The Role Of Oxidative Stress And TGFβ₁ In Hyperoxia-induced Lung Injury And The Interfering Effect Of N- Acetylcysteine On Them

ObjectiveTo find a new effective method for the protection against hyperoxia-induced lung injury in clinic, exploring the effect of oxidative stress and cytokine in the pathogenesis of lung injury and observing the interfering effect of N- acetylcysteine (NAC) on them. Methods320 neonatal SD rats of 21-day gestational age were divided into air group (Ⅰ), air+NS group (Ⅱ), air+low-dose NAC group (Ⅲ), air+high-dose NAC group (Ⅳ), hyperoxia-model group (Ⅴ), hyperoxia+NS group (Ⅵ), hyperoxia+low-dose NAC group (Ⅶ) and hyperoxia + high-dose NAC group (Ⅷ). The rats in every group were divided into the 3rd, 7th, 14th, 21st day subgroup at random. The rats in Ⅲ, Ⅳ, Ⅶ and Ⅷ groups were given NAC by administration (The high-dose was 6.25 × 10-5g/g weight every day, the low-dose was 1/4 of high-dose. The administrated time was from the 1st day to the 7th day after born.) and Ⅱ, Ⅵ groups were given NS. Ⅰ, Ⅱ, Ⅲ, Ⅳ groups were fed in air; Ⅴ, Ⅵ, Ⅶ, Ⅷ groups were fed in hyperoxide ( > 95%) condition. The rats of every group were drawn for examples respectively at every time spot. The lung histopathology were observed by light microscope; the alteration of ultrastructure was observed by transmission electron microscope; the levels of 8-iso-PGF2a in plasm were measured by ELISA and the expression of TGFβ1, collagen Ⅰ, collagen Ⅲ in lungs were measured by immunohistochemistry. Results1. In Ⅴ group, the inequality of size of lung alveoli, hemorrhage and inflammatory cell infiltration in lung alveoli were observed on the 3rd and 7th day. The thick alveolar septum was observed in the hyperoxic-damaged lungs of the 14th day and the 21st day. The consequence of electron microscope showed swollen mitochondria, empty lamellar bodies in type Ⅱ alveolar epithelial, and massive procollagen fibers deposited in the extracellular matrix in the 14th and 21st day. Compared with Ⅴ group, the pathomorphism of lungs in Ⅷ group was abatement and that of Ⅶ group was resemble.a2. Compared with Ⅰ group, the level of 8-iso-PGF2a of blood plasm in Ⅴ group was higher significantly at every time spot (P<0.01) . The level of 8-iso-PGF2a of blood plasm in Ⅴ group was higher than that of Ⅷ group on the 3rd, 7th and 14th day (P= 0.007,0.027,0.000) .3. PU values of TGFβ1 expression had no statistically significant between every group (P> 0.05) ; On the 7th, 14th, 21st day, PU values of TGFβ1 positive expression in Ⅴ group were higher significantly than that in Ⅰ group (P<0.001) , but that of Ⅷ group were lower significantly than that of Ⅴ group (P=0.000,0.000, 0.015) .4. PU values of collagen I expression at every time spot had no statistically significant between every group on the 3rd and 7th day (P > 0.05) ; On the 14th and 21st day, the expression of　Ⅴ group was higher significantly than that of I group (P<0.01) ; but that of 　Ⅷ group was lower than that of Ⅴ group (p=0.015, 0.001) .5. PU values of collagen Ⅲ expression at every time spot had no statistically significant between every group on the 3rd day (P>0.05) ; on the 7th, 14th and 21st day, the expression of Ⅴ group was higher significantly than that of Ⅰ group (P<0.01); but that of Ⅷ group was lower significantly than that of Ⅴ group (P<0.01) .6. Compared Ⅴ group and Ⅶ group, the levels of 8-iso-PGF2a of blood plasm, the expression of TGFβ1, collagen Ⅰ, and collagen Ⅲ had no statistically significant in the same time spot.ConcIusion1. Hyperoxia exposure can cause lung damage. Hyperoxia could induce the changes: dyssynthesis of type II alveolar epithelial cell, and the deposition of collagen in extracellular matrix.2. Hyperoxia-induced lung injury is the consequence caused by mutual effect and interaction of oxidative stress, TGFβ1, and so on.3. NAC maybe has interventional effect on many joint of the pathological process of hyperoxia-induced lung injury and its protecting effect has dose dependence.