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.

Conclusion: Intravenous administration of Ala-Gln can effectively protect the lung from sepsis induced injury.