Protecting Effects Of Antioxidant Alpha Lipoic Acid On Experiment ALI/ARDS In Rat Model

ARDS is a disease process that is characterized by diffuse inflammation in the lung parenchyma. Though the respiratory supporting tecnique have developed , the mortality rates on ALI/ARDS patients remain more than 40%. It is now focus on to find new medcine to inhibite excess inflammation in lung tissue.Oxidant mediated tissue injury is likely to be important in the pathogenesis of ARDS. There was no difference in mortality among administrated groups by placebo, NAC and OTZ. However, the number of days of acute lung injury was decreased and there was also a significant improvement in biology parameters,such as cardiac index and PaO2,in antioxidant treatment. ɑ-lipoic acid is a naturally-occurring co-factor found in a number of multi-enzyme complexes regulating metabolism.Now it is not documented LA was administrated in ALI/ARDS.Objection:The objective of this experiment is to elucidate effects of ɑ-lipoic acid on endotoxin-induced acute lung injury in rats and to provide new medcine treatment of clinical implement in ARDS.Methods:Endotoxin-induced ALI/ARDS in SD rat model Induction of experimental ALI/ARDS was induced in SD male rat (200-250g) by injection of LPS(6mg/kg) from Escherichia coli 0111:B4. The pathophysiology changes on endotoxin-induced acute lung injury in rat after administrated by ɑ-lipoic acid. To evaluated effects of various dose of ɑ-lipoic acid and GSH on endotoxin-induced acute lung injury in rats,we measured PaO2,cell counting and protein in the bronchoalveolar lavage fluid, pulmonary wet/dry weight ratio, and lipid peroxidation in serum, TNF-α in serum and BALF, the survival time of rates and pathological features,including ultrastructure.Result 1. In the LPS group compared with the saline control group, PaO2 were significantly (P<0.01) decreased all gradually from 1h(75.69±11.01 mmHg)to 6h(57.97±15.74 mmHg)after administration of LPS. The lipid peroxidation were significantly (P<0.01) elevated all gradually from 1h(218.6±24.31 U.CARR) to 6h(367.4±46.41 U.CARR).The lung W/D ratio were significantly (P<0.01) increased all gradually from 1h(4.48±0.09) to 6h(4.82±0.09). Albumin concentration in BAL Fluids were significantly (P>0.01) elevated all gradually from 1h(0.324±0.05) to 6h(0.835±0.1). Total Cell Counts in BAL Fluids were significantly (P<0.01) elevated all gradually from 1h(4.4±0.77×107/L) to 6h(9.35±1.48×107/L). The level of TNF-ɑ in serum were significantly (P<0.05) increased all from 1h(1.018±0.38 ng/ml) to 6h(0.096±0.021ng/ml).The peak is in 1h(1.018±0.38 ng/ml). The level of TNF-ɑ in BALF were increased all from 1h(0.259±0.04 ng/ml) to 6h(0.429±0.05ng/ml). This change was significant (P<0.01) in 1h and 6h. Histologically,there were thickening of alveolar walls with increasing leukocyte (PMN and monocyte) infiltration accompanied by significant red cell congestion. LPS infusion was also associated with obvious signs of tissue edema, enlarged connective tissue septa,and partly collapsed pulmonary alveolus.2. In the LA(100mg/kg) group compared with the LPS group, PaO2 were significantly (P>0.01) increased all from 1h(92.96±9.56mmHg)to 6h(87.38±3.93mmHg). The lipid peroxidation were significantly (P>0.01) decreased all from 1h(126.6±28.74 U.CARR) to 6h(187.2±24.35 U.CARR).The lung W/D ratio were significantly (P>0.01) decreased all from 1h(4.48±0.09) to 6h(4.82±0.09). Albumin concentration in BALF were (P>0.01) decreased all from 1h(0.310±0.09mg/l)to 6h(0.390±0.05mg/l).The change was significant in 4h and 6h(P<0.01). Total cell counts in BALF were significantly (P>0.01) decreased all from 1h(6.6±1.00×107/L) to 6h(6.15±0.97×107/L). The level of TNF-ɑ in serum were significantly (P>0.01) decreased all from 1h(0.024±0.016 ng/ml) to 6h(0.061±0.021 ng/ml). The level of TNF-ɑ in BALF were decreased all from 1h(0.17±0.02 ng/ml) to 6h(0.309±0.05ng/ml). The change was significant in 4h and 6h(P<0.01). Histologically, LA can attenuate thickening alveolar walls with edema, leukocyte (PMN and monocyte) infiltration and red c...