patients with high risks of postoperative EALI.
急性肺損傷（ALI）和急性呼吸窘迫綜合征（ARDS）是指由心源性以外的各種肺內外致病因素所導致的急性進行性缺氧性呼吸衰竭，它們具有性質相同的病理生理改變，嚴重的ALI或ALI的最終嚴重階段被定義為ARDS，臨床表現以呼吸窘迫、頑固性低氧血癥和非心源性肺水腫為特征，采用常規的治療難以糾正其低氧血癥，死亡率高達60%。目前，有關ALI/ARDS的研究取得較多進展，其中，能有效評估ALI病情和預測死亡率的臨床參數和生化指標一直是研究熱點。
Objective To investigate the effect of non-coding RNA activated by DNA damage (NORAD) on acute lung injury (ALI) in septic rats by regulating the miR-155-5p/TLR6 molecular axis. Methods The rats were randomly divided into control group, model group, low NORAD expression no-load group (LV-sh-NC), low NORAD expression group (LV-sh-NORAD), low NORAD expression +miR-155-5p low expression no-load group (LV-sh-NORAD+NC antagomir), NORAD low expression +miR-155-5p low expression group (LV-sh-NORAD+miR-155-5p antagomir). ELISA kits were applied to detect interleukin (IL)-8, IL-1β, and tumor necrosis factor-α (TNF-α) levels; quantitative real-time polymerase chain reaction was applied to detect the expression of NORAD, miR-155-5p, and Toll-like receptor 6 (TLR6) genes in lung tissue of rats in each group. The ratio of wet weight to dry weight (W/D) of lung tissue was measured. The pathological changes of lung tissue were observed by hematoxylin-eosin staining, and apoptosis in lung tissue cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling. Western blot was applied to detect the expressions of TLR6, Bax, Bcl-2, and cleaved cysteinyl aspartate specific proteinase 3 caspase-3) proteins in cells. Dual luciferase reporter gene experiment was applied to verify the relationship between miR-155-5p and NORAD and TLR6. Results Compared with the control group, the lung tissue of rats in the model group and LV-sh-NC group was obviously damaged, the levels of serum IL-1β, TNF-α, IL-8, expression of NORAD and TLR6 mRNA in lung tissue, W/D ratio, apoptosis rate, expression of TLR6, Bax, and Cleaved-caspase-3 proteins were obviously increased, the expression of miR-155-5p and Bcl-2 proteins in lung tissue was obviously reduced (P<0.05). Down-regulation of NORAD expression could reduce lung tissue injury, serum IL-1β, TNF-α, IL-8 levels, mRNA expression of NORAD and TLR6 in lung tissue, W/D ratio, apoptosis rate, TLR6, Bax, Cleaved caspase-3 protein expression, and cleaved caspase-3 protein expression. The expression of miR-155-5p and Bcl-2 protein in lung tissue were significantly increased (P<0.05). Down-regulating the expression of miR-155-5p could reduce the improvement effect of negatively regulated NORAD on sepsis ALI rats (P<0.05). Conclusion Interference with NORAD can alleviate lung injury in ALI rats by regulating the miR-155-5p/TLR6 molecular axis.
Objective To investigate whether p38 mitogen activated protein kinase (p38MAPK) inhibitor can reduce acute lung injury (ALI) caused by lipopolysaccharide (LPS) by regulating Th17/Treg balance. Methods Balb/c mice were randomly divided into a control group, an ALI group and an intervention group. The mice in the control group were injected with phosphate-buffered saline, the mice in the ALI group were intraperitoneally injected with 40 mg/kg LPS, and the mice in the intervention group were injected with SB203580 (0.5 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg) intraperitoneally 1 h prior to the intraperitoneal injection of LPS. All mice were killed on 12 h later respectively. Hematoxylin-eosinstin staining was used to observe the pathological changes of lung tissue, and cell classification, counting, and total protein levels in bronchoalveolar lavage fluid (BALF) were detected. Transcript expression of forkhead box p3 (Foxp3) and retinoic acid receptor-related orphan receptor-γt (RORγt) was detected by real-time polymerase chain reaction. Interleukin (IL)-6, IL-10, IL-17, IL-23 and transforming growth factor-β (TGF-β) in lung tissue and IL-6, tumor necrosis factor-α (TNF-α) in serum were measured by enzyme-linked immunosorbent assay. The Th17 and Treg subset distribution in spleen was determined by ?ow cytometry. Results Histopathological examination showed that LPS induced inflammatory cell infiltration in lung tissue, increased cell count and protein levels in BALF (P<0.05), and increased proportion of neutrophils and monocytes in the ALI mice. SB203580 significantly attenuated tissue injury of the lungs in LPS-induced ALI mice. Serum levels of IL-6 and TNF-α in the ALI group were significantly higher than those in the control group, and inflammatory cytokines were decreased after SB203580 intervention. Compared with the ALI group, the production of inflammatory cytokines associate with Th17, including IL-17, IL-23, RORγt was inhibited, and the production of cytokines associate with Treg, such as IL-10 and Foxp3 in lung tissue was increased in the intervention group in a concentration-dependent manner with SB203580. After SB203580 intervention, Th17/Treg ratio was significantly decreased compared with the LPS group (P<0.05). Conclusion p38MAPK inhibitor can reduce LPS-induced ALI by regulating the imbalance of Treg cells and Th17 cells.
ObjectiveTo investigate the value of chest high-resolution computed tomography (HRCT) score in evaluating the severity of hip fracture-induced early acute lung injury (ALI) in the elderly patients.MethodsThe clinical data of 289 elderly hip fracture patients in Chongqing Traditional Chinese Medicine Hospital from July 2014 to April 2020 were retrospectively analyzed. All patients were divided into two groups, including an ALI group (n=114, 36 males and 78 females at age of 82.94±6.85 years) and a non-ALI group (n=175, 51 males and 124 females at age of 84.42±6.31 years). General information, chest HRCT scores and PaO2/FiO2 were compared between the two groups. Correlation analysis was used to compare the relationship between chest HRCT scores and PaO2/FiO2. Multiple linear stepwise regression analysis was applied to evaluate the effective extent of the diffuse ground glass opacity (DGGO), intense parenchymal opacification (IPO), and reticulation HRCT scores to the overall HRCT scores.ResultsThe DGGO scores, IPO scores, reticulation scores, overall HRCT scores and PaO2/FiO2 were higher in the ALI group than those in the non-ALI group (P<0.001). In the ALI group, correlation analysis showed that DGGO, overall HRCT scores were in significantly negative correlation with PaO2/FiO2 (P<0.001). In addition, the correlation among PaO2/FiO2 and overall HRCT scores was more significant than that of DGGO scores. Multiple stepwise regression analysis indicated that DGGO, IPO, and reticulation scores were independent influencing factors for overall HRCT scores. Among the influencing factors, DGGO scores had the greatest impact, then IPO scores and reticulation scores. The HRCT signs of DGGO, IPO, and reticulation appeared simultaneously had the greatest effects on the overall HRCT scores.ConclusionThe chest HRCT score, which is associated with PaO2/FiO2, also can be used in the severity assessment of elderly patients with early ALI caused by hip fracture.
Lung injury could be classified as acute and chronic injuries, such as acute respiratory distress syndrome and chronic obstructive pulmonary disease. Lung function recovery mainly depends on inflammation adjusting, lung and airway remodeling, endogenous stem cell proliferation and differentiation, and tissue repair. The principles of clinical therapy include inhibition of inflammation, balancing coagulation and fibrinolysis, and protective lung ventilation for acute lung injury; while reduction of hyper-secretion, bronchodilation, adjusting airway mucosal inflammation and immunity, as well as improving airway remodeling for chronic obstructive pulmonary disease. The functional recovery of lung and airway depends on endogenous stem cell proliferation and repair. The purpose of clinical treatment is to provide assistance for lung and airway repair besides pathophysiological improvement.