Propofol Effect On Nf-kb Activity Of Cells Of Acute Lung Injury Model

Acute lung injury(ALI)is a kind of inflammatory syndrome clinically characterized as increase in blood vessel permeability. It induced by various dangerous factors (such as serious infected and shock) outside pulmonary system with complicated pathogenesis. Until now there has none effective therapy and the mortality is more than 50%. Pulmonary alveolar macrophages(PAM)widely distributed in alveoli and in the surface of tracheal epithelial cells. They play very important roles in the process of immune defense and lung injury in bronchoalveoli. During the early period of inflammation, trauma shock and lipopolysaccharide(LPS) can activated PAM to release various proinflammatory cytokines, one of them is tumor necrosis factor-α(TNF-α), which lead to uncontrolled inflammatory reaction and induced ALI/ARDS. Nuclear factor kappa B(NF-ΚB) is a kind of eukaryon cell transcription factor which is very important in gene transcription ,and it transported to the cell nucleus by extra cellular stimulus such as LPS, shock and so on through signal transmission pathway. It promotes and regulates the gene transcription some inflammatory mediators(TNF-α,IL-8,etc) and it closed to ALI. Propofol is a new kind anesthesia drug, which is widely used in operation in recent years. Propofol can alleviate the damage caused by LPS-induced acute lung injury and have some anti-inflammation effect. But it is not seen whether propofol influent the NF-ΚB activation channel. This study observes the influence of propofol on activation of NF-ΚB caused by LPS anti-inflammation mechanism on the cell level. At the meantime ,we discuss the activation pathway of NF-ΚB and the possible anti-inflammation mechanism of propofol in acute lung injury. Methods: PAM of rats were cultured and divided into four group:(1) LPS group (induced byLPS10μg/ml);(2) Propofol+LPS group1 (induced byLPS10μg/ml and propofol 1μg/ml); Propofol+LPS group2 (induced byLPS10μg/ml and propofol 4μg/ml); Propofol+LPS group3(induced byLPS10μg/ml and propofol 16μg/ml).The NF-ΚB activity of PAM and the concentration of TNF-αin the supernatant were measured by immunohistochemistry and ELISA after induced 0.5,1,2,4hour. Result: The NF-ΚB level in LPS stimulation group has a rise in 1 hour after stimulate and reach to the peak after 2 hours, at the meantime the TNF-αlevel also has a rise. In propofol interference group, NF-ΚB activity and TNF-αlevel were markedly lower than those in LPS stimulation group(p<0.05). With the protocol's increasing the inhibition has become more obviously. Conclusion: After the stimulation of LPS on PAM, NF-ΚB activation and TNF-αrelease occur. The NF-ΚB rapidly activation is probably the key step for PAM release a large amount of inflammatory factor such as TNF-α,which is very important to acute lung injury. Propofol restricts the effect of LPS and functions in the ALI cell model as inflammatory inhibitor, inhibits the activation of NF-ΚB and alleviate the damage to PAM. At the same time it make PAM release less TNF-αand have some anti-inflammation effect.