The Effects Of Inhaled Prostaglandin E₁ On Th1/Th2 Lipopolysaccharide Induced Acute Lung Injury In Rats

Objective To investigate the effects of inhaled Prostaglandin E₁ on Th1/Th2 lipopolysaccharide induced acute lung injury in rats, and to approach the mechanisms of prostaglandin E₁ therapy for actue lung injury.Methods All male healthy adult Wistaer rats [weight (200±20)g] were random divided into normal sodium contrast (NS) group, lipopolysaccharide (LPS) group and inhaled Prostaglandin E₁ (PGE₁) group.The model of ALI were made by injecting LPS every kilogram 5 milligram into caudal vein, the NS group were injected normal sodium 5 millilitre every one by caudal vein. The rats of PGE₁ group free inhaled Prostaglandin E₁ after 30 minutes injected LPS in the big glass bottle, which to be continue filled with aerosolized Prostaglandin E₁ (0. 4μg/ml), 30 minutes every time , and after 12 hours the still live rats to repeat do it, whereas the rats of the NS group and LPS group inhaled aerosolized normal sodium by the same way.Subsequently at 1h, 6h, 12h and 24h, respectively, the right lung median lobe to obtain to calculate W/D value; and pathological examination of lung tissues that was from the right lung inferior lobe to stained by HE was made under light microscope; ELISA was empolyed to measure the level of IFN-γwhich represent the change of cytokine Th1, and level of IL-4 which represent the change of cytokine Th2 in the serum and broncho-alveolar lavage fluid (BALF), and calculate the ratio of IFN-γ/IL-4 which represent the change of cytokine Th1/Th2; the white blood cell(WBC)and polymorphonuclear neutrophils(PMN) were measured by autokinetic movement blood cell analysator at the same time in the serum and BALF.Results (1)The value of lung W/D: Statistic analysis showed that the W/D value in LPS group were higher than those in NS group at 6h, 12h and 24h(p<0. 01) ; while in PGE₁ group lower than those in LPS group at 12h and 24h (p<0.01).(2) The value of WBC and PMN in the serum and BALF: Compared with NS group, the WBC and PMN in the serum and BALF of LPS group were significant increased at all hours(p<0.01). but compared with LPS group, the WBC in the serum was decreased at 6h, 12h, 24h (p<0.05), the PMN in the serum was significant decreased at 6h, 12h and 24h (p<0.01), the WBC in the BALF was significant decreased at all hours (p<0.01), and the PMN in the BALF was significant decreased at 6h, 12h and 24h (p<0.01) in the PGE, group.(3) The level of IFN-γ(Th1),IL-4(Th2) and the ratio of IFN-γ/IL-4 (Th1/Th2) in the serum and BALF: Statistic analysis showed that the ratio of IFN-γ/IL-4 (Th1/Th2)in the LPS group increased significantly by Compared with NS group in the serum and BALF(P<0.01) ; while, Compared with LPS group, the level of IFN-γ(Th1) in serum was significant decreased at 12h and 24h (P<0.01), the level of IL-4(Th2) in serum was increased at 12h and 24h (p<0.05), the ratio of IFN-γ/IL-4(Th1/Th2) in serum was degraded significantly at 6h, 12h and 24h (P<0.01), and in the BALF, the level of IFN-γ(Th1) was significant decreased at 6h, 12h and 24h (P<0.01), the level of IL-4(Th2) was significant decreased at 24h (P<0.01), and the ratio of IFN-γ/IL-4(Th1/Th2) was degraded significantly at all hours (P<0.01) in the PGE, group.Conclusion Pathological examination of lung tissue proved that ALI had occurring by injecting LPS into caudal vein. the level of IFN-γ(Th1) and IL-4(Th2) in the serum or BALF has increased by LPS induced ALI, and the imbalance of Th1/Th2 type cytokines was found in the LPS induced ALI; inhaled Prostaglandin E₁ can convalescence the imbalance by lighten the PMN keep in custody at lung and degraded the membrane permeability of alveolar capillary membrane, it can be correspondence decreased the level of IFN-γ(Th1), and correspondence increased the level of IL-4(Th2) in the serum or BALF, and the cytokines of Th1 maybe toward to drift Th2. It proof that inhaled Prostaglandin E₁ can utility therapy and protection the rats of ALI induced by LPS.