Protective effects of alanyl-glutamine on acute lung injury induced by lipopolysaccharide in rats.
OBJECTIVE
To investigate the effect of alanyl-glutamine (Ala-Gln) on acute lung injury (ALI) in rats induced by sepsis and its mechanisms.


METHODS
Forty healthy adult Wistar rats were randomly divided into a control group, a lipopolysaccharide (LPS)-induced shock group, an Ala-Gln treated group, and a glutamine (Gln) treated group. The control group received an intravenous infusion of 28 mL/kg lactated Ringeros solution(LR). The LPS-induced shock group received an intravenous administration of 25 mL/kg LR, and then 3 mL/kg (6 mg/kg) LPS (L-2880, Sigma, America). The Ala-Gln treated group received 4.5% Dipeptiven (25 mL/kg, equaling 0.75 g/kg Gln) immediately before 3 mL/kg (6 mg/kg) LPS.The Gln treated group received 3% glutamine ( 25 mL/kg, 0.75 g/kg) immediately before 3 mL/kg (6 mg/kg) LPS. Serum (1 mL) was drawn via the femoral vein or cardiac puncture before LPS injection (T(0)) and 6 h after the administration of LPS (T(1)), respectively. All rats were killed 6 h after LPS infusion. The samples of pulmonary tissue and lung lavage fluid were collected after experiments. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-8 (IL-8) in the serum at T(0) and T(1) were detected by ELISA. Apoptosis in the lung epithelial cells was detected with TUNEL assays. The lung wet/dry(W/D)weight ratio and total protein in the bronchoalveolar lavage fluid (BALF) were measured.


RESULTS
Six hours after the infusion of LPS (T(1)), the plasma concentrations of TNF-alpha, IL-1beta, and IL-8 were much lower in the Ala-Gln treated group and the Gln treated group than those in the LPS-induced shock group (P<0.05). Compared with the LPS-induced shock group, Ala-Gln and Gln significantly reduced the increase in the lung wet/dry weight ratio (P<0.05) and attenuated the morphological lung damage.


CONCLUSIONS
Intravenous administration of Ala-Gln can effectively protect the lung from sepsis induced injury.
Liu
Jing-Chen
JC
Department of Anesthesiology, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China. liujcnn@163.com
Wang
Hai-Tang
HT
Wang
Wei
W
D000818:Animals; D004151:Dipeptides / Q000494:pharmacology / Q000627:therapeutic use*; D008070:Lipopolysaccharides; D055370:Lung Injury / Q000188:drug therapy* / Q000209:etiology; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000139:chemically induced* / Q000150:complications
D004151:Dipeptides; D008070:Lipopolysaccharides; D020011:Protective Agents; C054122:alanylglutamine