Objective To investigate the mechanismof lung injury caused by paraquat poisoning by observing the changes of fibrogenic cytokines in acute paraquat poisoned rats and the effects of pyrrolidine dithiocarbamate ( PDTC) . Methods Sprague-Dawley rats were randomly divided into three groups, ie. acontrol group ( n =6) , a PDTC group ( n =36) , a paraquat group ( n = 36) , and a paraquat + PDTC group( n =36) . The rats in the PDTC group, the paraquat group, and the paraquat + PDTC group were subdivided into 6 subgroups sacrificed respectively on 1st, 3rd,7th,14th, 28th and 56th day after the treatment. The levels of transforming growth factor-β1( TGF-β1 ) , platelet-derived growth factor ( PDGF) , insulin-like growthfactor-1 ( IGF-1) in serum were measured. Meanwhile the expression of connective tissue growth factor ( CTGF) and hydroxyproline in lung tissues were detected. The relationship of above cytokines with hydroxyproline was analyzed. Results The destructive phase in early ( 1 ～7 d) was characterized by hemorrhage, alveolar edema, and inflammatory cell infiltration. The proliferous phase in later stage ( 14 ～56 d) was characterized by diffused alveolar collapse with fibroblast proliferation and patchy distribution of collagen fibers. Compared with the control group, the level of TGF-β1 on all time points, the level of PDGF from7th to 56th day, the level of IGF-1 from3rd to 56th day in the paraquat group all significantly increased ( P lt;0. 01) . Immunohistochemistry results showed CTGF positive cells mainly located in aleolar epithelialcells, endothelial cells,macrophages in early stage, and fibroblasts were main positive cells on the 28th and the 56th day. The expression of CTGF in the paraquat group increased gradually compared with the control group on different time points ( P lt; 0. 05 or P lt; 0. 01) . Meanwhile, the levels of above cytokines were positively correlated with the level of hydroxyproline. Noteworthy, PDTC treatment led to significant decreases of above cytokines compared with the paraquat group in corresponding time points ( P lt;0. 05 or P lt;0. 01) .Conclusions Over expressions of IGF-1, TGF-β1 , PDGF, IGF-1 and CTGF may play important roles in lung fibrosis of paraquat poisoned rats. PDTC, as a b NF-κB inhibitor, may inhibits NF-κB activity and further significantly decreases expressions of cytokines, leading to significantly attenuated pulmonary inflammation and fibrosis. However, the mechanisms of PDTC intervention still remain to be explored.
With the growth of offshore activities, the incidence rates of seawater drowning (SWD) induced acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) increase significantly higher than before. Pulmonary interstitial edema, alveolar septum fracture, red blood cells, and inflammatory cells infiltration can be seen under light microscope in the pathologic changes of lungs. The major clinical manifestations are continual hyoxemia and acidosis, which lead to a severe condition, a high death rate, and a poor treatment effect. Bone marrow mesenchymal stem cells are capable of self-renewal, multilineage differentiation and injured lung-homing, which are induced to differentiate into alveolar epithelial cells and pulmonary vascular endothelial cells for tissues repairing. This may be a new way to treat SWD-ALI and SW-ARDS.
ObjectiveTo compare two different ways to establish mouse model with acute lung injury (ALI) via intratracheal instillation or intraperitoneal injection of lipopolysaccharide (LPS). MethodsBALB/c mice received intraperitoneal/intratracheal administration of LPS or sham operation. Wet/dry lung weight ratio, protein concentration in bronchoalveolar lavage fluid (BALF), and lung tissue histology were examined at 0, 1, 2, 6, 12, 18, 24, 48 h after LPS administration. Tumor necrosis factor-α (TNF-α) in BALF and serum was assayed with ELISA method. ResultsLPS treatment significantly increased wet/dry lung weight ratio, BALF protein concentration and TNF-α concentration in serum and BALF. Lung tissue was damaged after LPS challenge. The mice received LPS intraperitoneal injection got a more significant lung edema than those received LPS intratracheal instillation. Inversely, LPS intratracheal instillation induced more severed microstructure destruction. ConclusionsALI animal model by LPS intratracheal instillation or intraperitoneal injection induces inflammation and tissue damage in lung. However, the degree of tissue damage or self-healing induced by two methods is different. Therefore the decision of which way to establish ALI model will depend on the study purpose.
Objective To observe the effects of nitric oxide ( NO) inhalation on lung inflammation of acute lung injury ( ALI) in rats. Methods Twenty-four SD rats were randomly divided into four groups, ie. a normal control group, an ALI group, a 20 ppm NO inhalation group, and a 100 ppm NO inhalation group. ALI model was established by LPS instillation intratracheally and the control group was instilled with normal saline. Then they were ventilated with normal air or NO at different levels, and sacrificed 6 hours later. Pathological changes were evaluated by HE staining. The expression of TLR4 in lung tissues was detected by immunohistochemistry. IL-6 level in lung homogenate was measured by ELISA. Results In the ALI group, the inflammation in bronchus and bronchioles was more apparently, and the expressions of TLR4and IL-6 were elevated significantly compared with the control group. 20 ppm NO inhalation significantly decreased the expression of TLR4 and IL-6, and alleviated the inflammation of ALI. However, 100 ppm NO inhalation did not change TLR4 expression and lung inflammation significantly, and increased IL-6 level.Conclusions Inhalation low level of NO( 20 ppm) can alleviate lung inflammation possibly by reducing theexpression of TLR4 and IL-6.
ObjectiveTo explore the value of procalcitonin-to-albumin (PAR) in patients with acute respiratory distress syndrome (ARDS).MethodsA retrospective study was carried on patients diagnosed with ARDS from December 2016 to March 2018. The receiver-operating characteristics (ROC) curve was used to identify the cutoff value of PAR. The association of PAR and 28-day mortality was evaluated using univariate and multivariable Cox regression.ResultsIn the final analysis, there were a total of 255 patients included. Of whom 164 (64.3%) was male, 91 (35.7%) was female and the mean age was 52.1±14.5 years old. The 28-day mortality of all the patients was 32.9% (n=84). ROC curve revealed that the cutoff value of PAR was 0.039 (specificity: 0.714, sensitivity: 0.702) and area under the curve was 0.793 (95%CI: 0.735 - 0.850, P<0.001). The following variables were considered for multivariable adjustment: age, body mass index, pneumonia, aspiration, sepsis, surgery, PaO2/FiO2, red blood cell counts and PAR (P<0.01 in univariate analysis). After multivariable analysis, only age (HR: 1.033, 95%CI: 1.009 - 1.059, P=0.008), PaO2/FiO2 (HR: 0.992, 95%CI: 0.985 - 1.000, P=0.044) and PAR (HR: 4.899, 95%CI: 2.148 - 11.174, P<0.001) remained independently associated with 28-day mortality (P<0.05).ConclusionHigh PAR predicts a poor outcome in ARDS patients, therefore it appears to be a prognostic biomarker of outcomes in patients with ARDS.
Objective To investigate the role of long chain non coding ribonucleic acid (LNcRNA) small nucleolar RNA host gene 14 (SNHG14) in regulating microribonucleic acid 223-3p (miR-223-3p) in alleviating sepsis associated lung injury in rats. Methods Sepsis rat models were established and the rats were randomly divided into SNHG14 upregulation group, SNHG14 upregulated control group, SNHG14 downregulation group, SNHG14 downregulation control group, miR-223-3p upregulation group, miR-223-3p upregulation control group, miR-223-3p downregulation group, miR-223-3p downregulation control group, and model group. Sham operation group was set up simutalously. All of them were administered through the tail vein. After 48 hours, the lung tissues was euthanized to detect the expressions of LncRNA SNHG14 and miR-223-3p. Tumor necrosis factor α (TNF- α), interleukin-1β (IL-1β), interleukin-18 (IL-18), lung wet weight/dry weight ratio (W/D) and the alveolar fluid clearance rate (AFC) were detected. Pathological changes in lung tissues were observed. Human NOD like receptor family protein 3 (NLPR3), cysteine-requiring aspartate protease 1 (caspase-1), and 1-aminocyclopropane-1-carboxylate synthase (ACS) genes and proteins expressions in lung tissues were detected. The dual luciferase reporter gene experiment was used to verify the targeted regulatory effect of LncRNA SNHG14 on miR-223-3p. Results Compared with the sham operation group, the model group showed increase in lung tissue LncRNA SNHG14 expression, serum inflammatory factor levels, W/D, pathological change quantification score, and lung tissue NLPR3, caspase-1 and ACS expressions (P<0.05), decrease in miR-223-3p expression and AFC (P<0.05). Compared with the model group and corresponding control groups, the SNHG14 upregulation group showed increase in LncRNA SNHG14 expression (P<0.05), and the SNHG14 upregulation group and the miR-223-3p downregulation group showed decrease in miR-223-3p expression and AFC (P<0.05), and increase in the levels of serum inflammatory factors, W/D, quantitative scores of pathological changes, and the expressions of NLPR3, caspase-1 and ACS in lung tissues (P<0.05). Compared with the model group and corresponding control groups, the expression of LncRNA SNHG14 in the SNHG14 downregulation group decreased (P<0.05), while the expression of miR-223-3p and AFC in the SNHG14 downregulation group and miR-223-3p upregulation group increased (P<0.05), which showed decrease in the levels of serum inflammatory factors, W/D, quantitative scores of pathological changes, and the expressions of NLPR3, caspase-1 and ACS in lung tissues (P<0.05). There were binding sites between LncRNA SNHG14 and miR-223-3p, and the former could negatively feedback targeted to regulate the latter. Conclusion Downregulation of LncRNA SNHG14 targets an increase in miR-223-3p expression and inhibit the NLRP3 pathway to alleviate sepsis related lung injury, which is related to the inhibition of inflammatory response, while upregulation of LncRNA SNHG14 negatively feedback targeting miR-223-3p and activated the NLRP3 pathway to exacerbate sepsis related lung injury.
ObjectiveTo observe repairing process of trachea epithelium cells in chlorine-induced airway epithelial injury.MethodsTwelve mice were exposed to chlorine gas and prepared the mice model of airway damage. Three mice were executed respectively on 2nd, 4th, 7th, 10th day after exposure to chlorine gas, and tracheal tissues were collected. In addition 3 normal mice served as control. Airway repair and cell proliferation were detected by EdU labeling method. The basal cell markers keratin 5 (K5), keratin 14 (K14) were adopted as the tracheal epithelial markers for locating the position of the proliferation of repairing cells. Morphological analysis was adopted to measure the proliferation rate as well as the recovery of the false stratified epithelium.ResultsIn the control group, cell proliferation rate was very low, all basal cells expressed K5, and most basal cells did not express K14. Most of epithelial cells shed from the trachea epithelium after exposure to chlorine gas. 2-4 days after chlorine exposure, K5 and K14 expression basal cells increased, K14 expression cells increased greatly. In the peak period of cell proliferation, only a small number of ciliated cells appeared in the repairing trachea area. Epithelial cells repaired fast and widely at the bottom of the trachea.ConclusionThe trachea residual basal cells play roles of progenitor cells and repair the airway epithelium after chlorine damage in mice.
Objective To observe whether additional penehycl idine hydrochloride (PHC) in mechanical ventilation produces therapeutic effect on oleic acid (OA) induced acute lung injury (ALI) in canine. Methods Seventeen male canines (weighing 12-17 kg) were divided into control group (n=5), OA group (n=6) and PHC group (n=6). ALI model was developed by central venous injection of OA in canines of OA and PHC groups. ALI model was kept steady in air, all groups received mechanical ventilation 90 minutes later. Three groups received normal sal ine 0.25 mg/kg without injection of OA(control group), normal sal ine 0.25 mg/kg after injection of OA (OA group) and PHC 0.25 mg/kg after injection of OA (PHCgroup) respectively at 0 h (90 minutes after onset time of ALI/ARDS). The heart rate (HR), mean arteial pressure (MAP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), pulmonary artery wedge pressure (PAWP), artery blood gas analysis, cardiac output (CO), extravascular lung water index (EVLWI), FiO2 and VT were observed respectively at basel ine, onset time of ALI/ARDS and 0 h, then again at 1 hour intervals for 6 hours. Besides the above, airway peak pressure (Ppeak), airway plat pressure (Pplat), mean airway pressure (Pmean) and positve end-expriatory pressure (Peep) were also observed each hour during 1-6 hours. Oxygenation index (OI), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), alveolar-arterial differences for O2 (AaDO2) and dynamic lung compl iance (DLC) were calculated and pulmonary tissue was collected for histopathologic investigation and dry wet weight ratio (WDR) test. Results The functional parameters of PHC group were improved when compared those of OA group, but there was no siginficant difference; WDR of independent region of three groups were 80.42% ± 3.48%, 82.67% ± 4.01% and 82.26% ± 1.43% respectively; WDR of dependent region of three groups were 80.51% ± 3.60%, 83.71% ± 1.98% and 82.57% ± 1.08% respectively. WDR of PHC group were obviously improved when compared with those of OA group, but there was no significant difference. Independent and dependent regions of PHC group were significantly improved when compared those of OA group in histopathologic scores, alveolar edema, inflammatory infiltration and over-distension (P lt; 0.01). Conclusion Additional PHC in mechanical ventilation produces obvious therapeutic effect on OA induced acute lung injury in canine.
ObjectiveTo study the effects of hydroxysafflow yellow A (HSYA) in inhibiting inflammatory signal transduction in lungs of acute lung injury mice induced by lipopolysaccharide (LPS). MethodsEighty-four male Kunming mice were randomly divided into 7 groups, ie. a sham group, a LPS group, a LPS+3 mg/kg dexamethason (DXM) group, a LPS+6 mg/kg HSYA group, a LPS+15 mg/kg HSYA group, a LPS+37.5 mg/kg HSYA group, and a saline+37.5 mg/kg HSYA group (n=12 in each group). The mice were intraperitoneally pretreated with normal saline or DXM or HSYA 0.5 hour prior to intravenous adminstration of LPS. TNF-α, IL-1β and IL-6 levels in mice serum were measured by ELISA and the mRNA and protein levels of TLR4 in mice lungs were assessed by RT-qPCR and Western blot, respectively. ResultsAfter being treated with HSYA in doses of 6 mg/kg, 15 mg/kg, and 37.5 mg/kg, the increased expression levels of TLR4 mRNA and protein induced by LPS were significantly inhibited, as well as the increased expression levels of TNF-α, IL-1β and IL-6. The inhibitoty effect enhanced with the doses of HSYA. DXM could inhibit more significantly the increased expression levels of all the indexes. ConclusionHSYA can inhibit inflammatory signal transduction in acute lung injury mice induced by LPS in a dose-dependent manner, but is less effective than DXM.
Objective To evaluate the efficiency and associated factors of noninvasive positive pressure ventilation( NPPV) in the treatment of acute lung injury( ALI) and acute respiratory distress syndrome( ARDS) .Methods Twenty-eight patients who fulfilled the criteria for ALI/ARDS were enrolled in the study. The patients were randomized to receive either noninvasive positive pressure ventilation( NPPV group) or oxygen therapy through a Venturi mask( control group) . All patients were closely observed and evaluated during observation period in order to determine if the patients meet the preset intubation criteria and the associated risk factors. Results The success rate in avoiding intubation in the NPPV group was 66. 7%( 10/15) , which was significantly lower than that in the control group ( 33. 3% vs. 86. 4% , P = 0. 009) . However, there was no significant difference in the mortality between two groups( 7. 7% vs.27. 3% , P =0. 300) . The incidence rates of pulmonary bacteria infection and multiple organ damage were significantly lower in the NPPV success subgroup as compared with the NPPV failure group( 2 /10 vs. 4/5, P =0. 01;1 /10 vs. 3/5, P = 0. 03) . Correlation analysis showed that failure of NPPV was significantly associated with pulmonary bacterial infection and multiple organ damage( r=0. 58, P lt;0. 05; r =0. 53, P lt;0. 05) . Logistic stepwise regression analysis showed that pulmonary bacterial infection was an independent risk factor associated with failure of NPPV( r2 =0. 33, P =0. 024) . In the success subgroup, respiratory rate significantly decreased( 29 ±4 breaths /min vs. 33 ±5 breaths /min, P lt; 0. 05) and PaO2 /FiO2 significantly increased ( 191 ±63 mmHg vs. 147 ±55 mmHg, P lt;0. 05) at the time of 24 hours after NPPV treatment as compared with baseline. There were no significant change after NPPV treatment in heart rate, APACHEⅡ score, pH and PaCO2 ( all P gt;0. 05) . On the other hand in the failure subgroup, after 24 hours NPPV treatment, respiratory rate significantly increased( 40 ±3 breaths /min vs. 33 ±3 breaths /min, P lt;0. 05) and PaO2 /FiO2 showed a tendency to decline( 98 ±16 mmHg vs. 123 ±34 mmHg, P gt; 0. 05) . Conclusions In selected patients, NPPV is an effective and safe intervention for ALI/ARDS with improvement of pulmonary oxygenation and decrease of intubation rate. The results of current study support the use of NPPV in ALI/ARDS as the firstline choice of early intervention with mechanical ventilation.