OBJECTIVETo explore the association of epithelial sodium channel alpha subunit (alphaENaC) with terbutaline-induced transient enhancement of pulmonary edema clearance in adult rats with acute lung injury (ALI).

METHODSThe effect of 1-h intratracheal terbutaline treatment on pulmonary edema clearance in adult rats with experimental ALI was observed by blood gas analysis, lung tissue HE staining, and extravascular lung water (EVLW) content measurement. The mRNA and protein expressions of alphaENaC in the lung tissues were detected by fluorescence quantitative real-time RT-PCR and Western blotting, respectively.

RESULTTerbutaline treatment of the rats with ALI resulted in significant differences in PaO2, oxygenation index, and EVLW from those in ALI group without treatment. No significant differences in pulmonary alphaENaC mRNA and protein expressions were noted between the normal control, ALI, and terbutaline-treated ALI groups.

CONCLUSIONSIntratracheal terbutaline administration for 1 h can significantly promote pulmonary edema clearance in adult rats with ALI, and this effect is not mediated by alphaENaC gene expression.

Acute Lung Injury ; chemically induced ; complications ; drug therapy ; genetics ; metabolism ; Animals ; Epithelial Sodium Channels ; genetics ; metabolism ; Female ; Male ; Oleic Acid ; Pulmonary Edema ; drug therapy ; etiology ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Terbutaline ; therapeutic use

PURPOSE: Granulocyte colony stimulating factor (G-CSF) has been known to increase neutrophil production and have anti-inflammatory properties, but the effect of G-CSF on pulmonary system is in controversy. We investigated whether G-CSF treatment could attenuate hyperoxia-induced lung injury, and whether this protective effect is mediated by the down-modulation of inflammatory responses in a neonatal rat model. MATERIALS AND METHODS: Newborn Sprague-Dawley rats (Orient Co., Seoul, Korea) were subjected to 14 days of hyperoxia (90% oxygen) beginning within 10 h after birth. G-CSF (20 microg/kg) was administered intraperitoneally on the fourth, fifth, and sixth postnatal days. RESULTS: This treatment significantly improved hyperoxia-induced reduction in body weight gain and lung pathology such as increased mean linear intercept, mean alveolar volume, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling positive cells. Hyperoxia-induced activation of nicotinamide adenine dinucleotide phosphate oxidase, which is responsible for superoxide anion production, as evidenced by upregulation and membrane translocation of p67phox was significantly attenuated after G-CSF treatment, as were inflammatory responses such as increased myeloperoxidase activity and mRNA expression of transforming growth factor-beta. However, the attenuation of other proinflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 was not significant. CONCLUSION: In sum, G-CSF treatment significantly attenuated hyperoxia-induced lung injury by down-modulating the inflammatory responses in neonatal rats.
Animals ; Animals, Newborn ; Blotting, Western ; Female ; Granulocyte Colony-Stimulating Factor/*therapeutic use ; Hyperoxia/*complications ; In Situ Nick-End Labeling ; Interleukin-6/genetics ; Lung/*drug effects/*metabolism ; Lung Injury/*drug therapy/etiology/genetics/metabolism ; NADPH Oxidase/metabolism ; Peroxidase/metabolism ; Pregnancy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Transforming Growth Factor beta/genetics ; Tumor Necrosis Factor-alpha/genetics ; Weight Gain/drug effects

OBJECTIVE: To investigate the effect of hemin on lung injury following severe acute pancreatitis (SAP) in rats and to explore its rudimentary mechanism. METHODS: Thirty-six rats were randomly divided into 3 groups: a control group, a SAP model group, and a hemin-pretreated group. Rats were sacrificed 12 hours after inducing SAP model. The pathological changes of the pancreas and lungs were observed under light microscope. Expression of heme oxygenase (HO-1) mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR), NF-kappaB activity in the lung tissues was detected by enzyme linked immunosorbent assay (ELISA), and the serum levels of TNF-alpha and IL-6 were measured by ELISA. RESULTS: HO-1 was induced during experimental SAP, NF-kappaB activity in the lung tissues was elevated after the induction of SAP and the serum levels of TNF-alpha and IL-6 were significantly elevated. Hemin further upregulated the expression of HO-1 mRNA, decreased NF-kappaB activity drastically, and inhibited the serum levels of TNF-alpha and IL-6 significantly (P < 0.05). Hemin could treat SAP by alleviating the pancreatic and lung injury. CONCLUSION Hemin moderates the inflammatory reaction and decreases the lung injury following SAP, the mechanism of which may be closely related to the upregulation of expression of HO-1 mRNA, the inhibitory effect on NF-kappaB, and adjustment of cytokines.
Acute Lung Injury ; drug therapy ; etiology ; Animals ; Cytokines ; genetics ; metabolism ; Female ; Heme Oxygenase (Decyclizing) ; genetics ; metabolism ; Hemin ; therapeutic use ; Male ; NF-kappa B ; genetics ; metabolism ; Pancreatitis, Acute Necrotizing ; complications ; drug therapy ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction