[Effects and mechanisms of endotoxin pretreatment on lung of rat in endotoxemia].
OBJECTIVE
To observe the effects and mechanisms of endotoxin pretreatment on the rat lung in endotoxemia.


METHODS
Eighty-four male Wistar rats were divided into seven groups (each group containing 12 rats): saline control and lipopolysaccharide (LPS)-treated 2 h, 4 h, 6 h groups and LPS-pretreated 2 h, 4 h, 6 h groups. LPS-pretreated rats were administrated with intraperitoneal injection of 0.25 mg/kg LPS. After 24 hours, they were injected with 0.5 mg/kg of LPS. Saline control and LPS-treated rats received an equivalent amount of saline. After 72 hours, LPS-treated and LPS-pretreated rats were intravenously injected with 10 mg/kg of LPS. An equivalent amount of saline was injected in the control rats. Blood was drawn from the carotid artery in LPS-treated and LPS-pretreated rats and sacrificed after intravenous injection of LPS 2, 4, 6 hours. Following saline injection of control rats, blood was drawn from the carotid artery after 6 hours. Arterial blood was drawn for blood gas analysis. The lungs were removed for detecting the mRNA levels of intercellular adhesion molecule-1 (ICAM-1) by reverse transcription polymerase chain reaction and the protein levels of inhibitor kappa B-alpha (I kappa B-alpha) by immunohistochemical staining. Bronchoalveolar lavage was performed in the right lung. Cell counts were evaluated with a light microscopy. The supernatant of bronchoalveolar lavage fluid (BALF) was assayed for the level of protein. The whole lung was weighed and the value was used to determine the lung-body index. The tissue was homogenized and centrifuged for the determination of myeloperoxidase enzyme (MPO) activity.


RESULTS
The rats exposed to LPS alone demonstrated an increase in lung-body index, protein in BALF, and MPO activity in the lung tissue. In contrast, the rats exposed to LPS pretreatment exhibited a significant decrease in lung-body index, protein in BALF, and MPO activity. There was a significant decrease in the level of arterial bicarbonate in the LPS-treated rats in comparison with saline-treated and LPS-pretreated animals at 2 hours to 6 hours after LPS administration. The decrease of arterial bicarbonate was compensated by alveolar hyperventilation in LPS-treated animals, with a significant decrease in partial pressure of carbon dioxide. At the same time, partial pressure of oxygen decreased significantly compared with saline control animals and LPS-pretreated animals. LPS-treated rats showed a significant gradually increase in ICAM-1mRNA in the lung in comparison with the saline group. In contrast, ICAM-1mRNA levels in rats pretreated with LPS was lower than that in LPS-treated rats. In LPS-treated animals, LPS caused a decrease of I kappa B-alpha protein expression at 2 hours, returned to control level at 4 hours, and remained at 6 hours. There was no decrease of I kappa B-alpha protein expression in LPS-pretreated animals.


CONCLUSIONS
The results in this study showed that administration of a small dose of LPS 72 hours before endotoxemia caused a attenuation effect on lung injury, which may be correlated to I kappa B-alpha expression induced by LPS pretreatment.
Liu
Gui-ming
GM
Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang 110001, China.
Ding
Xue-qin
XQ
Xu
Guo-zhong
GZ
Wang
Jun-ke
JK
D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D019446:Endotoxemia / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D010100:Oxygen / Q000097:blood; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D002245:Carbon Dioxide; D009195:Peroxidase; D010100:Oxygen