Investigation of control region sequences of mtDNA in Naqu Tibetan population from Northwestern China.

BACKGROUND: The sequence polymorphisms of mitochondrial DNA (mtDNA) are valuable in forensic medicine and anthropological genetics. AIM: We analysed the sequences of the mtDNA control region in 207 unrelated Tibetan individuals from the Naqu region, Tibet Autonomous Region in the People's Republic of China, and investigated the population structure of the region by population comparison with other groups. SUBJECTS AND METHODS: Genomic DNA was extracted and hypervariable regions (HVS-I and HVS-II) were amplified and sequenced. Subsequently, sequences were aligned and compared with the revised Cambridge sequence. Moreover, population comparison was performed between the Naqu Tibetan group and the other groups. CONCLUSION: Our study provided available data for exploring the mtDNA haplotype of the Tibetan population in the Naqu region, and population comparisons found that the Naqu Tibetan population has its own unique structure.

[Interpretation of the disaster response plans in the pediatric intensive care unit].

In April 2018, the Group of Pediatric Disasters, Pediatric Society, Chinese Medical Association and Pediatric Committee, Medical Association of Chinese People's Liberation Army issued the disaster response plans in the pediatric intensive care unit (PICU). This article outlines the development of the plans and the implementation of PICU disaster rescue, along with ethical issues in the context of disasters and psychological reconstruction after a disaster.

A Clinical Study of Toxication Caused by Carbamazepine Abuse in Adolescents.

Carbamazepine is known to produce the side effect of euphoria. As such, it lends itself to being a drug of abuse, particularly in the adolescent population. This retrospective study evaluated carbamazepine abuse, treatment course, and associated morbidity in Chinese adolescents. The median dose of carbamazepine resulting in overdose was 2,000 mg (800-5,000). Patients were largely from urban-rural fringe areas (76.47%, 52.94%) with school performance within the last 1/3 range and (52.94%) unsupervised by parents. 35.29% experienced an obvious sense of euphoria. All patients had nervous system symptoms, 6 (35.29%) cases developed coma (GCS < 8), and 5 (29.41%) cases experienced convulsion. Four cases were treated with hemodialysis. The incidence rate in young patients with repeat carbamazepine use and without the supervision of parents was higher than that in first-time users (5/7 versus 4/10), but the difference was not significant. The toxic dose of repeat users was 3428 ± 1035 mg, significantly higher than that of 1470 ± 646 mg in first-time users (P = 0.001). Carbamazepine can produce a sense of euphoria, which is more likely to lead to its abuse and overdose in adolescents. To prevent carbamazepine abuse and overdose will be critical in educating at-risk adolescents and preventing associated morbidities in the future.

[Relationship between fever degree and prognosis in children with bacterial bloodstream infection].

OBJECTIVE: To study the relationship between the degree of fever within 48 hours of admission and the prognosis in children with bacterial bloodstream infection. METHODS: This study retrospectively analyzed the clinical data of all patients diagnosed with sepsis who were admitted to the pediatric intensive care unit (PICU) of Shengjing Hospital Affiliated to China Medical University between September 2008 and September 2016. The children with bacterial bloodstream infection were classified into 5 groups according to the maximum temperature within 48 hours of admission: <36.5°C group, ≥36.5°C group (normal control), ≥37.5°C group, ≥38.5°C group, and ≥39.5°C group. The mortality was compared between the five groups. Results A total of 213 children with bacterial bloodstream infection were enrolled, consisting of 5 cases in the <36.5°C group, 44 cases in the ≥36.5°C group, 73 cases in the ≥37.5°C group, 69 cases in the ≥38.5°C group, and 22 cases in the ≥39.5°C group. A total of 48 cases died among the 213 patients. A significant difference was observed in the mortality between the five groups (P<0.01). The <36.5°C group and ≥39.5°C group had significantly higher mortality than the normal control group. However, there were no significant differences in the mortality between the ≥37.5°C and ≥38.5°C groups and the normal control group. Conclusions In children with bacterial bloodstream infection, those with a maximum temperature below 36.5°C or above 39.5°C within 48 hours of admission have a significantly increased mortality.

[Risk factors for multidrug-resistant Klebsiella pneumoniae sepsis in children].

OBJECTIVE: To explore the risk factors for sepsis caused by multidrug-resistant Klebsiella pneumonia (MDR-KP) and to provide a reference for the prevention of MDR-KP sepsis and rational use of antibiotics. METHODS: A retrospective case-control study of 41 children with MDR-KP sepsis (case group) and 53 pediatric patients without MDR-KP sepsis (control group) between March 2010 and Febrary 2014 was conducted. Multiple logistic regression analysis was performed to estimate the independent risk factors for MDR-KP sepsis. RESULTS: Compared with the control group, the case group had a longer length of stay in the PICU before infection (P<0.05), more prolonged duration of mechanical ventilation before infection (P<0.05), a larger total number of days of mechanical ventilation (P<0.05), more days of antibiotic use before infection (P<0.05), more types of antibiotics used before infection (P<0.05), and a higher mortality (P<0.05). The logistic regression analysis showed that more types of antibiotics used before infection and use of third-generation cephalosporin and carbapenems were independent risk factors for MDR-KP sepsis (P<0.05). CONCLUSIONS: Rational use of antibiotics is an effective measure to prevent MDR-KP sepsis.

[Investigation of disease spectrum in the PICU of Shengjing Hospital of China Medical University between 2005 and 2012].

OBJECTIVE: To summarize the spectrum of disease and common diseases that cause death in children admitted to the Pediatric Intensive Care Unit (PICU), Shengjing Hospital of China Medical University between 2005 and 2012. METHODS: A retrospective analysis was carried out on the clinical data of 4484 children admitted to the PICU of Shengjing Hospital between 2005 and 2012. RESULTS: Acute bronchopneumonia, which was found in 1099 (24.51%) of the 4484 cases, was the most common disease in the PICU between 2005 and 2012. The incidence of intracranial infection, sepsis, hand-foot-mouth disease and trauma showed an increasing trend from 2005 to 2012, but that of non-traumatic intracranial hemorrhage, epilepsy and congenital heart disease showed a decreasing trend. The mortality decreased from 11.5% in 2005 to 3.1% in 2012, and the overall mortality was significantly higher in 2005-2008 than in 2009-2012 (11.98% vs 4.41%; P<0.01). The main causes of death included severe acute bronchial pneumonia, severe sepsis, complex congenital heart disease, severe cerebral trauma, respiratory failure, severe hand-foot-mouth disease, acute poisoning and circulatory failure. CONCLUSIONS: Acute bronchopneumonia was the most common disease in the PICU of Shengjing Hospital between 2005 and 2012, but the spectrum of disease changed over time. The mortality showed a decreasing trend among the children in the PICU between 2005 and 2012, and the main causes of death included severe acute bronchial pneumonia and severe sepsis.

[Diagnostic value of serum CRP and procalcitonin levels in children with bloodstream infection-associated sepsis and septic infection at other sites].

OBJECTIVE: To evaluate the diagnostic value of measuring serum C-reactive protein (CRP) and procalcitonin (PCT) levels, within 6 hours after admission to the pediatric intensive care unit (PICU) in children with bloodstream infection (BSI)-associated sepsis and septic infection at other sites. METHODS: A retrospective analysis was performed on 30 children with a confirmed diagnosis of systemic inflammatory response syndrome who were admitted to the Shengjing Hospital of China Medical University between January 2010 and January 2012. Clinical data on serum CRP, PCT and D-dimer levels were collected within 6 hours after admission. The diagnostic values of the indices were determined by comparative analysis. RESULTS: Serum CRP and PCT levels in children with BSI-associated sepsis were significantly higher than in children with septic infection at other sites (P<0.05), but there was no significant difference in serum D-dimer levels between the two groups (P>0.05). Serum PCT level was superior to serum CRP level in distinguishing children with BSI-associated sepsis from those with septic infection at other sites. Serum PCT level could not realistically be used for diagnosing BSI-associated sepsis when it was less than 2 ng/mL (negative predictive value: 100%), but could be reliably used when it was more than 10 ng/mL (positive predictive value: 77%). CONCLUSIONS: Serum PCT level is superior to serum CRP level in distinguishing children with BSI-associated sepsis from those with septic infection at other sites within 6 hours after admission to the PICU. Serum PCT level has a better diagnostic value for BSI-associated sepsis when it is more than 10 ng/mL.

Findings in children severely infected with a novel influenza A virus of swine origin: pulmonary imaging.

BACKGROUND: This article reviews the chest radiography of children with severe infection caused by a novel influenza A (H1N1) virus of swine origin (S-OIV). We analyzed the role of their pulmonary images in predicting the severity and diagnosis of the disease. METHODS: Among 97 patients with confirmed novel H1N1 infection, 42 patients treated with mechanical ventilation formed group 1, and the remaining 55 patients constituted group 2. The initial and subsequent radiograhic findings in groups 1 and 2 were compared with respect to the pattern, distribution, and extent of the abnormality. RESULTS: In group 1, 24 patients presented with three or more lung zone diseases, whereas only 5 patients in group 2 demonstrated these findings (P<0.001). A pneumomediastinum or pneumothorax was observed in 24/42 patients in group 1 and in 18/55 patients in group 2 (P=0.019). Twelve patients in group 1 and 5 in group 2 developed a ground-glass opacity cyst with a honeycomb appearance (P=0.007). CONCLUSIONS: The most common radiographic and computed tomography findings in children who were severely infected with S-OIV included unilateral or bilateral ground-glass opacities with or without associated focal or multifocal areas of consolidation. Children with bilateral involvement or with greater opacity on the chest radiographs were more likely to worsen and require the mechanical ventilation.

[Characteristics of circulatory disturbance and the treatment of severe hand-foot-and-mouth disease].

OBJECTIVE: To investigate the characteristics of circulatory disturbance and treatment of severe hand-foot-and-mouth disease (HFMD). METHOD: The clinical characteristics, laboratory findings, therapy and outcome of 22 severe HFMD patients were retrospectively analyzed. RESULT: All the 22 severe HFMD patients came from the countryside. All these patients had encephalitis. Fifteen cases had myocardial injury. All had symptoms of sympathetic excitation and 17 cases had hypertension [(128 ± 16)/(81 ± 14) mm Hg (1 mm Hg = 0.133 kPa)]. Fourteen cases had exacerbation with rapid decline of blood pressure [(61 ± 12)/(33 ± 12) mm Hg]. In cardiorespiratory failure stage, 13 patients had neurogenic pulmonary edema accompanied by circulatory failure and 12 cases had a lower glasgow scores (less than 7). Myocardial injury and ECG change were found in some cases. Inotropic and pressor drugs were given in patients with circulatory collapse. Five cases received fluid resuscitation due to refractoriness to inotropic drugs. Nine patients received blood purification. Seventeen survived and 5 cases died due to circulatory failure. CONCLUSION: Circulation failure of severe HFMD is the main cause of death. Early and appropriate circulation support is very important to reduce mortality.

[Correlation between the blood serum BNP level and the left cardiac function in children with congenital heart disease].

OBJECTIVE: To study the correlation between the blood serum brain natriuretic peptide (BNP) level and the left cardiac function in children with congenital heart disease (CHD). METHODS: The clinical data of 41 CHD children were retrospectively analyzed. Patients were divided into two groups based on the existence of congestive heart failure (CHF): CHD+CHF (n=21) and CHD alone (n=20). The blood serum BNP level was determined using chemiluminescence immunoassay, and the left ventricular ejection fraction (LVEF) was measured with echocardiogram. RESULTS: The serum BNP level was 1353 pg/mL (range: 926-2978) in the CHD+CHF group, which was significantly higher than in the CHD alone group[149 pg/mL (range: 75-242)] (P<0.01). The LVEF was 60% (range: 53%-65%) in the CHD+CHF group, which was significantly lower than in the CHD alone group[68% (range: 64%-72%)] (P<0.01). The serum BNP level showed a negative correlation with the LVEF level (r=-0.652, P<0.01). CONCLUSIONS: The blood serum BNP level is related to the cardiac function. For children with severe CHD+CHF, serum BNP level can be used as a sensitive indicator for evaluating cardiac function damage.

Distribution of enteroviruses in hospitalized children with hand, foot and mouth disease and relationship between pathogens and nervous system complications.

BACKGROUND: To explore the relationship between enteroviruses and hospitalized children with hand, foot and mouth disease (HFMD) complicated with nervous system disease. 234 hospitalized HFMD patients treated in Shengjing Hospital, Liaoning Province were analyzed retrospectively. Based on the presence and severity of nervous system disease, the patients were grouped as follows: general patients, severely ill patients, critically ill patients and fatal patients. Based on the detected pathogen, the patients were grouped as follows: Enterovirus 71 (EV71) infection, coxsackie A16 (CA16) infection and other enterovirus (OE) infection. RESULTS: Of the 423 hospitalized patients, most were admitted in July 2010(129/423, 30.5%). Enteroviruses were detected in 177(41.8%). 272/423 patients were male (64.3%), and fatal patients had the greatest proportion of male patients (p < 0.05). EV71 infection was found in 89/423 patients (21%). CA16 infection was detected in 8/423 patients (16.1%). Compared to group CA16, patients in group EV71 were hospitalized earlier, and the duration of hospitalization was longer (p < 0.05). Of the 92 patients with nervous system damage, 65 were infected with EV71 and 19 were infected with CA16. Among these CA16 infected patients, 2 had brainstem encephalitis and 1 had AFP. There were more patients with nervous system dysfunction in group EV71 than in groups CA16 or OE (p < 0.05). The 5 fatalities all occurred in group EV71 patients (p < 0.05). Infection with EV71 was most likely to cause neurogenic pulmonary edema (p < 0.05). Patients in group EV71 had a higher rate of suffering from coma and limb movement disorder than patients in groups CA16 or OE (p < 0.05). CONCLUSION: The disease progresses faster in EV71-infected HFMD patients. These patients are more likely to suffer nervous system damage, neurogenic pulmonary edema, severe sequelae or death. CA16 and other enteroviruses can also cause HFMD with severe nervous system complications.

[Treatment of congenital heart disease complicated by severe bronchopneumonia in infants].

OBJECTIVE: To study the treatment and the treatment outcome in infants with congenital heart disease complicated by severe pneumonia and heart failure. METHODS: The clinical data of 24 infants with congenital heart disease (left to right shunt) complicated by severe pneumonia and heart failure between January 2007 and December 2007 were retrospectively reviewed. RESULTS: Twenty-two infants recovered and 2 died. Severe pneumonia and heart failure were refractory even after 1-2 months medical treatment in 6 infants at ages of <6 months. They then underwent an open heart surgery under the mechanical ventilation and tracheal intubations and were successfully cured. The other 18 infants underwent a selective heart surgery after pneumonia and heart failure had been improved. Sixteen infants were successfully cured and 2 died of postoperative low cardiac output syndrome and diffuse intravascular clotting. CONCLUSIONS: The heart surgery should be performed early when the medical treatment does not work in infants with congenital heart disease complicated by severe pneumonia and heart failure. This may improve their outcome.

[Etiology of acute upper respiratory tract obstruction in infants: analysis of 12 cases].

OBJECTIVE: To study the etiology of acute upper respiratory tract obstruction in infants. METHODS: The medical data of 12 infants with acute upper respiratory tract obstruction were retrospectively reviewed. The patients received the examinations of laryngoscopy and CT scans for larynx and lungs. RESULTS: All of the 12 infants presented with laryngeal stridor. Eight infants (67%) were diagnosed as congenital simple laryngeal stridor before admission. Based on the clinical features, laboratory examinations, imaging examinations and laryngoscopy, 4 (33%) were definitely diagnosed with thyroglossal ductal cyst, 1(8%) with abscess-emphysema in the posterior wall of pharynx, 1(8%) with cervicallymphangioma, 2 (16%) with subglottic stenosis, and 4 (33%) with acute laryngitis. CONCLUSIONS: Acute upper respiratory tract obstruction is easily misdiagnosed in infants. Thyroglossal duct cyst is a common cause of upper respiratory tract obstruction/laryngeal stridor. It is recommend that laryngoscopy and CT scans for larynx should be performed in infants with laryngeal stridor.

[Relationship between alveolar epithelial type II cells and pulmonary surfactant protein A levels in young rats with acute lung injury].

OBJECTIVE: This study examined the relationship between the ultrastructural alterations of alveolar epithelial cells type II (AEC-II) and pulmonary surfactant protein A (SP-A) levels in the lung tissue of young rats with acute lung injury (ALI) in order to explore the possible mechanism of ALI. METHODS: Forty-eight young Sprague-Dawley rats were randomly divided into control and ALI groups. The rats in the ALI group were intraperitoneally injected with 4 mg/kg of lipopolysaccharide (LPS) in order to induce ALI. The control subjects were injected with the same volume of normal saline. Rats were sacrificed at 24, 48 and 72 hrs after LPS or NS injection. Lung samples were obtained from the lower parts of the left lung and fixed with 2.5% glutaraldehyde for transmission electron microscope examination and for Western blot test of SP-A. RESULTS: The microvilli of AEC-II disappeared 24 hrs after LPS injection. After 24 and 48 hrs of LPS injection, lamellar body (Lb) increased in number, enlarged in size and reduced in density, and the ring-like arrangement of Lb was present. By 48 hrs after LPS injection, giant Lb with vacuole-like deformity appeared. The contents of lung SP-A in the ALI group 24 hrs (6.52+/-0.62 vs 5.02+/-0.35; P<0.01) and 48 hrs (6.65+/-0.62 vs 5.01+/-0.36; P<0.01) after LPS injection were significantly higher than those in the control group. By 72 hrs after LPS injection, Lbs ruptured and were reduced in number. The shape of the nuclei was irregular and the border was blurred. The content of lung SP-A was greatly reduced in the ALI group 72 hrs after LPS injection compared with that in the control group (3.87+/-0.50 vs 5.22+/-0.36; P<0.01). CONCLUSIONS: The alterations of AEC-II and lung SP-A were time-dependent in young rats with ALI induced by LPS. In the early stage of ALI, the lung SP-A content showed a compensatory increase. With the increasing injury of AEC-II cells, the secretion of SP-A presented with a decompensation and the lung SP-A content decreased. This may be one possible mechanism for the development of ARD.

[Changes of pulmonary surfactant protein A in young rats with acute lung injury induced by lipopolysaccharide].

OBJECTIVE: Pulmonary surfactant protein A (SP-A) plays an important role in the maintenance of pulmonary surfactant function and innative immune defence. This study aimed to explore the changes of SP-A concentration in the lungs of young rats with acute lung injury. METHODS: Sprague-Dawley rats were randomly assigned to control and lung injury groups. Acute lung injury was induced by intraperitoneal injection of lipopolysaccharide (LPS) (4 mg/kg) in the lung injury group. The same amount of normal saline was given for the control group. The two groups were subdivided into 6 groups sacrificed at 6, 12, 24, 36, 48 and 72 hrs of injection (n=8 each). Western blot was employed to detect SP-A concentration in the lung tissues. RESULTS: SP-A concentration in the lung injury group was not different from the the control group within 12 hrs after LPS injection. SP-A concentration in the lung injury group was elevated significantly during 24-48 hrs after LPS injection, peaking at 36 hrs (6.94+/-0.80 vs 5.01+/-0.36; P< 0.01), compared with the controls. However, SP-A concentration in the lung injury group was significantly reduced 72 hrs after LPS injection compared with the controls (P< 0.01). CONCLUSIONS: The changes of lung SP-A concentration in rats following acute lung injury were time-dependent. The transient elevation of SP-A concentration in the lungs indicated a strong compensation ability of SP-A in the host defence against acute lung injury.

Effects of dexamethasone on the ultrastructure of alveolar type II cells in young rats with lipopolysaccharide-induced acute lung injury.

OBJECTIVE: Alveolar type II (AT II) cells play a crucial role in the maintenance of pulmonary surfactant homeostasis and pulmonary immunity. The effects of dexamethasone (Dex) on the ultrastructure of AT II cells after acute lung injury remain unknown. This study focused on the ultrastructural changes caused by acute lung injury and on the effects of Dex administration on these ultrastructural changes in young rats. METHODS: Seventy-two 21-day-old Sprague-Dawley rats were randomly divided into control, acute lung injury and Dex-treated groups. Rats in the lung injury group were intraperitoneally injected with 4 mg/kg lipopolysaccharide (LPS) in order to induce acute lung injury, while the control rats were injected with the same amount of normal saline (NS). The Dex-treated group was injected first with LPS followed 1 hr later by Dex (5 mg/kg) injection. Eight rats in each group were sacrificed 24, 48 and 72 hrs after LPS or NS injection. Lung samples were obtained from the lower parts of left lungs and fixed with 2.5% glutaraldehyde for transmission electron microscope examination. RESULTS: Microvilli of AT II cells disappeared and the number of lamellar bodies (LBs) increased in the lung injury group 24 hrs after LPS injection. The ring-like arrangement of LBs around nuclei was present until 48 hrs after LPS injection. By 48 hrs after LPS injection, giant LBs with vacuole-like abnormalities appeared. The shape of nuclei became irregular and the border of the nuclei became blurred. By 72 hrs after LPS injection, the number of LBs was obviously reduced; nucleoli disappeared; and karyolysis occurred in some of the nuclei. In contrast, in the Dex-treated group, LBs crowded on one side of AT II cells and exocytosis appeared on the same side by 24 hrs after LPS injection. By 48 hrs, the number of LBs was reduced. The number of mitochondria increased, and some of them became swollen and enlarged. However, by 72 hrs, the number of LBs increased and the ring-like arrangement of LBs around the nucleus again appeared. CONCLUSIONS: Ultrastructural changes of AT II cells following lung injury induced by LPS were time-dependent in young rats. Dex may ameliorate AT II cell injury and promote functional restoration of AT II cells in LPS-induced acute lung injury.

[Effect of losartan on lung fibrosis in neonatal rats with hyperoxia-induced chronic lung disease].

OBJECTIVE: In addition to regulating blood pressure, angiotensin II is involved in lung fibrogenesis. This study aimed to explore the effect of losartan, an angiotensin II type 1 receptor antagonist, on lung fibrosis in neonatal rats with hyperoxia-induced chronic lung disease (CLD) and its possible mechanisms. METHODS: Neonatal Wistar rats were randomly divided into four groups within 24 hrs after birth: room air exposure, hyperoxia exposure (85%-90% O2), hyperoxia exposure + losartan, and hyperoxia exposure + placebo. Losartan (5 mg/kg/d) or placebo was administered beginning on the 6th day after birth. After 7, 14 and 21 days of exposure, 8 rats in each group were sacrificed. Lung histological changes were evaluated by hematoxylin-eosin staining. Levels of hydroxyproline (HYP), superoxide dismutase (SOD) and malondialdehyde (MDA) in lung tissues were determined by spectroscopy. RESULTS: Hyperoxia exposure resulted in decreased alveolar septation, enlarged terminal air space, increased collagen deposition, pulmonary hemorrhage, and pulmonary consolidation. In the hyperoxia exposure + losartan group, the alveolar septum became thinner and lung fibrosis was alleviated, but the alveolar space was not obviously deflated and the number of secondary septum was not increased. Hyperoxia exposure increased significantly the HYP contents in lung tissues 14 and 21 days after exposure. Addition of losartan to the hyperoxia exposure resulted in decreased HYP contents (471.46 +/- 30.63 mu g/kg vs 545.15 +/- 34.90 mu g/kg for hypoxia alone; P < 0.01) after 21 days of exposure. SOD activity increased 7 days after hyperoxia exposure and then decreased to levels similar to the air exposure group. MDA levels increased to a peak at 7 days and remained at higher levels through 21 days of exposure when compared with the air exposure group (P < 0.01). Losartan treatment significantly increased SOD activities (82.94 +/- 4.62 U/mg protein vs 67.78 +/-8.02 U/mg protein; P < 0.01) and decreased MDA levels (30.54 +/- 5.89 nmol/mg protein vs 48.75 +/- 8.09 nmol/mg protein, P < 0.01) compared with the hyperoxia exposure group 21 days after exposure. CONCLUSIONS: Losartan attenuated lung fibrosis in neonatal rats with hyperoxia-induced CLD, possibly through an increase of antioxidase enzyme activity and reduction of lipid peroxidation.

[Protection of captopril against chronic lung disease induced by hyperoxia in neonatal rats].

OBJECTIVE: This study examined the protein and mRNA contents of angiotesin converting enzyme (ACE), angiotensin II (Ang II) and type I collagen and the changes of lung histomorphology in neonatal rats with hyperoxia-induced chronic lung disease (CLD) and investigated the protection of captopril against CLD and the possible mechanism. METHODS: A total of 240 term neonatal Wistar rats were randomly assigned into air, model, normal saline and captopril-treated groups (n=60 each). The air group was exposed to room air (FiO2=0.21) immediately after birth. The other three groups were exposed to hyperoxia (FiO2=0.9) for 21 days to induce lung injury. The captopril-treated group received captopril daily (30 mg/kg) by intragastric administration between the 7th and 21st days of hyperoxia exposure. The normal saline group was administrated with normal saline instead. At each time interval of 1, 3, 7, 14 and 21 days after experiment, six rats of each group were randomly chosen and sacrificed. The protein and mRNA levels of ACE, Ang II and type I collagen were measured by enzyme-linked immunosorbentassay, radio-immunity technique and RT-PCR. The changes of lung histomorphology were observed under a light microscope. RESULTS: The protein and mRNA expressions of ACE, Ang II and type I collagen increased significantly in the model and normal saline groups on the 14th and peaked on the 21st days of exposure compared with those of the air group (P < 0.05 or 0.01). Captopril treatment reduced significantly the protein and mRNA expressions of ACE, Ang II and type I collagen compared the model and normal saline groups on the 14th and 21st days, although the values were significantly higher than the air group (P < 0.05 ). The histopathologic examination demonstrated broadened lung interstitium and reduced alveolar quantity and lung fibrosis was developed in the model and normal saline groups on the 14th day of exposure. Captopril treatment obviously alleviated the changes of lung histomorphology. CONCLUSIONS: Captopril can inhibit the protein and mRNA expressions of ACE, Ang II and type I collagen and alleviate lung fibrosis in neonatal rats with hyperoxia-induced lung injury/CLD. This may contribute to one of the possible mechanisms underlying the protective effects of captopril against lung injury/CLD.

[Protective effects of captopril on hyperoxia-induced lung injury in neonatal rats].

OBJECTIVE: To study the effect of captopril on the histopathology and bronchoalveolar lavage fluid (BALF) in neonatal rats exposed to hyperoxia. METHODS: Forty term neonatal Wistar rats were randomly assigned into Air control, Model, Normal saline control and Captopril-treated groups (n=10 each). The Air control group was exposed to air (FiO2=0.21). The remaining three groups were continuously exposed to hyperoxia (FiO2=0.90) . During exposure the Captopril-treated group received intragastric captopril (60 mg/kg daily) and the Normal saline control group was administered with normal saline. The Model group had no treatment. At the 14th and 21st days of exposure, the subjects were sacrificed. The lung coefficient and the protein contents and inflammatory cells in BALF were determined. The changes of lung histomorphology were observed. RESULTS: The lung coefficient and the protein contents, the total number of cells and the percentage of neutrophils, lymphocytes and eosinophils in BAFL increased significantly in the Model and Normal saline control groups on the 14th and 21st days of exposure compared with those of the Air control group. Captopril treatment significantly reduced the lung coefficient and the protein contents, the total number of cells and the percentage of neutrophils and eosinophils in BALF. On the 14th day the lung coefficient decreased from 9.72 +/- 0.67 mg/g to 8.63 +/- 0.35 mg/g (P < 0.05); the protein contents in BALF from 0.619 +/- 0.023 g/L to 0.486 +/- 0.027 g/L (P < 0.05); and the total number of cells in BALF from (80.57 +/- 9.28)x10(4)/mL to (48.62 +/- 1.53)x10(4)/mL (P < 0.01) compared with the Model group. On the 21st day the lung coefficient decreased from 10.67 +/- 0.87 mg/g to 8.76 +/- 0.89 mg/g (P < 0.05); the protein contents in BALF from 0.978 +/- 0.012 g/L to 0.759 +/- 0.042 g/L (P < 0.05); and the total number of cells in BALF from (92.86 +/- 10.32) x10(4)/mL to (35.52 +/- 3.89) x10(4)/mL (P < 0.05) compared with the Model group. There were however significant differences in these results between the Captopril-treated and Air control groups. The histopathological examination demonstrated different degrees of alveolitis, broaden interstitium and reduced alveolar quantity in the Model and Normal saline control groups. The pathological changes were markedly alleviated after captopril treatment. CONCLUSION: Captopril may have protective effects on lung injury induced by hyperoxia.