| Part Ⅰ Retrospective analysis of clinical features of acute exogenous liposome pneumonia in childrenObjective:Acute exogenous lipoid pneumonia(AELP)is an uncommon condition resulting from aspiration or inhalation of fatty substances like mineral oils and petroleum jelly.However,it is still lack of standards for diagnosis and treatment.Here,the first part of our study was to investigate clinical characteristics,radiological findings and therapies of ELP in healthy children.Methods:21 children with AELP and 25 cases of Community-acquired pneumonia(CAP)hospitalized in our hospital were retrospectively reviewed.The medical records including clinic manifestations,radiologic findings and treatments were analyzed.Results:1.The average age of AELP group was 30.19±14.176 m;The average age of CAP group was 25.24±25.325 m,and there was no statistical difference between the two groups(P>0.05).The duration of the patients from illness to hospitalization were 40.762±54.361 h in AELP group and 150.72±88.323 h in CAP group,and there was a statistical difference between the two groups(P<0.05).The average hospital stay of AELP group was 11.47±10.033 d and 5.04±1.881 d of CAP group.There was statistical difference between the two groups((P<0.01).2.The white blood cell count at admission was 16.016±3.632×19/L in AELP and was 10.078±4.015×109/L in CAP group.There was a statistical difference between the two groups(P<0.01).The CRP were 35.624±39.626 mg/L and 19.197±24.218 mg/L.There was no statistical difference between the two groups(P>0.05).Blood gas analysis of P02 was 83.905±13.172 mmHg at admission of AELP group and P02 95.28±22.731 mmHg of CAP group.lt showed statistically significant differences between the two groups(P<0.05)The average time of the first imaging examination was 40.90±53.35h after aspirating mineral oil.3.The earliest X-ray was done in 3 hours after an accident.Imaging examination findings were abnormal in one side of the lung in four cases;both lungs in 17 cases,mainly located in middle and lower lobes.Chest CT scans showed lobar or segmentalconsolidation(15/21),a geographic lobular distribution of ground-glass opacities at both lungs(3/21),miliary change(2/21),thickening of interstitium and parenchymal distortion(2/21)and cavity(1/21),mediastinal pneumatosis(1/21).All cases were reviewed with imaging,including 16 chest reexamination,5 chest CT reexamination.The duration time of lung exudation is from 8d to 5.5m.The first time of lung imaging in the CAP group was from 3rd to 20d,with an average of 6.92 ± 3.96 d.In 25 cases,chest CT examination was performed in 4 and 21 cases were performed by X-ray.Lung lesions on one side in 12 cases and 13 cases of bilateral lung changes,mainly in the middle and lower leaves.16 cases including 15 cases of chest reexamination and 1 case of chest CT were reviewed with imaging after admission to hospital from 5 to 10 days.4.All patients with AELP received corticosteroid and antibiotic treatments.Four cases accepted treatment by intravenous methylprednisolone with 10mg/kg/day for 3 days followed by 1-2mg/kg/day intravenous methylprednisolone.3 cases were treated with intravenous methylprednisolone 1-2 mg/kg/q8h for 3 days followed by prednisolone.Intravenous methylprednisolone 1-2 mg/kg/q12h for 3 days were followed by 14 cases treatment.11 patients with CAP received antibiotic treatments and 6 ones treated with intravenous methylprednisolone 1-2 mg/kg/q12 h for 3-5 days.Conclusions:AELP in children occurs in almost all cases after mistaking mineral oil.Pulmonary opacities can be found by chest CT in most patients within 6 hours after aspirating mineral oil.Clinical history and CT examination are very helpful for making a diagnosis of lipid pneumonia.The use of glucocorticoids and antibiotics was more common in AELP than CAP.Corticosteroids therapy was effective for patients with AELP which limited inflammatory responses and ongoing pulmonary fibrosis.Depending on presentations of this disease,these lesions should be differentiated from CAP.Part Ⅱ Establishment of rat model of acute exogenous lipid pneumonia and assentment of lung injuryObjective:To explore the establishment of AELP model and the damage lung tissue in rats after oil inhalation.Methods:To design a mineral oil inhalation-induced lung injury model of rat by non-invasive tracheal intubation.The rat model of mineral oil inhalation injury was copied.Twenty-four male SD rats were randomized into 2 group using random number table:NS group(inhaled NS 0.5ml/kg)and AELP group(inhaled mineral oil 0.5ml/kg).Results:Through the method of tracheal intubation through the mouth under non-invasive direct view,the exudation of the lungs in the AELP group was significantly higher than that in the NS group.After 72 hours of modeling,the chest was reviewed,the NS was basically absorbed,and the AELP group was still exudated.No obvious abnormalities in microstructure and ultrastructur were found in NS group.Compared with the control group,after mineral oil inhalation a typical performance of lung injury occurred by gross observation as severe edema,histopathogical observation as the damage of alveolar structure,hualine membrane,alveolar septal thichening,neutrophil and erythrocyte infiltration.By the Sudan Ⅲ staining,macrophages stained with orange-red particles were found.Conclusions:The machine oil can be used for experimental operations and non-invasive tracheal intubation method is suitable for the AELP.The appropriate oil inhaled quantity is 0.5 ml/kg.The pathological changes of lung tissue in the two groups showed that oil inhalation caused lung tissue damage and obvious damage occurred after inhalation for 3-5d.PartⅢ The protective effect and mechanisms of dexamethasone onexogenous lipoid pneumonia in ratsObjective:To explore the protective effect of glucocorticoids on the lung tissue of AELP in rats with the intervention of DXM and Pyrrolidine dithiocarbarate(PDTC),to provide theoretical basis for AELP animal experimental research and to improve clinical diagnosis and treatment.Methods:One hundred healthy male SD rats were randomized into 5 groups using random number table:A group(NS group),B group(AELP group),C group(PDTC group),Dgroup(DXM group)and E group(PDTC+DXM group).Gross observation in lung and lung histopathology,ELISA assay of level of IL-6,TNF-α,MIF,KL-6 in rat bronchoalveolar lavage fluid(BALF)and serum and the expression of NF-κB p65、IKKα、Bcl-2 detected by Western blot and immunohistochemistry.Results:1.Compared with the control group,after machine oil inhalation a typical performance of lung injury occurred.Compared with the group A,the lung injury scores of group B increased significantly at different time(P<0.05).There was statistical difference between group C,E and group B at the four times.(P<0.05);Compared with and group B,the lung injury scores in group D was reduced significantly at the third,fifth and seventh day(P<0.05).2.Compared with group A,the expression of TNF-a in group B increased at four time points in BALF and serum(P<0.05).The expression of TNF-a in group D、E decreased at four time points in BALF and serum compared with group B.There was a statistical difference between group B and group C on 1 st,3rd,5thday in BALF and on 3rd,5th,7th day in serum(P<0.05).The expression of IL-6 in group B increased and there were statistical differences at 4 time points compared with group A in BALF and serum(P<0.05).In BALF,there were statistical difference between group C and group B on 1st and 3rd day(P<0.05),group D and group B on 3rd day(P<0.05).Compared with group B,the expression of IL-6 in group D decreased at four time points in BALF(P<0.05).The expression of IL-6 in group C、D、E decreased at four time points in serum compared with B(P<0.05).Compared with group A,the MIF of group B in BALF increased at 4 time points,and the difference was statistically significant((P<0.05).The difference between group B and group A(in serum)on 3rd and 5th was significantly increased(P<0.05);The treatment group D,E and B group(BALF,serum)decreased at 4 time points,the difference was statistically significant(P<0.05);There were statistically significant differences between the D,E group and group B at all four time points in BALFand serum(P<0.05);C group(BALF)and B group decreased at Id,3d The difference was statistically significant(P<0.05);Compared with group B,the expression in group C decreased on 1st,3rd day inBALF and on 3rd,5th,7th day in serum(P<0.05).3.Changes of KL-6 in each group:the expression was highest in group B,in which the expression was highest on 3rd day.IN group A,KL-6 was the highest on 1st day in BALF and the highest on 3rd day in serum.The expression of group C was lower than group D duringl st to 5th day,while the expression was slightly higher on the 7th day.Expression in group E remained at low level.There were statistically significant differences at 4 time points between group B and group A(P<0.05).There were statistically significant differences between group C,D,E and group B at 4 time points(P<0.05).4.There was a highly positive correlation between TNF-αlevel and IL-6 in serum(r=0.901,P<0.05)and BALF(r=0.849,P<0.05).TNF-αlevel presented a linear correlation trend with MIF level in serum(r=0.778,P<0.05)and BALF(r=0.782,P<0.05).There were a highly positive correlation between KL-6 level and TNF-a(r=0.849,P<0.05),KL-6 level and IL-6(r=0.790,P<0.05)KL-6 level and MIF(r=0.778,P<0.05)in serum.KL-6 presented a linear correlation with TNF-α(r=0.776,P<0.05),IL-6 level(r=0.790,P<0.05),MIF level(r=0.754,P<0.05)in serum MIF level and a highly positive correlation(r=0.806,P<0.05).5.The expression of NF-κB P65 in group B was significantly increased at 4 time points compared with group A(P<0.01).After the drug intervention,the expression of NF-rcB P65 in the lung tissue of rats was inhibited with the lowest level on the 7th day in group C,D and E.There were statistically significantof NF-κB P65 protein expression in group C,D,E and group B at 4 time points(P<0.05),and NF-κB P65 protein expression in group D and E decreased compared with that in group C on 5th and 7th day(P<0.05).6.The expression of IKKa in group B was significantly increased at 4 time points compared with group A(P<0.01).After the drug intervention in group C,D and E,expression of IKKa protein was inhibited in the lung tissue of rats,with the lowest expression on the 7th day.It showed statistically significant expression of IKKα protein between group C,D,E and group B on 5th and 7th day(P<0.05).Compared with group C,the expression of IKKα protein decreased on 7th day in group E(P<0.05).7.The expression of Bcl-2 in group B was significantly lower in 5th,7th day than that in group A(P<0.05),and reached the lowest at the 5th day.There were statistically significant of Bcl-2 protein expression between C,D group and group B at four time points(P<0.05),group E and group B in 3rd,5th,7th day(P<0.05).Compared with group C,there was statistically significant of Bcl-2 protein expression in group D and E on 5th,7th day(P<0.05).Conclusions:1.Machine oil inhalation can cause acute lung injury in rats and IL-6,TNF-α,KL-6 and MIF reducedin BALF and serum.There were positive relation between the levels of inflammatory factors and KL-6 and KL-6 concentration combined with the dynamic level of inflammatory factors could reflect the severity of lung injury.2.The expression of NF-κB p65 in the lung tissue of rats after inhalation injury was consistent with the activation of relevant inflammatory factors.It shows that NF-κB p65 pathway was involved in the pathological changes of lung tissue in the early stage of inhalation injury by regulating the expression of inflammatory factors.IKKa exposure was also consistent with the activation of NF-κB p65,so it indicating that IKKa involves the NF-κB p65 signaling pathway.3.DXM showed a good protective effect on machine oil inhalation-induced lung injury,that in can ameliotatr the expression of inflammation factor and tissue inflammation.4.The mechanism of DXM against AELP in rats potentially is inhibiting the activation of NF-κB p65 and the expression of IKKa protein,as a result,it relieves tissue inflammation and reduced pathological damage to lung tissue.DXM also can up-regulate the expression of Bcl-2 and enhance the function of anti-apoptosis to reduce programmed cell death. |
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