Penehyclidine hydrochloride inhibits activation of p38MAPK in rat lung tissue with ALI induced by LPS

AIM:To investigate the effects of penehyclidine hydrochloride (PHC) on lipopolysaccharide (LPS) induced activation of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK) in lung tissue in rats.METHODS:Acute lung injury (ALI) was induced successfully by intravenous administraiton of LPS (5 mg/kg) in rats. PHC (3.0,1.0,and 0.3 mg/kg) was administered to rats 0.5 h prior and then again concomitant with LPS exposure. Western blotting analysis was performed to determine the phosphorylations of p38MAPK and JNK in lung tissue at 6 h after LPS application. To examine whether the effects of PHC on activation of p38MAPK and JNK was in a time-dependent manner,lung tissues at 0 h,2 h,4 h,6 h,and 12 h were collected for measuring the levels of phosphorylated p38MAPK and JNK.RESULTS:Challenge with LPS alone triggered the activation of p38MAPK and JNK in 2 h. Pretreatment with PHC effectively inhibited the activation of p38MAPK induced by LPS at 6 h. However,PHC did not efficiently inhibit the activation of JNK induced by LPS.CONCLUSION:These results suggest that the protective effect of PHC in LPS-induced ALI in rats is partly responsible for the inhibition of the activation of p38MAPK by LPS.