PHC inhibits the defects of alveolar type II epithelial cells and activation of ERK in lung tissue of ALI rat induced by LPS

AIM: To investigate the effects of penehyclidine hydrochloride (PHC) on lipopolysaccharide (LPS) induced the changes of ultrastructure of alveolar type II epithelial cells (ATII) and activation of extracellular signal-regulated protein kinase (ERK) in lung tissue in rats. METHODS: Acute lung injury (ALI) was induced successfully by intravenous administration 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. The changes of ultrastructure of ATII, lung permeability index (LPI), wet to dry weight (W/D) ratio in lung were measured at 6 h after LPS application. Western blotting analysis was performed to determine the phosphorylations of ERK in lung tissue at 6 h after LPS application. To examine whether the effects of PHC on activation of ERK 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 level of phosphorylated ERK. RESULTS: Challenge with LPS alone resulted in a significant increase in W/D ratio in lung and LPI. The defects of ATII with no lamellar bodies in cytoplasm, the lack of microvilli along its margin, severely swollen endoplasmic reticulum, nuclear cisterna and loss of integrity of the basement membrane induced by LPS were observed under transmission electron microscope. LPS also triggered activation of ERK at 2 h. Pre-treatment with PHC significantly abolished increase in W/D ratio in lung, LPI and attenuated pathological changes of ATII in a dose-dependent manner. Moreover, pre-treatment with PHC efficiently blunted the activation of ERK induced by LPS at 6 h. CONCLUSION: These results suggest that pre-treatment with PHC significantly attenuates the lung permeability and defects of ATII in LPS-induced ALI in rats, and these effects are partly responsible for the inhibition of ERK activation by LPS.