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.
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.
Objective To analyze the role of lienal polypeptide injection in acute lung injury induced by lipopolysaccharide (LPS) in rats. Methods Eighty male SD rats were randomly allocated into 4 groups: a LPS group, a control group, a lienal polypeptide group and a LPS+ lienal polypeptide group (20 rats in each group). Lienal polypeptide or normal saline was given with an intramuscular injection 30 min after an intraperitoneal injection of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 4 h after LPS challenge by enzyme-linked immunosorbent assay (ELISA), wet-to-dry weight ratio, hematoxylin and eosin (HE) staining, TUNEL and Western blotting. Results Lienal polypeptide injection treatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. Moreover lienal polypeptide injection significantly suppressed LPS-induced activation of metastasis-associated protein-1 (MTA1). Conclusion Lienal polypeptide injection is demonstrated to protect rats from LPS-induced acute lung injury by the expression of MTA1.
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.
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.
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 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.
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.
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.