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Objective:To evaluate the role of aryl hydrocarbon receptor (AhR) in the down-regulation of Clara cell secretory protein (CCSP) expression during endotoxin-induced lung injury in rats.Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8 weeks, weighing 200-250 g, were divided into 4 groups ( n=6 each) using a random number table method: normal control group (group C), acute lung injury (ALI) group, ALI+ AhR antagonist group, and ALI+ vehicle group. Lipopolysaccharide(LPS) 1 mg/kg was intratracheally instilled to develop the model of lung injury, while the equal volume of normal saline was given instead in group C. At 2 h before LPS injection, AhR antagonist 6, 2′, 4′-trimethoxyflavone solution 5 mg/kg (diluted to 1 ml in dimethyl sulfoxide solution) was intraperitoneally injected in ALI+ AhR antagonist group, while dimethyl sulfoxide solution 1 ml was given in ALI+ vehicle group. The rats were sacrificed under anesthesia at 48 h after LPS administration. The left lung was lavaged and the broncho-alveolar lavage fluid (BALF) was collected for determination of the concentrations of CCSP by enzyme-linked immunosorbent assay, and the expression of CCSP in the bronchial epithelium in right lung tissues was determined by immunohistochemistry. Results:Compared with group C, the expression of CCSP in the bronchial epithelium was significantly down-regulated, and the concentrations of CCSP in BALF were decreased in the other three groups ( P<0.05 or 0.01). Compared with ALI group and ALI+ vehicle group, the histopathological injury was significantly reduced, the expression of CCSP in the bronchial epithelium was up-regulated, and the concentrations of CCSP in BALF were increased in ALI+ AhR antagonist group ( P<0.01). Conclusions:AhR partially mediates the down-regulation of CCSP expression during endotoxin-induced lung injury in rats.
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Objective:To analyze the effect of lung protective ventilation on lung ventilation function and serum Clara cell protein 16 (CC16) level in patients undergoing gynecological laparoscopic surgery.Methods:The clinical data of 80 gynecological patients who underwent laparoscopic surgery in Yancheng City Jianhu County People′s Hospital from October 2018 to December 2020 were randomly divided into group A and group B by random number table, each group with 40 cases. The patients in group A were treated with intermittent positive-pressure ventilation, and the patients in group B were ventilated with whole course ventilation mode. The pulmonary ventilation function, CC16 level and postoperative pulmonary complications were observed before anesthesia, 10 min of pneumoperitoneum, 30 min of pneumoperitoneum, 5 min of pneumoperitoneum stop and 2 h after operation. The patients were divided into groups according to whether with pulmonary complications, and their pulmonary ventilation function and serum CC16 level were compared. The predictive value of the above indexes for pulmonary complications was analyzed by receiver operating characteristic (ROC) curve.Results:Repeated measurement analysis of variance showed that alveolar arterial oxygen differential pressure (PA-aDO 2) were significant differences in time point factors, time point interaction factors and group factors ( P<0.05); CC16 index were significant differences in time point factor and group factor ( P<0.05). According to the observation from postoperative to discharge, 4 patients (10.0%) in group A had pulmonary complications, 15 cases (37.5%) had pulmonary complications in group B, the levels of PA-aDO 2 and CC16 in patients with complications were significantly higher than those in patients without complications: group A:(332.9 ± 2.0) mmHg (1 mmHg = 0.133 kPa) vs. (290.4 ± 13.2) mmHg, (53.5 ± 1.5) μg/L vs. (39.5 ± 6.5) μg/L; group B: (339.1 ± 8.8) mmHg vs. (305.7 ± 17.9) mmHg, (41.5 ± 4.2) μg/L vs. (39.7 ± 5.8) μg/L, there were statistical differences ( P<0.05). ROC curve analysis showed that the area under the curve(AUC) of PA-aDO 2 and CC16 in predicting pulmonary complications in group A were 0.882 and 0.833, in group B was 0.885 and 0.731. Conclusions:Lung protective ventilation has little effect on lung ventilation function and serum CC16 in patients with gynecological laparoscopic surgery, and the probability of pulmonary complications is lower. The pulmonary ventilation function and CC16 have certain value in predicting postoperative pulmonary complications.
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Clara cell secretory protein 16(CC16)is one of the most important secreted proteins of Clara cells in respiratory epithelium, which mainly exists in the lining fluid of lung epithelial cells.When the bronchoalveolus-capillary membrane barrier is damaged, a large amount of CC16 will enter the blood.It′s eventually excreted in the urine.In recent years, more and more studies have found that CC16 not only has anti-inflammatory, immune-modulating, anti-oxidation and anti-fibrosis effects, but also is a sensitive indicator of the integrity of the airway epithelium, which can predict the occurrence and development of many children′s pulmonary diseases.This article mainly summarizes the biological characteristics and functions of CC16, and summarizes the research progress of CC16 in the diagnosis and treatment of pediatric pulmonary diseases.
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Objective:To investigate the clinical significance of changes of serum Clara cell secretory protein(CC16) and pulmonary surfactant protein A(SP-A) in neonates with acute respiratory distress syndrome(ARDS).Methods:The data of 30 neonates with ARDS who needed mechanical ventilation in neonatal intensive care unit of Xi′an Children′s Hospital from January 2016 to November 2018 were collected as observation group, including 12 cases in mild group, 10 cases in moderate group and 8 cases in severe group.The data of healthy newborns during the same period were taken as control group.The serum levels of CC16 and SP-A were detected by ELISA.The serum levels of CC16 and SP-A among different groups were compared.Results:The levels of serum CC16 and SP-A in ARDS group were (59.35±3.67)mg/L and(75.38±6.27)mg/L respectively, (11.26±1.32)mg/L and(18.15±2.69)mg/L in healthy group.The difference was significant( P<0.05). And the differences of serum CC16 and SP-A levels among different degree ARDS groups were significant( P<0.05). The levels of serum CC16 in mild, moderate and severe subgroup were(38.27±16.01)mg/L, (51.25±15.63)mg/L, (84.76±13.12)mg/L and SP-A were(47.02±7.18)mg/L, (73.12±7.98)mg/L, (96.45±12.50)mg/L, which increased with disease severity. Conclusion:Serum CC16 and SP-A are increased and correlated with the severity of neonatal ARDS, which may be used as the index for evaluating the severity of neonatal ARDS in the future.
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@#【Objective】To determine the effects of an open-lung strategy（OLS）comprising moderate positive end- expiratory pressure （PEEP） and intermittent recruitment manoeuvres（RMs） on plasma levels of lung epithelial injury markers［i.e. soluble receptor for advanced glycation end products（sRAGE）and Clara cell protein（CC16）］during low- tidal-volume ventilation for surgery.【Methods】One hundred patients who were undergoing laparoscopic colorectal cancer resection under low-tidal-volume ventilation were enrolled in this study. They were randomly assigned（1∶1）to the OLS group（using PEEP of 6~8 cmH2O and intermittent RM），or the NOLS group（without using PEEP and RM）. Blood samples were taken before anesthesia induction（T1），immediately after surgery（T2）and the postoperative day 3（T3）to measure the plasma concentrations of sRAGE and CC16. 【Results】 Significant differences were not observed in the concentrations of sRAGE and CC16 at T1，T2 and T3 between the two groups（all P > 0.05）. For all the enrolled patients， the concentrations of sRAGE at T2 and T3 were higher than that at T1，the concentration of sRAGE at T3 was higher than that at T2，and the concentration of CC16 at T3 was higher than that at T1 and T2（all P < 0.05）.【Conclusions】In patients under general anesthesia with low-tidal-volume ventilation，the using of an OLS comprising medium PEEP and intermittent RMs can not alter plasma levels of lung epithelial injury markers（sRAGE and CC16）in three days after surgery.
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Objective To investigate the clinical value of combined detection of serum angiopoietin 2 (Ang-2) and Clara cell protein 16 (CC16) in the early diagnosis of acute respiratory distress syndrome (ARDS).Methods Two hundred critical patients, treated at the Department of Critical Care Medicine, Bao'an District People's Hospital, Shenzhen during March 2015 and September 2016,were included in the study. According to the Berlin standard, patients were divided into two groups (n=100 each group): the ARDS group and non-ARDS group.The serum levels of Ang-2 and CC16 were measured by enzyme-linked immunosorbent assay (ELISA) on the first and second day of admission for each patient, in addition to completing APACHEⅡ score, medical history, vital signs collection and other biochemical indicators detection. Finally, paired-samplest test was used to analyze the data. The multiple ROC curve was used to calculate the area under the curve of the reference index of the serum levels of Ang-2 and CC16 on the first and second day.Results On the first and second day, the serum levels of Ang-2 and CC16 were significantly higher in ARDS patients than those in non-ARDS patients, and there was a correlation between the serum levels of Ang-2 and CC16 in ARDS patients. The ROC curve showed that the combined detection of Ang-2 and CC16 on the first day achieved a highest sensitivity of 75.9％ and detection of CC16 on the first day achieved a highest specificity of 70.2％. Conclusion Single-detection of serum levels of Ang-2 and CC16 could be used for early diagnosis of ARDS, and the combined detection of both has a higher sensitivity than single detection.
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Objective@#To investigate the role of E-selectin, Clara cell secretory protein 16 (CC-16), and pulmonary surfactant protein A (SP-A) in the diagnosis of neonatal ARDS.@*Methods@#Full-term newborn with ARDS in 9 hospitals of Jiangsu Province from March 1st 2015 to February 29th 2016 were selected as observation group.According to the lung oxygenation of the neonates, they were divided into three groups: mild, moderate and severe.In addition, 60 normal full-term newborns were selected as control group.In the observation group, venous blood samples were taken on the 1st, 3rd and 7th day of diagnosis and the control group within 7 days after birth.The level of E-selectin, CC-16 and SP-A were detected by double antibody sandwich enzyme-linked immunosorbent assay.The changes of the level of E-selectin, CC-16 and SP-A at different time points and in neonatus with different severity of ARDS were compare with control group and correlatively analyzed.@*Results@#The observation group included 60 newborns who met the diagnostic criteria of ARDS with male 38, female 22, day age (7.3 ±3.3) hours, gestational age (39.5 ±1.7) weeks and birth weight (3280 ±577) g. The control group included 60 normal full-term newborns, with male 30, female 30, day age (6.9 ±4.2) hours, gestational age (39.4 ±1.5) weeks and birth weight (3329 ±593) g. There was no significant difference between two groups.The levels of E-selectin[1 d, 3 d, 7 d: (36.36 ±8.32)μg/L, (45.51 ±9.26)μg/L, (57.15 ±6.84)μg/L], CC-16[1 d, 3 d, 7 d: (25.24 ±8.63)mg/L, (48.33±10.83)mg/L, (18.84±10.11)mg/L]and SP-A [1 d, 3 d, 7 d: (58.38±10.31)mg/L, (53.29±11.31)mg/L, (25.99±6.66)mg/L]in the blood of the observation group increased on the first day and reached the peak on the third day, which were significantly higher than those in the control group [E-selectin, CC-16, SP-A: (15.52 ±6.24)μg/L, (11.26 ±5.18)mg/L, (24.30 ±5.27)mg/L] (P<0.05). The levels of E-selectin [mild, moderate, severe are(30.07±6.10)μg/L, (33.39 ±6.64)μg/L, (41.63 ±7.36)μg/L], CC-16 [mild, moderate, severe are(12.61 ±5.80)mg/L, (25.22 ±6.77)mg/L, (30.61 ±4.69)mg/L]and SP-A [mild, moderate, severe are(49.67 ±8.26)mg/L, (7.11 ±7.94)mg/L, (63.19 ±11.45)mg/L]increased gradually in the blood of ARDS neonates with different severity (P<0.05), especially in moderate and severe degree.There was a significant negative correlation between E-selectin (r=-0.629 8), CC-16 (r=-0.679 3), SP-A (r=-0.458 8) and PaO2/FiO2 (P<0.05).@*Conclusion@#The levels of E-selectin, CC-16 and SP-A in the blood of ARDS neonates increased significantly and were closely related to the severity of the disease, which may be a biomarker of neonatal lung injury.
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Objective@#To investigate the clinical value of combined detection of serum angiopoietin 2 (Ang-2) and Clara cell protein 16 (CC16) in the early diagnosis of acute respiratory distress syndrome (ARDS).@*Methods@#Two hundred critical patients, treated at the Department of Critical Care Medicine, Bao'an District People's Hospital, Shenzhen during March 2015 and September 2016,were included in the study. According to the Berlin standard, patients were divided into two groups (n=100 each group): the ARDS group and non-ARDS group.The serum levels of Ang-2 and CC16 were measured by enzyme-linked immunosorbent assay (ELISA) on the first and second day of admission for each patient, in addition to completing APACHEⅡ score, medical history, vital signs collection and other biochemical indicators detection. Finally, paired-samples t test was used to analyze the data. The multiple ROC curve was used to calculate the area under the curve of the reference index of the serum levels of Ang-2 and CC16 on the first and second day.@*Results@#On the first and second day, the serum levels of Ang-2 and CC16 were significantly higher in ARDS patients than those in non-ARDS patients, and there was a correlation between the serum levels of Ang-2 and CC16 in ARDS patients. The ROC curve showed that the combined detection of Ang-2 and CC16 on the first day achieved a highest sensitivity of 75.9% and detection of CC16 on the first day achieved a highest specificity of 70.2%.@*Conclusion@#Single-detection of serum levels of Ang-2 and CC16 could be used for early diagnosis of ARDS, and the combined detection of both has a higher sensitivity than single detection.
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Objective To observe the changes of serum clara cell protein?16 ( CC?16 ) and monocyte chemotaxis protein?1 (MCP?1) level in patients with acute respiratory distress syndrome (ARDS) and to explore their relationship with the disease severity and prognosis of ARDS??Methods One hundred and fourteen patients with ARDS who were admitted to Changzhi People′s hospital from January 2017 to March 2018 were selected as the subjects??They were divided into mild group ( n＝37),moderate group (n＝41) and severe group ( n＝36) according to the severity of ARDS??Sixty healthy persons in out?patient examination were selected as control group??The survival situation of patients in 4 weeks were recorded,the patients were divided into survival group ( n＝65) and death group ( n＝49) according to their survival situation??The age,gender,body mass index (BMI),smoking history,acute physiology and acute physiology and chronic health evaluation II ( APACHE II) score,sequential organ failure assessment ( SOFA) score, serum CC?16 and MCP?1 level were analyzed in each group??The relationship between serum CC?16,MCP?1 level and disease and prognosis of patients with ARDS were analyzed??Results With the increase of disease severity,APACHE II score, SOFA score and serum CC?16, MCP?1 level in patients with ARDS were significantly increased??The differences were statistically significant ( F＝1 216??886,1 339??247,290??879, 417??262; all P＝0??000)??The APACHE II score,SOFA score and serum CC?16,MCP?1 levels in the death group were (22??13± 2??47) scores,( 15??09 ± 1??97) scores,( 23??85 ± 4??27) μg／L, ( 36??64 ± 5??21) ng／L respectively,which were significantly higher than those in the survival group (18??25±2??35) scores,(13??23 ±2??03) scores,(17??34±4??13) μg／L,(27??93±4??88) ng／L,the differences were statistically significant (t＝8??538,4??905,8??211,9??146;all P＝0??000)??Pearson correlation analysis showed that there was a positive correlation between serum CC?16 level and MCP?1 level in patients with ARDS ( r＝0??589, P ＝0??000)??Meanwhile,the CC?16,MCP?1 were positive correlation with APACHE II score,SOFA score and mortality (CC?16:r＝0??504,0??549,0??472;P＝0??000,0??000,0??012;MCP?1:r＝0??493,0??528,0??435;P＝0??006, 0??000,0??025)??APACHE II score ( OR＝3??083,95%CI:0??025－1??364,P＜0??05),CC?16 ( OR＝5??403, 95%CI:0??011－6??561, P＜0??05) and MCP?1 ( OR＝2??892, 95%CI: 0??034－1??619, P＜0??05) were all closely related to ARDS death??CC?16 independent detection, MCP?1 independent detection and the two combined detection predicted the under?curve area, sensitivity and specificity of ARDS patients with in 4 weeks were 0??830, 82??35% and 72??16%; 0??719, 79??25% and 72??19%; 0??866, 85??06% and 80??72%respectively??Conclusion CC?16,MCP?1 are abnormally high expression in serum of patients with ARDS, and its levels are closely related to the severity and prognosis of patients with ARDS??CC?16 combined with MCP?1 detection has high diagnostic value for patients with ARDS,which can be used as an effective index to judge the disease and prognosis of patients with ARDS??
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Objective@#To investigate the effects of long-term exposure to silica dust on serum CC16 and KL-6 levels.@*Methods@#The patients with stage I silicosis who were hospitalized in our hospital from April 2016 to April 2017 were treated as silicosis group. The silica dust exposed workers without silicosis who were taken the physical examination in our hospital were taken as a dust-exposed group. The healthy control group comes from in the same period of community physical examination did not touch the dust. The levels of CC16 and KL-6 in serum of all subjects were determined by enzyme-linked immunosorbent assay (ELISA) , and the levels of CC16 and KL-6 in serum were compared in three groups.@*Results@#Compared with the control group, the serum levels of CC16 in the silicosis group (P<0.01) and the dust-exposed group (P<0.01) were significantly lower. Compared with the control group, the level of serum KL-6 in the silicosis group was significantly decreased (P<0.01) compared with the control group, while the level of KL-6 in the serum of the dust-exposed group was significantly increased (P<0.01) . The ROC area of CC16 for diagnosis of silicosis was 0.92 (P<0.01) , with a sensitivity of 81.37%, specificity of 92.63% and Kappa value of 0.74.@*Conclusion@#Long-term exposure to silica dust may lead to a decrease in serum CC16 levels. Reduced serum CC16 levels may be useful in identifying the diagnosis of silicosis.
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OBJECTIVE: To study the method and significance of serum level of Clara cell protein(CC16) and surfactant protein D(SP-D) in the early diagnosis of patients with occupational silicosis. METHODS: By a convenience sampling method, 73 male patients with occupational silicosis were included in the silicosis group, 27 male workers who exposed to dust without occupational silicosis were selected as the dust exposure group, and 27 healthy men with no history of occupational dust exposure were selected as control group. The levels of serum CC16 and SP-D were detected by enzyme-linked immune sorbent assay. RESULTS: Serum levels of CC16 in patients of silicosis and dust exposure groups were significantly lower than those of the control group [(40.15±13.31) vs(53.85±11.45) mg/L,(25.2±48.18) vs(53.85±11.45) mg/L, P<0.05]. The serum level of CC16 in silicosis group was higher than that of dust exposure group [(25.24±8.18) vs(40.15±13.31) mg/L, P<0.05]. Serum level of SP-D in silicosis group was significantly higher than those in the controls and dust exposure group [(59.22±10.67) vs(49.07±9.72) mg/L,(59.22±10.67) vs(46.82±10.40) mg/L, P<0.05]. Bayes discrimination analysis was used to establish a combined diagnostic discriminant model with age, CC16 and SP-D levels. The correct rates for the control group, the dust exposure group and the silicosis group were 100.0%, 59.3% and 83.6%, respectively, and the classification accuracy was 81.9%. The discrimination effect is good. Based on the length of service, age, CC16 and SP-D levels, the Bayes discriminant analysis was used to establish a combined diagnostic discriminant model. The correct rates of the dust exposure and silicosis groups were 100.0% and 91.8%, respectively, and the classification accuracy was 94.0%. CONCLUSION: Bayes discriminant analysis combined with serum level of CC16 and SP-D is useful for the early diagnosis of occupational silicosis and improve the diagnostic accuracy.
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Objective To explore the changes of serum Clara cell secretory protein 16 (CC16), pulmonary surfactant protein D (SP-D) in children with pneumonia and its clinical significance. Methods A total of 81 pediatric patients with community-acquired pneumonia were selected, including severe pneumonia with mechanical ventilation group (n=21), severe pneumonia with non-mechanical ventilation group (n=30), mild pneumonia group (n=30), and the control group (n=20) was selected in the physical examination of healthy children over the same period. We detected the concentration of serum CC16, TNF-α, IL-6 and SP-D for the 4 groups by ELISA, and evaluated the clinical values of serum CC16, TNF-α, IL-6 and SP-D for severe pneumonia by using ROC curve.We recorded pulmonary dynamic compliance(Cdyn),airway resistance(Raw),peak inspiratory pressure (PIP), work of breathing (WOB) and other respiratory mechanical parameters, and analyzed the correlations between CC16 and TNF-α, IL-6, SP-D and respiratory mechanical parameters. Results The concentrations of serum CC16 in pneumonia group were all significantly lower than that in the control group, and those in severe pneumonia groups were lower than that in mild pneumonia group, and mechanical ventilation group was lower than that in non-mechanical ventilation; the concentration of serum TNF-α, IL-6 and SP-D in pneumonia groups were all obviously higher than that in the control group, and severe pneumonia group were higher than that in mild pneumonia group, and those in mechanical ventilation group were also higher than that in non-mechanical ventilation group (P<0.05). Compared to that before removing the ventilator, concentration of serum CC16 in severe pneumonia with mechanical ventilation group decreased significantly at 1 hour and lowered down at 72 hours; but the concentration of serum TNF-α, IL-6 and SP-D in severe pneumonia with mechanical ventilation increased significantly at 1 hour and went higher at 72 hours, the differences were all statistically significant (all of P<0.05); compared to that before weaning from the ventilator, the value of Cdyn decreased obviously in severe pneumonia with mechanical ventilation at 72 hours and lowered down at 1 hour; but the values of Raw, PIP, WOB in severe pneumonia with mechanical ventilation increased obviously at 72 hours and more higher at 1 hour, the differences were all statistically significant (all of P<0.05). The concentration of serum CC16 showed all negative correlations with TNF-α, IL-6 and SP-D, but it showed positive correlation with Cdyn(all of P<0.01).In the ROC curve,the area under the ROC curve of CC16,TNF-α,IL-6 and SP-D in serum was 0.905, 0.704, 0.832, 0.825, respectively (for all of which P<0.01). Conclusion The concentrations of serum CC16 and SP-D were associated with the severity of community acquired-pneumonia in children. The level of serum CC16 was positive associated with Cdyn in children with mechanical ventilation. CC16 has better prediction and evaluation effect on the change of severe pneumonia.
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Objective To observe the expression of protein AQP5 and CC16 in lung after hemorrhagic shock resuscitation in rats in order to explore the mechanism of acute lung injury.Methods Thirty-two healthy and clean male SD rats were randomly (random number) divided into two groups:control group and hemorrhagic shock resuscitation group (n =16 in each).Besides,each group was further divided into two subgroups according to the experiment done at 12 h and 24 h after hemorrhagic shock resuscitation (n =8).The hemorrhagic shock model was made by using Wiggers' modified method.Resuscitation was done by transfusing the autologous blood and the equal volume of Ringer's solution.Blood samples were obtained from abdominal aorta at each given interval to measure the level of plasma endotoxin,and assay the CC16 and AQP5 by using ELISA.After the rats were sacrificed,the left lung tissue was taken to measure lung water content and the dry/wet ratio,and to examine the levels of CC16 and AQP5 in lung tissue by immunohistochemical method.Results ①The level of plasma endotoxin in the experimental group was significantly higher than that in the control group (P ＜ 0.01).②The content of plasma CC16 in the experimental group was higher than that in the control group (P ＜ 0.05).③Compared with the control group,the content of pulmonary homogenate AQP5 in the experimental group was significantly lower (P ＜0.05).④The lung water content (the dry/wet ratio) of the experimental group was obviously higher than that of the control group (P ＜ 0.05).⑤Hislogogical observation with HE staining showed in the control group,the alveolar structure was complete,the alveolar sacs were clear,and the alveolar septum was intact;but in the experimental group,the alveolar septum was widened,and there were obvious hemorrhage and neutrophil infiltration in the alveolar space.⑥ The level of lung tissue CC16 in control group was significantly higher compared with experimental group (P ＜ 0.05).⑦ The level of lung tissue AQP5 was significantly higher in control group compared with experimental group (P ＜ 0.05).Conclusions The proteins of AQP5 and CC16 were involved in the process of acute lung injury after hemorrhagic shock resuscitation in rats,and their levels were positively correlated with length of time after hemorrhagic shock.
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Objective To evaluate the effect of dexmedetomidine pretreatment on expression of se-cretion protein of Clara cell secretory protein(CC16)during endotoxin-induced acute lung injury(ALI) in rats.Methods One hundred and twelve healthy Wistar rats of both sexes, aged 8-12 weeks, weighing 250-350 g, were divided into ALI group(n=56)and dexmedetomidine pretreatment group(group DEX, n= 56)using a random number table.ALI was induced by intravenously injecting lipopolysaccharide (LPS)5 mg∕kg over 1 min.Dexmedetomidine 10 μg∕kg was intravenously infused over 10 min starting from 10 min before LPS in group DEX.At 10 min before LPS injection and 0.5, 1, 2, 4, 6 and 24 h after LPS injection, 8 rats were sacrificed and lungs were removed for examination of the pathological changes(with a light microscope)and ultrastructure of Clara cells(with a transmission electron microscope)and for deter-mination of CC16 expression in bronchioles(by immunohistochemistry). Results Compared with the baseline at 10 min before LPS injection, the expression of CC16 in bronchioles was significantly down-regu-lated at 1, 2, 4, 6 and 24 h after LPS injection in group ALI and at 1, 2, 4 and 6 h after LPS injection in group DEX(P<0.01), the pulmonary small arterial hyperemia, alveolar septa edema, red blood cell exudation and inflammatory cell infiltration were found, the Clara cells in bronchioles were reduced, the secretory granules in the cytoplasm were reduced, and the mitochondria were swollen and deformed after in-jection of LPS.Compared with group ALI, the expression of CC16 in bronchioles was significantly up-regu-lated at 1, 2, 4, 6 and 24 h after LPS injection(P<0.01), the pathologic changes of lung tissues were significantly attenuated, and the number of Clara cells was increased in group DEX.Conclusion The mechanism by which dexmedetomidine pretreatment reduces endotoxin-induced ALI may be related to up-regulating CC16 expression in rats.
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Objective To study the change and clinical value of SP‐D ,CCL18 and CC16 in serum and in exhaled breath con‐densate in acute exacerbation of chronic obstructive pulmonary disease .Methods Sixty two cases of COPD patients admitted in our hospital from 2010 January to 2013 December were selected as the research object .All the 62 patients were divided into group A(32 patients with COPD in acute exacerbation) and group B(30 patients with COPD in remission stage) in accordance with the severity of COPD .Thirty six cases of health people were selected as the control group .Statistical subjects SP‐D ,CCL18 ,CC16 content in se‐rum and in exhaled breath condensate ,and the relations between the various indexes and age ,smoking ,pulmonary function and BMI were analyzed .Results The exhaled breath condensate SP‐D ,CCL18 content in group A was significantly higher than that of B group and the control group (P<0 .05) ,and the SP‐D ,CCL18 in group B was higher than that in control group (P<0 .05) .The se‐rum SP‐D ,CCL18 ,CC16 content in group A was significantly higher than that of B group and the control group (P<0 .05) ,and the SP‐D ,CCL18 ,CC16 in group B was higher than that in control group (P< 0 .05) .Serum SP‐D ,CCL18 levels were significantly higher than those in the exhaled breath condensate (P< 0 .01) .Exhaled breath condensate SP‐D was positively associated with smoking age (r=0 .298 ,P<0 .05) ,and FEV1% pred ,FEV1/FVC (% ) showed a negative correlation (r= -0 .318 ,-0 .402 ,P<0 .05);the serum levels of SP‐D was positively associated with tobacco (r=0 .297 ,P<0 .05) ,and FEV1% pred ,FEV1/FVC (% ) were negative correlated (r= -0 .278 ,-0 .298 ,P<0 .05);serum CC16 and FEV1% pred ,FEV1/FVC (% ) were negatively corre‐lated (r= -0 .358 ,-0 .382 ,P<0 .05);Exhale breath condensate SP‐D ,condensate CCL18 ,SP‐D ,CCL18 serum ,serum CC16 were are positively correlated in each two (P<0 .05);and there was no significant correlation between other indexes and age ,smoking , pulmonary function and BMI etc .Conclusion Exhaled breath condensate ,serum SP‐D ,serum CCL18 ,exhaled breath condensate , exhaled breath condensate ,serum CC16 are closely related to acute exacerbation of COPD ,and monitoring the indicators can be judgment of the degree and prognosis of COPD .
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Objective To determine the effects of intrauterine growth retardation(IUGR) caused by malnutrition during pregnancy on the lung structure and expression of Clara cell protein (CCSP) and interferon (IFN)-γ in the fetal lungs,and to explore their relation ship with pulmonary disease.Methods Fetal rats from maternal protein-malnutrition dams were studied on day 20(term 21.5 day).The lung pathology was examined by means of Hematoxylin and eosin(HE) stain.Plasma was collected to determine the CCSP and IFN-γ concentration.Lungs were harvested to measure the expression of CCSP and IFN-γ mRNA by using fluorescent quantization reverse transcription (RT)-PCR and the levels of CCSP and IFN-γ protein were assessed by using enzyme-linked immunosorbent assay.Results Malnutrition fetus body weight significantly less compared to control group,so did the lung weight.However,lung weight,expressed as a percentage of body weight between the 2 groups was not different.The IUGR group had significantly decreased alveolar number manifested by lower radial alveolar count,and significantly increased mean linear intercept of alveoli.Both the CCSP mRNA expression and protein level in lung of IUGR rats were decreased compared with control rats (all P ＜ 0.05).A decline in plasma CCSP protein concentration was also noted compared with control group (P ＜0.05).Furthermore,IUGR group fetus showed lower IFN-γ levels both in circulation and in the lung tissue (all P ＜ 0.05).Conclusions Intrauterine malnutrition significantly alters lung structure and cytokine IFN-γ level,and the latter may further inhibit the transcription of CCSP gene.These alterations may contribute to both early and late postnatal respiratory morbidity.
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Objective To investigate the effect and mechanism of Clara cell secretory protein (CC16 ) on lung injury of traumatic shock rats.Methods Thirty SD male rats were randomly assigned to three groups:sham-operation group,control group and CC16-treatment group.The rat model of traumatic shock was used in this study.Rats of sham-operation group were operated,but not treated by depletion and recovery.Rats of control group inhaled the physiological saline before fluid resuscitation.Rats of CC16-treatment group inhaled 0.1 μg/mL of recombinant human Clara cell secretory protein (rh-CCSP)before fluid resuscitation.Arterial blood gas analysis and wet/dry weight were detected in each group.The contents of malondialdehyde (MDA),myeloperoxidase (MPO)of lung tissues and lung tissue pathology changes were also studied. Results Compared with control group,pH and PaO2 value in CC16-treatment group increased significantly.Meanwhile,BE value and lung wet/dry weight ratio also decreased significantly (P<0.05).Compared with control group,contents of MDA and MPO in CC16-treatment group decreased significantly (P<0.05).Lung tissue pathology improved in the CC16 group compared with that of control group (P <0.05 ).Conclusion Inhaled Rh-CCSP may have potential protective effect on lung injury tissues of traumatic shock rats model through its antioxidative effect.
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Objective To explore the clinical value of clara cell protein 16 (Cc 16) in the early diagnosis of ARDS in critically ill patients.Methods A total of 55 critically ill patients admitted between March 2013 and December 2013 in the Intensive Care Unit were enrolled for study.The inclusion criteria were as follows:sepsis,pneumonia,multiple injuries,patients after emergency or elective operation and non-cardiogenic diseases,whereas the exclusion criteria were cardiogenic pulmonary edema,age ≤ 18 years or≥80 years and disease course prolonged over one week.The level of serum Cc16 was detected with enzyme linked immunosorbent assay (ELISA).In addition,data of other biochemical examinations,the Acute Physiology and Chronic Health Evaluation (APACHE]Ⅱ) score and the relevant medical data were documented.The patients were divided into ARDS groups and non-ARDS groups based on clinical data met Berlin definition.Results The sensitivity and specificity of serum Cc16 for diagnosis of ARDS were 92％ and 80％,respectively with the area under the curve being 0.92,which were better than those of APACHE Ⅱ score,D-dimer,C-reactive protein,N-terminal pro-brain natriuretic peptide and serum albumin detected by the means of receiver operating characteristic curve,and cut off value was 20.62 ng/L.The bivariate analysis showed there was negative correlation between Cc16 and oxagenation index in ARDS patients and the Pearson correlation coefficient of serum Cc16 with oxygenation index was r =-0.342 (P =0.04).The results of one-way analysis of variance showed difference in level of Cc16 between subgroups (F =15.76,P =0.005 17).The level of Ccl6 in severe ARDS group was (64.18 ± 12.95) ng/L which was higher than that in mild ARDS group (35.87 ± 11.28) ng/L (P =0.001 14),and in moderate ARDS group (38.66 ± 20.14) ng/L (P =0.004 9),and in non-ARDS group (16.72 ± 8.74) ng/L (P =0.000 32).There was no statistically significant difference in Cc16 level between mild ARDS group and moderate ARDS group (P =0.682).The level of serum Ccl6 did not correlate with type or days of respiratory ventilation support,28-day survival rate or 120-hour survival rate and days of ICU stay and hospital stay.Conclusions The diagnostic value of serum Cc16 is very high in determining the presence and severity of ARDS in addition to the Berlin criteria in critically ill patients accurately assessing degree of lung injury.
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Objective To explore the anti-inflammatory effect of antiflammin-2 (AF2) and recombinant peptide sequence 2(R2) on acute lung injury of mouse. To observe the expression of clara cell 16000 protein (CC16) and surfactant protein A (SP-A) in the lung of mouse inoculated with lipopolysaccharide (LPS) and the impact of AF2,R2,and glucocorticoids(hydrocortisone,HC) may have on the expression of the CC16 and SP-A in the lung of mice with acute lung injury. Methods Balb/c mice were inoculated with LPS (5 mg/kg) by intraperitoneal injection to set up ALI mice model. Mice weighed from 15 g to 16 g were grouped into control group, model group and treated groups respectively treated with AF2, R2 or HC. Mice in the control group were injected with physiological saline solution, while mice in the other four groups were inoculated with LPS to induce acute lung injury. Then animals in the treated groups were treated with AF2, R2 or HC each on a dose of 2 mg/kg also through intraperitoneal injection,while those of the control group and the model group, were given equivalent physiological saline solution as a placebo. The respiratory rate of all of these animals were recorded 6 hours after the injection. And at the time point of 12 hour,all the mice were sacrificed for a preparation of the whole lung tissue for the sake of a pathological investigation ,or for extractions of RNA for a semiquantitative analysis of the expression of CC16 and SP-A within the lungs. Results (1) An obvious attenuation of the respiratory rates of the three treated groups were observed when comparing with that of the mice in the model group without any anti-inflammatory treatment. (2) Remarkable extenuation of the extent of intra-alveolar and intersticial hemorrhage and infiltration of inflammatory cells were observed within the treated groups comparing with that of the model group. (3) An attenuate expressions of CC16 or SP-A were observed in the model group,while obvious uptrend of CC16 expression was observed in AF2 treated groups and increase of SP-A expressions were found in R2 and HC treated groups. Conclusion The anti-inflammatory effect of the peptide, AF-2 or R2, has been conformed on ALI mice model induced by LPS.
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Conventional lung cancer therapies are associated with poor survival rates; therefore, new approaches such as gene therapy are required for treating cancer. Gene therapies for treating lung cancer patients can involve several approaches. Among these, aerosol gene delivery is a potentially more effective approach. In this study, Akt1 kinase-deficient (KD) and wild-type (WT) Akt1 were delivered to the lungs of CMV-LucR-cMyc-IRES-LucF dual reporter mice through a nose only inhalation system using glucosylated polyethylenimine and naphthalene was administrated to the mice via intraperitoneal injection. Aerosol delivery of Akt1 WT and naphthalene treatment increased protein levels of downstream substrates of Akt signaling pathway while aerosol delivery of Akt1 KD did not. Our results showed that naphthalene affected extracellular signal-regulated kinase (ERK) protein levels, ERK-related signaling, and induced Clara cell injury. However, Clara cell injury induced by naphthalene was considerably attenuated in mice exposed to Akt1 KD. Furthermore, a dual luciferase activity assay showed that aerosol delivery of Akt1 WT and naphthalene treatment enhanced cap-dependent protein translation, while reduced cap-dependent protein translation was observed after delivering Akt1 KD. These studies demonstrated that our aerosol delivery is compatible for in vivo gene delivery.