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Objective? ? To? evaluate? the? protective? effect? and? curative? effect? of? early? treatment? with?extracorporeal?membrane?oxygenation?(ECMO)?in?severe?patients?with?acute?respiratory?distress?syndrome?(ARDS)?caused?by?acute?phosgene?poisoning.? Methods? The?course?of?treatment?of?4?cases?of?ARDS?caused?by?acute?phosgene?poisoning?admitted?to?intensive?care?unit?(ICU)?of?Jiangxi?Provincial?People's?Hospital?in?April?2018?was?retrospectively?analyzed.?The?treatment?parameters?in?patients?before?and?after?the?ECMO?treatment?at?1,?3,?7?days?were?collected,?including?pH?of?the?arterial?blood,?arterial?partial?pressure?of?carbon?dioxide?(PaCO2),?arterial?partial?pressure?of?oxygen?(PaO2),?blood?lactic?acid?(Lac)?and?systemic?vascular?resistance?index?(SVRI),?cardiac?index?(CI),?extravascular?lung?water?index?(ELWI),?plateau?pressure?(Pplat),?positive?end-expiratory?pressure?(PEEP),?driving?pressure?(ΔP),?and?acute?physiology?and?chronic?health?evaluation?Ⅱ?(APACHE?Ⅱ),?the?length?of?ICU?stay,?the?treatment?duration?of?ECMO?and?the?duration?of?mechanical?ventilation.? Results? After?admitted?in?hospital,?the?4?patients?were?all?put?on?tracheal?intubation?and?ventilator,?but?the?ventilator?support?conditions?were?high,?the?oxygenation?and?internal?environment?were?unstable.?Therefore,?ECMO?therapy?was?performed?on?the?next?day?after?admission.?Oxygenation?was?improved?obviously?after?treatment,?ventilator?support?conditions?could?be?obviously?reduced,?including?3-6?mL/kg?of?the?small?tidal?volume,?8-10?cmH2O?(1?cmH2O?=?0.098?kPa)?of?the?PEEP,?0.30?of?the?inhaled?oxygen?concentration?(FiO2),?and?other?lung?protection?rest?strategies.?The?parameters?were?improved?obviously?after?the?ECMO?treatment?compared?with?before,?from?the?1st?day?after?the?ECMO?treatment,?PaO2,?SVRI?rose?obviously,?Lac,?ELWI,?Pplat,?PEEP,?ΔP,?APACHEⅡ?were?significantly?decreased?[PaO2??(mmHg,?1?mmHg?=?0.133?kPa):?85.5±10.7?vs.?54.2±4.5,?SVRI?(kPa·s·L-1·m-2):?153.6±9.4?vs.?118.0±12.6,?Lac?(mmol/L):?2.15±0.19?vs.?4.93±0.96,?ELWI?(mL/kg):?17.73±2.99?vs.?20.45±4.13,?Pplat?(cmH2O):?19.25±2.21?vs.?35.75±2.22,?PEEP?(cmH2O):?9.0±1.2?vs.?13.5±1.7,?ΔP?(cmH2O):?10.25±1.26?vs.?22.25±3.86,?APACHEⅡ:?17.25±2.22?vs.?26.50±2.08,?all?P?﹤0.05];?pH?and?CI?were?significantly?increased?after?3?days?treatment,?and?PaCO2?was?significantly?decreased?[pH:?7.43±0.05?vs.?7.21±0.13,?CI?(mL·s-1·m-2):?? 64.35±3.17?vs.?59.51±3.17,?PaCO2?(mmHg):?42.0±2.2?vs.?55.0±8.5,?all?P?<?0.05].?All?the?4?patients?were?treated?successfully?and?discharged?after?improvement.?The?length?of?ICU?stay?was?8-27?days,?with?an?average?(13.5±9.0)?days;?the?treatment?duration?of?ECMO?was?6-12?days,?with?an?average?(8.0±2.7)?days;?the?duration?of?mechanical?ventilation?was?6-20?days,?with?an?average?(10.75±6.19)?days.? Conclusion? Early?treatment?with?ECMO?can?significantly?improve?the?oxygenation?of?severe?ARDS?caused?by?acute?phosgene?poisoning,?eliminate?excessive?CO2?in?the?body,?reduce?ventilator-associated?lung?injury,?and?improve?the?prognosis.
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Objective@#To investigate the effects of methylprednisolone on NOD-like receptor hot protein domain-associated protein 3 (NLRP3) inflammasome in phosgene-induced acute lung injury.@*Methods@#Rats were randomly divided into four groups, 10 rats in Air group (inhalation of air of the same volume as the phosgene group) , 10 rats in Phosgene group (inhalation of 8.33 mg/L with 100% purity phosgene for 5 min) , 10 rats in Saline control group (inhalation of the same dose of phosgene and 2 mg/kg saline via tail vein injection one hour later) , 10 rats in MP group (inhalation of the same dose of phosgene and 2 mg/kg MP via tail vein injection one hour later) . The specimens of serum, bronchoalveolar lavage fluid (BALF) and lung tissue were collected after 6h. Morphological changes were observed by HE staining. The expression of NLRP3 in the lung of four groups was detected by immunohistochemistry. NLRP3、ASC and caspase-1 expression in the lung tissue was quantified by Western blot. Reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the expression of NLRP3、ASC and caspase-1 mRNA in the lung tissue. The concentrations of IL-1β、IL-18 and IL-33 in the serum and BALF were measured by enzyme-linked immunosorbent assay.@*Results@#We successfully replicated the model of phosgene-induced ALI in rats. Morphological of HE staining after phosgene exposure to 6 h observed inflammatory cell infiltration in lung tissue in Phosgene group. Immunohistochemical staining results showed that there were many NLRP3 positive cells in lung tissue in Phosgene group. The levels of NLRP3, caspase-1 mRNA and protein expression in lung were significantly increased (P<0.05) in Phosgene group compared with Air group; compared with Phosgene group, The levels of NLRP3 and caspase-1 mRNA and protein expression in MP group were significantly decreased (P<0.05) . Compared with Air group, The levels IL-1β、IL-18 and IL-33 mRNA protein expression in the serum and BALF were significantly increased (P<0.05) in Phosgene group. Compared with Phosgene group, The levels IL-1β、IL-18 and IL-33 mRNA protein expression in the serum and BALF were significantly decreased (P<0.05) in MP group.@*Conclusion@#Methylprednisolone can effectively protect the rats from phosgene-induced acute lung injury by inhibiting the expression of the NLRP3 inflammasome and reducing the release of inflammatory factors such as interleukin-1β (IL-1β) mediated by it.
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Objective To observe the effect of signal transduction pathway of nuclear factor-kappa B (NF-κB) on Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome and pyroptosis in rats with acute lung injury induced (ALI) by phosgene. Methods The rats were randomly(random number) divided into 3 groups: air exposure control group, phosgene exposure group and PDTC group with phosgene exposure after 100 mg/kg pyrrolidine dithiocarbamate (PDTC) administration. The specimens of serum, bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h after exposure. Morphological changes were observed by HE staining. The expression of NLRP3 in the lung of three groups was detected by immunohistochemistry. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expressions of NF-κB p65, NLRP3, ASC and caspase-1 mRNA in the lung tissue. NF-κB p65,NLRP3, ASC and caspase-1 protein levels in the lung tissue were quantified by Western blot. The concentrations of IL-1β, IL-18 and IL-33 in the serum and BALF were measured by enzyme-linked immunosorbent assay (ELISA). Pyroptosis was observed by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL). Results The model of phosgene-induced ALI was successfully established in rats. Morphological changes with inflammatory cell infiltration were observed in the lung tissues of phosgene group, in which NLRP3 positive cells also could be observed by immunohistochemical staining. The mRNA expressions and protein levels of NF-κB p65, NLRP3 and caspase-1 in lung tissues were significantly increased (P＜0.05) in phosgene group, compared with air control group. The mRNA expressions and protein levels of NF-κB p65,NLRP3 and caspase-1 in lung tissues were significantly decreased (P＜0.05) in PDTC group, compared with phosgene group. The IL-1β,IL-18 and IL-33 protein levels in serum and BALF were significantly increased (P＜0.05) in phosgene group, compared with air control group. The IL-1β,IL-18 and IL-33 protein levels in serum and BALF were significantly decreased (P＜0.05) in PDTC group, compared with phosgene group. TUNEL results showed that pyroptosis in the lung tissue obviously increased in phosgene group, while decreased in PDTC group. Conclusions NLRP3 inflammasome and lung cell pyroptosis were induced through NF-kB signal transduction pathway in rats with acute lung injury caused by phosgene inhalation. Blockade of NF-κB can alleviate acute lung injury by down-regulating the expression of NLRP3 inflammasome to inhibit pyroptosis.
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Objective@#To investigate changes of NLRP3 signal transduction pathway of acute lung injury induced by phosgene to analyze NLRP3-mediated IL-1β release inflammatory process in rats.@*Methods@#Rats were randomly divided into two groups, 10 rats in the Air group that consists of the rats with air exposure, 10 rats in the Psg group that consists of the rats with phosgene exposure at 8.33 g/m3 for 5 min. The specimens of serum, bronchoalveolar lavage fluid (BALF) and lung were collected after 6h. Morphological changes were observed by HE staining. The expression of NLRP3 in the lung of two groups was detected by immunohistochemistry. NLRP3、ASC and caspase-1 expression in the lung tissue was quantified by Western blot. Reverse transcription-polymerase chain reaction (RT-PCR) were used to detect the expression of NLRP3、ASC and caspase-1 mRNA in the lung tissue. The concentrations of IL-1β、IL-18 and IL-33 in the serum and BALF were measured by enzyme-linked immunosorbent assay. RT-PCR were used to detect the expression of IL-1β、IL-18 and IL-33 mRNA in the lung tissue.@*Results@#We successfully replicated the model of phosgene-induced ALI in rats. Morphological of HE staining after phosgene exposure to 6 h observed inflammatory cell infiltration in lung tissue in Phosgene group. Immunohistochemical staining results showed that there were many NLRP3 positive cells in lung tissue in Phosgene group. The levels of NLRP3 and caspase-1 mRNA and protein expression in lung were significantly increased (P<0.05) in Phosgene group, but no significant change was observed in lung ASC mRNA and protein expression (P>0.05) . Compared with Air group, the serum, BALF and lung tissue of IL-1β、IL-18 and IL-33 mRNA and protein expression were significantly increased (P<0.01) in Phosgene group.@*Conclusion@#NLRP3-mediated inflammatory response probably involved in the process of the phosgene, so it maybe one of the pathogenesis of acute lung injury.
ABSTRACT
Lung is the main target of lung-damaging agents(or choking agents,lung irritants)which can result in potential permanent respiratory depression,the rapid development of acute lung injury(ALI)and pulmonary edema,even death in severe cas-es. Recently,with the research progress in the pathogenesis of lung-damaging agents,numerous corresponding experimental studies were carried out and some progress were made. This paper summarizes the progress in the study of lung-damaging agents on the re-search situation,pathogenic mechanism and biomarker,to provide reference for the promotion of ALI prevention,medical antagonis-tic measures and clinical treatment.
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Objective To investigate the effect of dexamethasone on expressions of angiopoietin-1,2 (Ang-1,2) in rats with acute lung injury induced by phosgene.Methods A total of 36 SD rats were randomly (random number) divided into 3 groups:normal control group that consisted of the rats with air exposure,phosgene group that consisted of the rats with exposure to 8.33 mg/L phosgene (purity 100％,of the same volume as the inhaled air in the normal control group) for 5 minutes and dexamethasone group that consisted of the rats with caudal vein injection of 2.5 mg/kg dexamethasone an hour before exposure to the same dose of phosgene.Wet and dry ratio of the lung (W/D) was calculated,and leukocyte count and total protein content of bronchoalveolar lavage fluid (BALF) were recorded 2 hours later.The concentrations of Ang-1,2 in the serum and BALF were measured by enzyme-linked immunosorbent assay (ELISA).Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the mRNA levels of Ang-1,2 and Tie-2 in the lung tissue.The protein expression of Ang-1,2 and Tie-2 in the lung tissue were quantified by Western blot.Results Compared with phosgene group,the lung W/D,protein content of BALF and WBC count in dexamethasone group were significantly decreased (P ＜ 0.01).Compared with normal control group,Ang-1 and Tie-2 expressions in phosgene group were significantly decreased (P ＜ 0.01).Compared with phosgene group,the serum,BALF and lung tissue of Ang-1 and Tie-2 expressions in dexamethasone group was significantly increased (P ＜0.01).Compared with normal control group,the serum,BALF and lung tissue of Ang-2 expressions in phosgene group were significantly increased (P ＜ 0.01).Compared with phosgene group,the serum,BALF and lung tissue of Ang-2 expressions in dexamethasone group were significantly decreased (P ＜ 0.05,P ＜ 0.01).Conclusion Dexamethasone has a beneficial effect on acute lung injury induced by phosgene in rats by inhibition of Ang-2 and increase in Ang-1 and Tie-2 expressions.
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Objective To investigate the effects of transient plateau factor on acute lung injury induced by phosgene poisoning in rabbits.Methods Forty New Zealand white rabbits of both sexes,aged 2.0-2.5 kg,were randomly divided into 4 groups (n =10 each) using a random number table:control group (group C),plateau factor group (group H),phosgene poisoning group (group P),and phosgene poisoning and plateau factor group (group HP).In group H,the rabbits were exposed to a simulated altitude of 33000 m for 2 h.In group P,the rabbits were exposed to phosgene for 3 min only.In group HP,the rabbits were exposed to phosgene for 33 min and then to a simulated altitude of 3000 m for 2 h.Respiratory rate (RR) was recorded and blood samples were taken before exposure to phosgene (T1),after exposure to phosgene (T2),and at 0,1 and 6 h after onset of exposure to a simulated altitude of 33000 m (T3-5) for determination of PaO2 and oxygenation index (OI) was calculated.The chests were opened at T5 and lungs removed for determination of lung water content (LC) and for microscopic examination.Lung coefficient (LC) was calculated.Results Compared with C group,RR was significantly increased at T3 in group H (P ＜ 0.05),and RR was increased and OI was decreased at T2-5 in P and HP groups (P ＜ 0.05 or 0.01).Compared with P group,RR was increased and OI was decreased at T3-5 in HP group (P ＜ 0.05 or 0.01).LW and LC were significantly higher in P and HP groups than in group C,and in HP group than in group P (P ＜ 0.05 or 0.01).The microscopic examination showed that pathological changes were observed in P and HP groups,however,the changes were severer in HP group.Conclusion Transient plateau factor can obviously aggravate the degree of acute lung injury induced by phosgene poisoning in rabbits.
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Objective To observe the levels of Ang - 1 and NF-κB in lung tissue and to aseess the severity of ALI induced by phosgene in order to clarify the mechanism of the protective effect of Ang - 1 on phosgene induced ALI.Method Rats were randomly divided into phosgene group and air group.Another rats were randomly (random number) divided into phosgene group,phosgene + PDTC group and air group.Lung tissue was collected to weigh and calculate the wet / dry weight ratio,measure BALF,white blood cell count,total protein and Ang-1 at given time after exposure to phosgene/air and PDTC.The Ang - 1 and NF-κB levels in lung tissue were measured with Western blot and immunohistochemistry.Data were analyzed by using SPSS 16.0 statistical package and comparisons between groups were carried out byusing One-Way ANOVA analysis and LSD -t test,α ＜ 0.05.Results Serum angiopoietin -1 level became lesser within 48 hours after exposure to Phosgene.The severity of ALI became worser with time elapsing.Ccompare with air group,the severity of ALI in phosgene group was worser with time elapsing ( P ＜ 0.05).Compared with phosgene + PDTC group,the serum angiopoietin -1 and arterial oxygen partial pressure in phosgene group were lower ( P ＜ 0.05).The severity of ALI of rats in phosgene group were worser than that in phosgene + PDTC group ( P ＜ 0.05).Serum angiopoietin -1 and partial pressure of oxygen of rats in phosgene group were higher than those in phosgene + PDTC group ( P ＜ 0.05).Immunohistochemistry test showed that the expression of Ang-1 in lung tissue in air group were normal,and Ang-1 in phosgene group were significantly reduced,and Ang-1 in PDTC intervention group was higher than that in phosgene group and lower than that in air group.The above results were confirmed by Western blot test which was consistent with the results of immunohistochemistry test.Similarly,the levels of NF-κB in lung tissue determined by using both Western - blot and immunohistochemistry were consistant,and results of both methods showed that the expression of NF - κB in air group was normal,and it increased in phosgene group,and the expression of NF-κB in phosgene + PDTC group was lower than that in phosgene group.Conclusions The serum level of Ang-1 was decreasing within 48 hours after ALI.Ang-1 was negatively correlated with the sevfity of phosgene induced ALI.Ang-1 likely had an effect on NF-κB signaling pathway,ameliorating the inflammation mediated by cytokines,reducing lung endothelial permeability and in turn lessening the severity of ALI.
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Objective To observe the effects of ulinastatin on the expressions of tumor necrosis factor-α (TNF-α) in the lung tissues of rats with acute lung injmy induced by phosgene, and to explore the mechanism of ulinastafin in treating acute lung injury. Method Sixty-four clean grade healthy male SD rots were randomly divided(random number) into eight groups with eight in each group. Group A1 in which rats were exposed to air. Group A2 in which rots wereexposed to air and treated with saline. Group A3 in which rats were exposed to air and treated with dexamethasone. Group A4 in which mrs were exposed to air and treated with ulinastatin. Group B1 in which rots were exposed to phosgene without treatment. Group B2 in which rats were exposed to phosgene and treated with saline. Group B3 in which rats were exposed to phosgene and treated with dexamethasone. Group B4 in which rats were exposed to phosgene and treated with ulinastatin. The expressions of TNF-α in the lung tissues were measured by using immunohistocheistry. Lung tissues were observed grossly and under 200-fold light microscope to identify the positive expressions in kytoplasm. Results In group B1 and group B2, the wet weight, dry weight and wet/dry weight ratio og right lower lobe of lung were higher thai those in group A1 and group A4( P <0.01 ), and those in group B4 and group B3 were significantly lower than those in group B1(P<0.01 ), but still higher than those in group A1 and A4(P<0.01). The gross observation suggested that the surfaces of lung tissues in group A1and group A2 were slick and rose pink without congestion, dropsy or infarction; the surfaces of lung tissue in groups B1 and B2 appeared with congestion, dropsy and many petechia. The surfaces of lung tissue in groups B3 and B4 were similar to those in groups B1 and B2. Under the light microscope, the structure, of lungs in groups A1 and A2 were clear without congestion, effusion or inflammatory cell infiltration. In groups B1 and B2, the engorgement of lung capillary vessels, congestion and tiny thrombosis were found and there abundant edematous fluid and inflammatory cell infiltration in lung stroma and alveolus with focal pulmonary atelectasis in some lung tissue section. The tissues in groups B3 and B4 showed congestion, dropsy, tiny thrombosis and inflammatory cell infiltration, but these changes were slighter than those in groups B1 and B2. The expressions of TNF-α in groups B1, B2, B3, and B4 were significantly higher thanthose in groups A1 and A2( P < 0.01 ), but the expressions of TNF-α IN group B4 was lower than that in groups B1 and B2(P<0.01). Conclusions Ulinastatin could lessen the lung injury by reducing the expressions of pro-inflammatory cytokines such as TNF-α.
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Objective To explore the clinical features and the cause of secondary phosgene poisoning after rescuing the patients with acute phosgene poisoning.Methods According to the diagnostic criteria of occupational acute phosgene poisoning,the differences of clinical manifestation,laboratory results and chest X-ray between secondary poisoning patients and primary patients were compared.Results Among the 25 patients with secondary phosgene poisoning,14(56.0%) had cough,13(52.0%)had throat stimulus,10(40.0%)had chest stuffiness,2(8.0%)had polypnea,1(4.0%) had pain in the eye.There was no significant difference in clinical manifestation between the secondary and primary patients. No positive sign was found after the examination of pulmonary function in the 25 patients,but all of them had abnormal chest X-ray,and typical bronchitis could be found.According to the diagnostic criteria,the 25 patients had slight acute phosgene poisoning,and recovered after treatment for 7 to 10 days.Conclusion To prevent the secondary phosgene poisoning after treating the patients with acute phosgene intoxication,medical workers should enhance protection awareness and take some necessary measures.
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Objective To study the protective effect of a hyperoxic solution on phosgene-induced lung injury by observing the changes in W/D ratio, lung water (LW), and L/B, and MDA contents, GSH-PX activity, and protein contents in broncho-alveolar lavage fluid (BALF). Methods The rabbits were divided into normal control group, hyperoxic solution (HO) and balance salt(BS) groups.Group HO and Group BS inhaled phosgene, and hyperoxic solution was given intravenously in group HO, but BS was given in group BS. W/D, LW, L/B, and MDA contents,GSH-PX activity,protein contents in broncho-alveolar lavage fluid (BALF) were determined. Results The MDA contents, W/D, LW and L/B were increased, and GSH-PX activity was decreased significantly in Group HO and Group BS compared with control group (P