Abstract： Objective To evaluate the protective effect of dental pulp stem cells(DPSCs)against high-altitude pulmonary edema(HAPE)and explore the mechanism.Methods Twenty-one Sprague-Dawley rats were randomly divided into the normal control group(Control),high altitude pulmonary edema group(HAPE)and DPSC prevention group(DPSC).Three days and one day before the hypobaric and hypoxia environment was simulated,DPSCs were administrated via the tail vein in the DPSC group,and phosphate buffered saline(PBS)of the same volume was injected in the control group and HAPE group.After that,rats in the HAPE group and DPSC group were placed in a simulated hypobaric and hypoxic cabin to simulate the environment at an altitude of 6000 m before an HAPE model was established.The rats were sacrificed 3 days later,and the histopathological changes of lung tissue were observed via hematoxylin-eosine(HE)staining.The dry/wet weight of lung tissues was recorded.The concentrations of total protein in lung homogenate were detected using the BCA method.The expression of aquaporin 1(APQ-1)in lung tissue was detected by real-time reverse transcription polymerase chain reaction(RT-PCR)and Western blotting.Colorimetry and enzyme linked immunosorbent assay(ELISA)were used to detect the concentrations of plasma vasoactive substances.The expression of inflammatory factors in serum and lung tissue was detected by ELISA and RT-PCR respectively.Results After three days of treatment in a simulated hypobaric and hypoxic environment,the lung tissue of the HAPE group showed infiltration of inflammatory cells,alveolar wall thickening,alveolar septum thickening and increases of exudation.DPSC prevention could significantly reduce the histopathological damage to the lung.Lung water content(LWC)and total protein content of lung homogenate were significantly increased in the HAPE group but obviously reduced in the DPSC prevention group,and the difference between the two groups was statistically significant(P＜0.01).The protein and mRNA expression levels of AQP-1 in lung tissue of the HAPE group were significantly decreased,but prevention via DPSCs could enhance the expression of AQP-1 in lung tissue.In the HAPE group,the concentrations of nitrous oxide(NO)and prostacyclin(PGI2)in plasma were significantly decreased,but prevention via DPSCs could significantly increase the expression of plasma vasoactive substances.The expressions of inflammatory factors interleukin-1 α(IL-1α)and tumor necrosis factor-α(TNF-α)in serum and lung tissue of the HAPE group increased significantly,but decreased in the DPSC prevention group.Conclusion DPSCs can help prevent high-altitude pulmonary edema in rats by promoting the expression of aquaporin,increasing the content of vasodilators in plasma and reducing the expression of inflammatory factors in serum and lung tissue.