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.
Objective To investigate the changes in osteoprotegerin (OPG) / receptor activator of nuclear factor-κB ligand (RANKL) ratio in sepsis-associated acute lung injury (SA-ALI) and the role of regulation of this ratio on the inflammatory response in SA-ALI. Methods Eighteen C57BL/6 male mice were randomly divided into sham operation group, cecal ligation and perforation (CLP) group and RANKL group, with 6 mice in each group. Before the experiment, the RANKL group was intraperitoneally injected with 5 μg (0.2 mL) of recombinant RANKL antibody, whereas both the sham operation group and the CLP group were intraperitoneally injected with a volume-matched normal saline. One hour later, the sham operation group underwent only abdominal exploration and repositioning, while the other groups underwent the CLP surgery to induce the SA-ALI model. After 24 h of modelling, all mice were sacrificed and samples were collected. Pathological evaluation of lung tissues was performed by haematoxylin-eosin staining; enzyme-linked immunosorbent assay was used to detect serum concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β; while the mRNA and protein expression of OPG and RANKL, along with their ratio values, were detected by real-time polymerase chain reaction for quantitative analysis and protein immunoblotting. Results The SA-ALI mouse model was successfully established. Compared with the sham operation group, mice in the CLP group showed disturbed alveolar structure, obvious alveolar and interstitial haemorrhage and inflammatory cell infiltration, elevated serum levels of IL-6, TNF-α and IL-1β (P<0.05), significantly increased mRNA and protein expression of OPG and elevated OPG/RANKL ratio in lung tissue (P<0.05), whereas RANKL mRNA and protein expression was significantly decreased (P<0.05). Compared with the CLP group, the pathological damage of lung tissue in the RANKL group was reduced, the infiltration of alveolar and interstitial inflammatory cells was significantly improved, and the alveolar structure and morphology were more regular, with lower serum levels of IL-6, TNF-α and IL-1β (P<0.05), significantly lower mRNA and protein expression of OPG and OPG/RANKL ratio in lung tissue (P<0.05), and significantly higher mRNA and protein expression of RANKL in lung tissue (P<0.05). Conclusion The alteration of OPG/RANKL ratio may be related to the pathophysiological process of SA-ALI, and the decrease in its level may reflect the attenuation of the inflammatory response in SA-ALI.
Objective To investigate the effect and potential mechanism of bone marrow mesenchymal stem cells (BMSCs) - derived extracellular vesicles (EVs) on lung tissue injury in mice with severe acute pancreatitis (SAP). Methods A total of 24 specific pathogen free grade male C57BL/6 mice and primary mouse lung microvascular endothelial cells (PMVECs) were selected. The mice were divided into sham group, SAP group, and BMSC group, with 8 mice in each group. The mouse primary PMVECs were divided into model group [sodium taurocholate (NaTC) group], BMSC-EV group, and control group. Extraction and characterization of healthy mouse BMSCs and their derived extracellular vesicles (BMSC-EVs) were conducted. A mouse model of SAP was established, and BMSC-EVs were injected into SAP mice by tail vein or intervened in PMVECs in vitro, to observe the pathological damage of pancreatic and lung tissues, the changes of serum amylase, lipase, and inflammatory factors [tumor necrosis factor α (TNF-α), interleukin-6 (IL-6)], the expression of inflammatory factors of lung tissues and PMVECs, and the endothelial cell barrier related proteins [E-cadherin, ZO-1, intercellular cell adhesion molecule-1 (ICAM-1)], and tight junctions between PMVECs to explore the effects of BMSC-EVs on pancreatic and lung tissues in SAP mice and PMVECs in vitro. Results BMSCs had the potential for osteogenic, chondrogenic, and lipogenic differentiation, and the EVs derived from them had a typical cup-shaped structure with a diameter of 60-100 nm. BMSC-EVs expressed the extracellular vesicle-positive proteins TSG101 and CD63 and did not express the negative protein Calnexin. Compared with the mice in the sham group, the SAP mice underwent significant pathological damage to the pancreas (P<0.05), and their serum amylase, lipase, inflammatory factor IL-6, and TNF-α levels were significantly up-regulated (P<0.05); whereas, BMSC-EVs markedly ameliorated the pancreatic tissue damage in the SAP mice (P<0.05), down-regulated the levels of peripheral serum amylase, lipase, IL-6 and TNF-α (P<0.05), and up-regulated the level of anti-inflammatory factor IL-10 (P<0.05). In addition to this, the SAP mice showed significant lung histopathological damage (P<0.05), higher neutrophils and macrophages infiltration (P<0.05), higher levels of the inflammatory factors TGF-β and IL-6 (P<0.05), as well as reduced barrier protein E-cadherin, ZO-1 expression and elevated expression of ICAM-1 (P<0.05). BMSC-EVs significantly ameliorated lung histopathological injury, inflammatory cells infiltration, inflammatory factor levels, and expression of barrier proteins, and suppressed ICAM-1 expression (P<0.05). In the in vitro PMVECs experiments, it was found that intercellular tight junctions were broken in the NaTC group, and the levels of inflammatory factors TNF-α and IL-6 were significantly up-regulated (P<0.05), the protein expression of E-cadherin and ZO-1 was significantly down-regulated (P<0.05), and the expression of ICAM-1 was significantly up-regulated (P<0.05). BMSC-EVs significantly improved intercellular tight junctions in the NaTC group and inhibited the secretion of TNF-α and IL-6 (P<0.05), up-regulated the expression of the barrier proteins E-cadherin and ZO-1, and down-regulated the expression of ICAM-1 (P<0.05). Conclusion BMSC-derived EVs ameliorate lung tissue injury in SAP mice by restoring the lung endothelial cell barrier and inhibiting inflammatory cell infiltration.
Objective To investigate the protective effect of annexin A1 (ANXA1) derived from human umbilical cord mesenchymal stem cells (HucMSCs) on lipopolysaccharide (LPS) -induced acute lung injury (ALI). Methods Six-week-old male C57BL/6 mice were randomly divided into a sham group, a LPS group, a LPS+HucMSC-cm (LPS+cm) group, a LPS+nc-cm group, and a LPS+si-cm group, with 6 mice in each group. LPS (5 mg/kg) was intratracheally injected to induce ALI model. Then, normal saline, HucMSC-cm (HucMSC conditioned medium), HucMSC-nc-cm (normal ANXA1 expression) and HucMSC-si-cm (knockout of ANXA1) were injected intratracheally with 50 μL each after LPS treatment for 4 hours. After 72 hours of LPS administration, the mice were killed, and the blood and lung tissues were retained. After corresponding treatment, the blood and lung tissues were preserved. The expression of IL-6 in peripheral blood of mice was detected by enzyme-linked immunosorbnent assay, the pathological changes of lung tissues were observed by hematoxylin-eosin staining, and the expressions of interleukin-6 (IL-6) and vascular cell adhesion molecule-1 (VCAM-1) in lung tissues of each group were detected by Western blot and immunohistochemistry. Results Compared with the sham group, the lung histopathology of mice in the LPS group showed significantly increased inflammatory factor infiltration, alveolar collapse, and lung tissue structure destruction as well as lung tissue injury score and wet/dry weight ratio (W/D) increased (all P<0.05). Accordingly, IL-6 and VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were increased (all P<0.05). Compared with the LPS group, the pathological injury of lung tissue in the LPS+cm group was improved, the lung tissue injury score and the W/D ratio decreased while IL-6, VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were decreased (all P<0.05). But there were no significant differences between the LPS+cm group and the LPS+ nc-cm group (all P>0.05). Compared with the LPS+nc-cm group, lung tissue pathological injury was aggravated again, lung tissue injury score and W/D were also increased in the LPS+si-cm group (all P<0.05). IL-6 and VCAM-1 protein levels in lung tissue and IL-6 expression in peripheral blood were increased again (all P<0.05). Conclusion ANXA1 derived from HucMSCs has certain protective effect in LPS-induced ALI model.
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.
急性肺损伤（ALI）和急性呼吸窘迫综合征（ARDS）是指由心源性以外的各种肺内外致病因素所导致的急性进行性缺氧性呼吸衰竭，它们具有性质相同的病理生理改变，严重的ALI或ALI的最终严重阶段被定义为ARDS，临床表现以呼吸窘迫、顽固性低氧血症和非心源性肺水肿为特征，采用常规的治疗难以纠正其低氧血症，死亡率高达60%。目前，有关ALI/ARDS的研究取得较多进展，其中，能有效评估ALI病情和预测死亡率的临床参数和生化指标一直是研究热点。
ObjectiveTo study the expression of cytokine-induced neutrophil chemoattractant-1(CINC-1)in rats with transfusion-related acute lung injury(TRALI),explore its possible role in the pathogenesis of TRALI. MethodsSixty Sprague-Dawley rats were randomly divided into a normal control group with sham operation,a positive control group with ALI induced by intravenous infusion of lipopolysaccharide(5 mg/kg),and a TRALI group treated by intraperitoneal injection of LPS 2h before the transfusion of human plasma (1mL),a LPS control group treated by intraperitoneal injection of LPS 2h before the transfusion of normal saline(1mL).The reverse transcription-polymerase chain (RT-PCR)was used to detect CINC-1 mRNA.The level of CINC-1 in lung tissue homogenate was measured by ELISA.Morphological changes of the lung tissue were observed under light microscope.Myeloperoxidase (MPO)in lung homogenate and wet lung weight to dry lung weight ratio (W/D)were observed.The number of cells and the percentage of polymorphonuclear neutrophil (PMN)in Bronchoalveolar lavage fluid (BALF)were also compared. ResultsCompared with the normal control group and the LPS control group,the expression of CINC-1 protein and CINC-1 mRNA were increased significantly in lung of the positive control group and the TRALI group(P<0.05).The number of cells and the percentage of PMN in BALF of the TRALI group [(310.63±76.67)×106/L and (33.57±11.51)%] were significantly higher than those in BALF of the normal control group [(101.36±63.83)×106/L and (9.87±3.56)%](P<0.05).Tissue water content and MPO activity in the TRALI group were significantly higher than those in the normal control group (P<0.05). ConclusionExpression of CINC-1 protein and CINC-1 mRNA are increased in the rat lung with TRALI and PMN infiltration in lung tissue,which suggests CINC-1 participate in the process of the PMN and endothelial cell adhesion and may play an important role in the pathogeneses of TRALI.
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.
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.
ObjectiveTo investigate the effects of human placental mesenchymal stem cells (hPMSCs) transplantation on pulmonary vascular endothelial permeability and lung injury repair in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI).MethodsThe hPMSCs were isolated from the human placental tissue by enzyme digestion and passaged. The cell phenotype of the 3rd generation hPMSCs was detected by flow cytometry. Twenty-four 6-week-old healthy male C57BL/6 mice were randomly divided into 3 groups (n=8). The mice were instilled with LPS in the airway to prepare an ALI model in the ALI model group and the hPMSCs treatment group, and with saline in the control group. At 12 hours after LPS infusion, the mice were injected with 3rd generation hPMSCs via the tail vein in hPMSCs treatment group and with saline in the ALI model group and the control group. At 24 hours after injection, the lung tissues of all mice were taken. The pathological changes were observed by HE staining. The wet/dry mass ratio (W/D) of lung tissue was measured. The Evans blue leak test was used to detect the pulmonary vascular endothelial permea bility in mice. The expression of lung tissue permeability-related protein (VE-cadherin) was detected by Western blot.ResultsFlow cytometry examination showed that the isolated cells had typical MSCs phenotypic characteristics. Mice in each group survived. The alveolar structure of the ALI model group significantly collapsed, a large number of inflammatory cells infiltrated, and local alveolar hemorrhage occurred; while the alveolar structure collapse of the hPMSCs treatment group significantly improved, inflammatory cells infiltration significantly reduced, and a few red blood cells were in the interstitial lung. W/D and exudation volume of Evans blue stain were significantly higher in the ALI model group than in the control group and the hPMSCs treatment group (P<0.05), in the hPMSCs treatment group than in the control group (P<0.05). The relative protein expression of VE-cadherin was significantly lower in the ALI model group than in the control group and the hPMSCs treatment group (P<0.05), and in the hPMSCs treatment group than in the control group (P<0.05).ConclusionIntravenous injection of hPMSCs can effectively reduce the increased pulmonary vascular endothelial permeability mediated by LPS, relieve the degree of lung tissue damage, and play a therapeutic role in ALI mice.