EGCG Effects On The Expressions Of MAPK,c-Fos And HO-1 In The Lungs Of Rabbits With Oleic-acid-induced ARDS

Objective: Acute respiratory distress syndrome (ARDS) is the manifestation of systemic inflammatory response syndrome (SIRS) in the lung, and the over-activation of NF- κ B signal transduction pathways plays an important role in the occurrence of ARDS. We found in the lungs of rabbits with oleic-acid -induced ARDS, NF- κ B, TNF-, and IL-1 were highly expressed, and after inhaled with EGCG, the expressions of NF- κ B, TNF-, and IL-1 were inhibited, which resulted in alleviation of inflammation in the lung tissue.Mitogen-activated protein kinase (MAPK), as a kind of serine proteinnase (threonine proteinnase), exists in the most cells and plays a role in the inflammatory regulation. MAPK can transfer activation signals from extracellular to intracellular and nucleus. At present, four MAPK signal pathways were found: (1) ERK (extracellular signal-regulated kinase ) signal pathway;(2) JNK/SAPK signal pathway;(3) p38MAPK signal pathway, similar to JNK;(4)ERK5 signal pathway, seldom studied. The previous study has proved that JNK/SAPK and p38MAPK mainly participate in the immune regulation, inflammatory reaction, and apoptosis under the condition of oxidation and stress response. In this study, we used these two signal pathways toexplore the mechanism of pathological change in the lung during ARDS and effects of EGCG on the two pathways.Hemo oxygenase ( HO-1) is a kind of initial enzyme and rate-limiting enzyme, which catalyzes hemachrome into carbon monoxide, iron, and cholerythrin. A study has proved that HO-1 has protective effects on tissues. Intracellular transcription factor, such as NF- k B, and AP-1, can regulate both inflammatory cytokines and antioxidation factors, such as HO-1, Y-GCS. In this study, we observed the HO-1 expression in the lung of rabbits with ARDS, and effects of EGCG on it.Methods: 57 healthy adult rabbits were randomly divided into EGCG gavage group, EGCG inhalation group, and control group. ARDS models were produced by intravenously injected with 20% oleic acid. Blood was collected for blood analysis at 1, 2, 3, 4 hours after mechanical ventilation, the experiment finished at 4 hours after ventilation, and the rabbits were killed. The lung was collected for gross specimen and pathological specimen. HE staining and immuo-histochemical method were used. The expressions of P38MAPK, JNK1, c-Fos, and HO-1 in the lung were observed.Results: (1) PaO2 and PaCO2 The effect of grouping factor and time factor on the experiment was significant(P<0.01), and the interaction between grouping factor and time factor was also significant (P<0.0\);there was no significant difference between control group and EGCG gavage group CP>0.05 );there was significant difference between control group and EGCG inhalation group, between EGCG inhalation group and EGCG gavage group. There was no significant difference on PaCO2 between the three groups at 1 and 2 hours after ventilation (P>0.05);there was significant difference between lh and 3 h, between 4 h, 2 h and 3h, between 4 h, 3 h and 4 h (PO.01);there existed difference at 1,2,3,4 hours (PO.01) . (2) The gross specimen of lung showed that diffuse hemorrhage, hyperemia, and pathological changes were slighter in the EGCG inhalation group than those incontrol group and EGCG gavage group. (3) Under light microscopy, in the control group and EGCG gavage group there were edema, blood cell infiltration, and inflammatory cell infiltration the thickened alveolar wall;pulmonary interstitium had edema and was thickened;alveolar epithelium was swollen, some alveolus were collapsed and the structure was destroyed. This was slighter in the EGCG inhalation group. (4) The positive expression of P38MAPK in the control group and EGCG inhalation group was (85.44±2.88)% and (77.89+2.26)%, respectively, and there was no significant difference between control group and EGCG gavage group (P> 0.05). The positive expression of JNKi in the control group and EGCG inhalation group was (77.89±2.26)% and (23.69 + 2.57)%, respectively, and there was no significant difference between control group and EGCG gavage group (/>>0.05). The positive expression of c-Fos in the control group and EGCG inhalation group was (45.44 ±3.24)% and (15.69 ± 1.78)%, respectively, and there was no significant difference between control group and EGCG gavage group (P>0.05). The positive expression of HO-1 in the control group and EGCG inhalation group was (85.33 + 2.45)% and (43.19±2.83)%, respectively, and there was no significant difference between control group and EGCG gavage group (P>0.05)Conclusion: (1) The inhalation of EGCG can alleviate the lung injury, and has protective effects on the lung of rabbits with oleic-acid-induced ARDS. (2) EGCG can inhibit the positive expression of P38MAPK, JNKi, and c-Fos in the lung tissue, reduce the expression of inflammatory factors, restrain inflammatory reaction in the lung tissue, and alleviate pathological changes of ARDS. (3) After inhalation of EGCG, the protective reaction of organism is weakened, and the expression of HO-1 is reduced. (4) The gavage of EGCG has no protective effects on on the lung of rabbits with oleic-acid-induced ARDS.