A study on the protective mechanisms of lipoxin A4 for hyperoxia-induced pulmonary epithelial cells injury in mice / 中国新生儿科杂志

ABSTRACT

Objective To study the protective mechanisms of lipoxin A 4 ( LXA4 ) for hyperoxia-induced lung injury through modulation of let-7c/TGF-β1 signal pathway in mice.Method MLE-12 cells was transfected with let-7c mimic, mimic negative control ( NC) , let-7c inhibitor and inhibitor NC.The cells were assigned into hyperoxia group , LXA4 group, let-7c over-expression group, let-7c silence group, let-7c silence+LXA4 group, and all exposed to 85% oxygen.The mRNA level of the extracellular matrixα-smooth muscle actin (α-SMA) and collagen Ⅰ( COL-Ⅰ) , and the expression of related genes in TGF-β1 signaling pathway (Smad 2, Smad 3, Smad 4, TGF-βR1, TGF-βR2) were examined using qPCR.The protein expressions in TGF-β1 signaling pathway was examined using Western blot .Result The mRNA expressions of α-SMA, COL-Ⅰ, Smad 3, Smad 4, TGF-βR1 and TGF-βR2 in LXA4 group [(24.3 ±2.1), (14.6 ±0.2), (17.0 ±0.0), (14.9 ±0.1), (20.8 ±0.1), (9.0 ±0.0) ] and let-7c over-expression group [ ( 12.2 ±0.5 ) , ( 3.0 ±0.0 ) , ( 3.1 ±0.0 ) , ( 9.6 ±0.4 ) , ( 28.5 ±0.2 ) , ( 7.6 ± 0.1)] were decreased comparing with the hyperoxia group [(51.4 ±0.5), (32.0 ±0.1), (40.6 ±0.2), (16.3 ±0.1), (89.1 ±1.1), (19.3 ±0.2)].These expressions were increased in both let-7c silence group [(87.3 ±7.0), (38.5 ±0.3), (48.0 ±0.2), (56.5 ±0.2), (126.0 ±0.9), (33.1 ±1.0)] and let-7c silence +LXA4 group [(144.5 ±12.9), (86.3 ±3.0), (91.5 ±4.7), (86.5 ±3.3), (109.0 ±4.5), (45.6 ±1.6)].The protein levels of Smad 2, Smad 3, Smad 4, p-Smad 2, p-Smad 3 and TGF-βR1 of LXA4 group and let-7c over-expression group were decreased comparing with the hyperoxia group, while p-Smad 2, p-Smad 3 of let-7c silence+LXA4 group were increased(P<0.05).Conclusion LXA4 may play a protective role through let-7c /TGF-β1 signal pathway of lung epithelial cells for hyperoxia-induced lung injury in mice .