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 flow 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 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.
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.
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.
Sepsis-associated organ dysfunction arises from uncontrolled inflammation and immune dysregulation, causing microcirculatory impairment and multi-organ failure. Stellate ganglion block (SGB) may confer organ protection by regulating the sympathetic nervous system and hypothalamic-pituitary-adrenal axis to suppress excessive inflammation and oxidative stress. Available evidence, mainly from experimental and small clinical studies, suggests potential benefits of SGB in sepsis-induced acute lung injury, ventricular arrhythmias, and limb ischemia, which require confirmation in multicenter randomized controlled trials. This review outlines the mechanisms and clinical advances of SGB in sepsis-related organ dysfunction, providing a theoretical basis for its application in critical care.
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。
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 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.
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.
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.