The Role Of JNK And P38MAPK In Sevoflurane Preconditioning Inhibits TNF-α Induced ICAM-1 Expression In Vascular Endothelial Cells

Objective:To investigate the role of MAPK in sevoflurane preconditioning inhibits TNF-α induced ICAM-1 expression in vascular endothelial cells. Methods:The study is divided into three parts :(1) Human umbilical vein endothelial cells were randomly divided into 4 groups with six wells in each group: normal control group(group C),sevoflurane preconditioning group(group S), TNF-α treatment group(group T), sevoflurane preconditioning and TNF-α treatment group(group S+T),the expression level of ICAM-1 protein and the phosphorylation levels of MAPKs were measured by Western blot.(2) According to the experimental result of part one, HUVECs were randomly divided into 3 groups with four wells in each group : TNF-α treatment group(group T), sevoflurane preconditioning and TNF-α treatment group(group S+T),JNK inhibitor SP600125 and TNF-α treatment group(group SP+T),the expression of ICAM-1 and the phosphorylation level of JNK were detected by Western blot method, observing the relationship of sevoflurane preconditioning inhibits TNF-α induced ICAM-1 expression and activation of JNK.(3) HUVECs were randomly divided into 3 groups with four wells in each group : TNF-α treatment group(group T), sevoflurane preconditioning and TNF-α treatment group(group S+T),p38 MAPK inhibitor SB203580 and TNF-α treatment group(group SB+T), detecting the expression of ICAM-1 and the phosphorylation level of p38 MAPK by Western blot, and then observing the relationship of sevoflurane preconditioning inhibits TNF-α induced ICAM-1 expression and activation of p38 MAPK. Results:1. Sevoflurane pretreatment inhibited the increased expression of ICAM-1 induced by TNF-α in HUVECsCompared with group C, the expression level of ICAM-1 was significantly activated by TNF-α in group T(P<0.01), but was not significantly in group S(P>0.05);compared with group T, sevoflurane pretreatment could obviously decrease the expression level of ICAM-1 in group S+T(P<0.01).2. Sevoflurane pretreatment decreased the activated phosphorylation levels of JNK and p38 MAPK induced by TNF-α in HUVECsCompared with group C, the phosphorylation levels of JNK、p38MAPK、ERK1/2 were significantly increased in group T(P<0.01),but were not obviously in group S(P>0.05);compared with group T, the activated phosphorylation levels of JNK and p38 MAPK were significantly down-regulated(P<0.01) but the phosphorylation level of ERK1/2 was not apparently changed after sevoflurane pretreatment(P>0.05).3. JNK played an important role in the sevoflurane preconditioning inhibiting TNF-α induced ICAM-1 expressionCompared with group T, sevoflurane pretreatment significantly inhibited the expression of p-JNK and ICAM-1 in group S+T(P<0.01),and similarly JNK specific inhibitor SP600125 significantly attenuated the expression of p-JNK and ICAM-1 in group SP+T(P<0.01).4. p38 MAPK played an important role in the sevoflurane preconditioning inhibiting TNF-α induced ICAM-1 expressionCompared with group T, the expression levels of p-p38 and ICAM-1 were significantly decreased in group S+T(P<0.01),and similarly p38 MAPK specific inhibitor SB203580 significantly reduced the expression of p-p38 and ICAM-1 in group SB+T(P<0.01). Conclusion:1. Sevoflurane preconditioning inhibited the expression of ICAM-1 induced by TNF-α, suggesting that sevoflurane pretreatment could down-regulate the endothelial cell adhesion molecules, which may play an important role in reducing vascular inflammation.2. The increased phosphorylation levels of JNK and p38 MAPK were significantly down-regulated but the phosphorylation level of ERK1/2 was not significantly changed after sevoflurane pretreatment, suggesting that JNK and p38 MAPK may play a major role in anti-inflammatory effects of sevoflurane pretreatment on vascular endothelial cells in vitro.3. Treated with the specific inhibitors of JNK and p38 MAPK certificated that TNF-α induced ICAM-1 expression was related to the activation of JNK and p38 MAPK. Moreover, sevoflurane pretreatment could inhibit the activation of JNK and p38 MAPK, which finally reduced the expression of ICAM-1 and inflammatory response of vascular endothelial cells.