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To study the expression of extracellular signal regulated protein kinase (ERK) 1/2 in lung tissues of newborn rats with chronic lung disease (CLD) caused by hyperoxia.Forty-eight full-term newborn rats were randomly divided into two groups: hyperoxia and control. The two groups were exposed to a hyperoxic gas mixture (0.90 O(2)) for an induction of CLD and room air within 12 hrs after birth, respectively. The levels of ERK1/2 protein and mRNA in lung tissues were measured using immunohistochemistry, Western blot and real-time PCR methods on postnatal days 3, 7 and 14. The severity of pulmonary fibrosis was evaluated.The expression of p-ERK protein in lung tissues in the hyperoxia group was significantly higher than that in the control group on postnatal days 7 and 14 (P0.01). There were no significant differences in the levels of total ERK1/2 protein and ERK1/2 mRNA.The activation of phosphorated ERK1/2 may lead to lung fibrosis caused by hyperoxia in newborn rats.

To study the effects of transforming growth factor-β1 (TGF-β1) on the gene expression of connective tissue growth factor (CTGF) in cultured lung fibroblasts of embryonic rats in vitro.Wistar rats of embryonic 19 days were used for primary culture of lung fibroblasts (LFs). The cells in the experimental group were treated by different concentrations (1, 5 or 10 ng/mL) and different durations (12, 24 or 48 hrs) of TGF-β1 to stimulate the LFs. The cells in the control group were cultured in serum-free medium. RT-PCR method was applied to detect CTGF mRNA expression in LFs.Compared with the control group, the levels of CTGF mRNA in LFs in the experimental group increased significantly (P0.05). CTGF mRNA expression gradually increased with increasing concentration and duration of TGF-β1 treatment (P0.05).TGF-β1 can stimulate CTGF gene expression in LFs and increase CTGF gene expression in a dose-and time-dependent manner.

This study investigated the expression of platelet-derived growth factor-B (PDGF-B) and its receptor-β (PDGFR-β) in rat cerebral cortex following sepsis and explored the possible underlying mechanism of neuro-protective effect of glutamine (Gln).One hundred and twenty 10-day-old Wistar rats were randomly divided into three groups: a control group that received an intraperitoneal injection of normal saline (1 mL/kg), a sepsis group that received an intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg), and a Gln treatment group that was administered with Gln (1.346 g/kg) 1 hr before LPS injection. The rats were subdivided into 5 groups sacrificed at 2, 6, 12, 24 and 72 hrs after LPS or normal saline injection (n=8). The distribution and expression of PDGF-B and PDGFR-β in the cerebral cortex were ascertained by immunohistochemistry and Western blot.The immunohistochemistry results showed that the PDGF-B and PDGFR-β expression in the cerebral cortex increased significantly in the Gln treatment group 72 hrs after LPS injection compared with that in the control and the sepsis groups. The Western blot results showed that the PDGF-B expression in the brain tissue in the sepsis and the Gln treatment groups were significantly lower than that in the control group 2, 6, and 12 hrs after LPS injection, while the Gln treatment group had increased PDGF-B expression compared with the sepsis group 12 and 72 hrs after LPS injection. Compared with the control group, the PDGFR-β expression in the brain tissue in the sepsis group increased 2 and 6 hrs after LPS injection but decreased significantly 72 hrs after LPS injection. There were no significant differences in the PDGFR-β expression between the Gln treatment and the control groups at all different time points.Gln can increase the PDGF-B and PDGFR-β expression in the brain tissue of rats with sepsis. The increased PDGF-B and PDGFR-β expression might contribute to neuro-protective effects of Gln.

To study the effect of melatonin, a potent antioxidant both in vitro and in vivo, on hyperoxia-induced oxidant/antioxidant imbalance in the lung of neonatal rats with chronic lung disease (CLD).Ninety neonatal rats were randomly divided into three groups (n=30 each): air-exposed, hyperoxia-exposed, melatonin-treated (4 mg/kg melatonin was administered 30 minutes before hyperoxia exposure and once daily after exposure). CLD was induced by hyperoxia exposure (FiO2=0.85). Lung specimens were obtained 3, 7, and 14 days after exposure (n=10 each) for histopathologic examination. The levels of total antioxydase capacity (T-AOC), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), myeloperoxidase (MPO), catalase (CAT), nitrite/nitrate, and malondialdehyde (MDA) in the lung were assayed by the spectrophotometer.The histopathologic examination showed that lung damage was obviously alleviated in the melatonin-treated group. The levels of T-AOC, GSH-Px, SOD and CAT in the lung were significantly higher in the melatonin-treated group than those in the other two groups at all time points (p0.05). The levels of MPO, nitrite/nitrate and MDA in the lung increased significantly in the untreated hypoxia-exposed group compared with those in the air-exposed group at all time points (p0.05 or 0.01), while the levels of MPO, nitrite/nitrate and MDA in the melatonin-treated group were significantly reduced as compared with the untreated hypoxia-exposed group (p0.05).Melatonin may reverse oxidant/antioxidant imbalance in hyperoxia-induced lung disease, thus providing a protective effect against CLD in neonatal rats.

The present study aimed to characterize the clinical presentations and magnetic resonance imaging including conventional MRI and diffusion-weighted imaging (DWI) in newborns with cerebral infarction.Clinical records of 16 newborn infants with cerebral infarction were reviewed. All cases underwent DWI examination in addition to conventional MRI examination [T1-weighted (T1W) and T2-weighted (T2W)]within 5 days after birth. Five patients received the second MRI examination at the age of 11 to 18 days.Eight patients had antenatal risk factors, 9 had intranatal risk factors, and no postnatal risk factors were found. Seizures as the first symptom were noted in 11 neonates, with a short duration and a low frequency. The first imaging examination (within 5 days) showed a slight hypointensity on T1W, a slight hyperintensity on T2W and significantly increased signal intensity with a clear boundary on DWI in the lesions. In the MRI re-examination, more obvious hypointensity on T1W and hyperintensity on T2W were noted, while hypointensity was shown on DWI in the lesions compared with the first imaging results.Seizures characterized by short duration and low frequency usually may be the first symptom in newborns with cerebral infarction. A hyperintensity on DWI was shown in the lesions at the early stage of neonatal cerebral infarction. A hypointensity on T1W and a hyperintensity on T2W were demonstrated in the lesions with increasing disease duration.

Alveolar epithelium impairment is one of pathological changes associated with chronic lung disease (CLD). Hoxb5 is one of the few homeobox genes strongly expressed in the developing lung. This study investigated the expression of HoxB5, SPC and AQP5 in rats with CLD in order to explore the role of Hoxb-5 in impairment and reparation of alveolar epithelium.Eighty neonatal rats were randomly exposed to hyperoxia (model group) or to room air (control group) (n=40 each). The CLD model was induced by hyperoxia exposure. The expression of HoxB5, SPC and AQP5 protein and mRNA in the lung tissue was detected by immunohistochemistry and RT-PCR 1, 3, 7, 14 and 21 days after exposure.In the model group HoxB5 expression significantly decreased 7, 14 and 21 days after hyperoxia exposure. SPC expression decreased 3 days after hyperoxia exposure but increased significantly 7, 14 and 21 days after hyperoxia exposure as compared to the control group. AQP5 expression was progressively reduced with prolonged hyperoxia exposure.Hyperoxia exposure may lead to alveolar epithelial cell (AEC) damage in neonatal rats. The increased SPC expression and decreased AQP5 expression suggested that the ability of differentiation and transformation of AECII into AECI decreased in neonatal rats with CLD. The decreased HoxB5 expression following hyperoxia exposure might contribute to a decreased ability of differentiation of AECII.

To study the relationship between clinical and imaging features in neonates with hypoglycemic brain injury.Sixteen neonates with hypoglycemic brain injury received a MRI scan with the sequences of T1WI, T2WI and DWI within 48 hrs after admission. Of the 16 patients, 11 received second MRI scan at two weeks of their lives, and 3 received a third scan at ages of 1-5 months.Repeated seizures, lethargy and hypotonia were common clinical manifestations. Five severe hypoglycemia cases presented coma, respiratory failure and even cardiorespiratory arrest. The minimum mean value of whole blood glucose (WBG) in the 16 patients was 0.98+/-0.43 mmol/L, and that of the 5 severe cases was 0.72+/-0.42 mmol/L. EEG showed intermittent low voltage in the mild hypoglycemia cases. Flatten pattern and even electrocerebral silence was noted in the severe cases. Occipital and parietal cortexes (OPC) injuries were found in all of the 16 patients and 2 patients had concurrent periventricular white matter injury. A widespread involvement of cortex was found in the 5 severe hypoglycemia cases in which 1 showed widespread involvement of white matter, and 2 showed involvement of basal ganglia and thalamus. The 5 patients with widespread cortex injury and the 2 patients with OPC and periventricular white matter injury showed lower minimum WBG levels compared with those with OPC alone (0.71+/-0.35 mmol/L vs 1.19+/-0.42 mmol/L; t= 2.4124, P0.05). The appearance of high-intensity signals on DWI was shown as early changes of signals in all of the 16 patients. The second MRI scan for 7 patients with OPC showed abnormal signals on T1WI and T2WI in 5 patients and abnormal signals on DWI in 3 cases. Cerebral atrophy and multicystic encephalomalacia were found in four patients with widespread involvement of cortex on DWI. In the follow-up one patient with OPC presented delayed myelination and one with concurrent white matter injury showed spastic diplegia. One patient with widespread involvement of cortex showed diffused encephalomalacia.The severity of hypoglycemic brain injury demonstrated by serial MRIs relates to the severity of hypoglycemia. The occipital and parietal areas are the most vulnerable following hypoglycemia in neonates. Severe hypoglycemic brain injury manifests as a widespread involvement of cortex, or combined with white matter, or basal ganglia and thalamus. DWI can show early hypoglycemic brain injury.

What is the best suitable position for neonates who were weaned from mechanical ventilation has not been identified. This study aimed to evaluate the effect of the supine and prone positions on oxygenation in neonates within 6 hrs after weaning from mechanical ventilation.Sixty neonates who were weaned from mechanical ventilation were randomly given prone or supine position (n=30 each). They all received oxygen inspiration and SPO2 was maintained in a normal range by adjusting the oxygen flow rate (FiO2). Blood PaO2 and PaCO2 levels were measured 1 and 6 hrs after weaning and then the alveolodouble ended arrowarterial oxygen partial pressure difference (A-aDO2), respiratory index and oxygenation index were calculated.Mean FiO2 used in the prone position group was significantly lower than that in the supine position group 1 and 6 hrs after weaning (P0.01). The value of A-aDO2 in the prone position group 1 hr (171.06+/-86.55 vs 253.62+/-71.56; P0.01) and 6 hrs after weaning (105.85+/-78.18 vs 208.48+/-86.80; P0.01) were significantly lower than that in the supine position group. The respiratory index in the prone position group 1 and 6 hrs after weaning (2.16+/-1.24 and 1.35+/-1.11) was also reduced compared to 3.74+/-1.68 and 3.65+/-1.28 in the supine position group (P0.01). In contrast, PaO2 in the prone position group 1 hr (88.70+/-32.65 vs 73.43+/-17.68; P0.01) and 6 hrs (84.10+/-13.95 vs 70.20+/-20.27; P0.01) after weaning was significantly higher than that in the supine position group. The oxygenation index in the prone position group 1 and 6 hrs after weaning (213.49+/-88.96 and 275.23+/-108.83) increased significantly compared to 141.54+/-43.25 and 160.62+/-63.03 in the supine position (P0.01).The prone position is better than the supine position for the improvement of oxygenation within 6 hrs after weaning from mechanical ventilation in neonates.

To investigate the role of connective tissue growth factor (CTGF) in pulmonary fibrosis in rats with hyperoxia-induced chronic lung disease (CLD).Eighty premature rats were randomly exposed to hyperxia (FiO2=0.90) or room air (control group) (n=40 each). CLD was induced by hyperoxia exposure. The expression of CTGF mRNA and transforming growth factor-beta 1 (TGF-beta 1), the levels of type I collagen and the proliferating cell nuclear antigen (PCNA) index were assayed with enzyme linked immunoadsorbent (ELISA), immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) on days 1, 3, 7, 14 and 21 after exposure.There were no differences in the levels of type I collagen, PCNA index, TGF-beta 1 protein and CTGF mRNA between the CLD and the control groups within 3 days after exposure. In the CLD group, the expression of TGF-beta 1 protein increased on the 7th day, remained at a higher level on the 14th and 21st day after exposure; the higher levels of type I collagen, PCNA index and CTGF mRNA were detected on the 14th day and peaked on the 21st day after exposure when comparing the control group. CTGF mRNA expression was positively correlated with type I collagen levels in the CLD group (gamma=0.89, P0.01).The expression of CTGF in lung tissues is associated with pulmonary fibrosis in CLD rats.

Extracellular matrix (ECM) deposition is a major reason of pulmonary fibrosis in hyperoxia-induced lung injury. However, the relevant mechanism has not been identified. This study examined the gene expressions of matrix metalloproteinases-8 (MMP-8, a catabolic enzyme of type I collagen) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in neonatal rats with hyperoxia-induced pulmonary injury in order to explore the role of MMP-8 and TIMP-1 in pulmonary fibrosis.Eighty term newborn rats were randomly exposed to hyperoxia (FiO2=0.90, hyperoxia group)and to room air (FiO2=0.21, control group)(n=40 each). Lung injury was induced by hyperoxia exposure. The content of type I collagen and the expressions of type I collagen protein and MMP-1 mRNA and TIMP-1 mRNA were assayed with enzyme linked immunoadsorbent (ELISA), immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) respectively on days 1, 3, 7, 14 and 21 after exposure.The content of type I collagen and the expression of type I collagen protein in the hyperoxia group were statistically higher than those in the control group at 14 and 21 days post-exposure. The MMP-8 mRNA expression decreased while the TIMP-1 mRNA expression increased significantly in the hyperoxia group as compared to the control group at 14 and 21 days post-exposure.Hyperoxia exposure down-regulates MMP-8 mRNA expression and up-regulates TIMP-1 mRNA expression. This results in a reduction of ECM degradation, thereby ECM deposition occurs in lung tissue, which may be an important mechanism of pulmonary fibrosis following hyperoxia-induced lung injury.

Lung fibrosis is the ultimate outcome of hyperoxia-induced chronic lung diseases (CLD) and connective tissue growth factor (CTGF) is correlated with fibrosis. This study investigated the role of CTGF in hyperoxia-induced CLD.Fifty premature rats were randomly exposed to hyperoxia (Model group) and to room air (Control group) (n = 25 each). CLD was induced by hyperoxia exposure. The expression of CTGF was detected by immunohistochemical method at 1, 3, 7, 14 and 21 days after exposure. The severity of pulmonary fibrosis was evaluated.In the Control group there was a slight expression of CTGF in the bronchial epithelial cells and vascular endothelial cells. The intensity and range of CTGF expression in the Model group were similar to the Control group on days 1, 3 and 7 of exposure. On the 14th day, CTGF was expressed in some alveolar epithelial cells, fibroblasts and interstitial cells, and the intensity of CTGF expression increased significantly compared with the Control group, with the IODT of CTGF of 10.53 +/- 4.24 vs 5.58 +/- 1.18 (P0.01). On day 21, the expression intensity and range of CTGF in the Model group (IODT: 16.61 +/- 5.39) increased compared with that of Control group (P0.01). The expression of CTGF was correlated with the degree of fibrosis in the Model group on days 14 and 21 (r = 0.903, r = 0.926 respectively, P0.01).The CTGF expression increased with the time of hyperoxia exposure and the development of fibrosis. CTGF is closely related to the development of hyperoxia-induced pulmonary fibrosis.