Abstract:

Objective

To explore the effect and mechanism of Wuling powder on hypoxia induced high altitude cerebral edema （HACE）.

Methods

Forty healthy male SD rats were randomly divided into four groups using a random number table： normobaric normoxic group （NC group）， high-altitude cerebral edema group （HACE group）， low-dose Wuling powder intervention group （WP-L group）， and high-dose Wuling powder intervention group （WP-H group）， with 10 rats in each group. The NC group was normally housed under normal pressure and oxygen conditions， while the remaining three groups were housed in a low-pressure， low-oxygen animal chamber which simulated the low-temperature and hypoxic environment of the plateau at an altitude of 6000 m to establish a plateau cerebral edema model. The rats in WP-L and WP-H groups were given 260 and 780 mg/kg of Wuling powder by gavage continuously 4 d before and 3 d after entering the cabin， respectively. HACE group was given the same amount of physiological saline.After 7 d， the brain water content was measured using the dry wet mass method， and the degree of brain function damage in rats was evaluated using the modified neurological severity score （mNSS） and corner test. The level of superoxide dismutase （SOD） in the cortical brain tissue of rats was detected using the microcalorimetry method， and the level of malondialdehyde （MDA） was detected using the colorimetric method. The mRNA relative expression levels of inflammatory factors interleukin （IL）-1β， IL-6， and tumor necrosis factor α （TNF-α） in the cortical brain tissue of rats were detected using qPCR experiment. The expression of aquaporin-4 （AQP4）， protein kinase D1 （PKD1）， and hypoxia inducible factor-1α （HIF-1α）in the cortical brain tissue of rats was determined using Western blot experiment.

Results

After 72 h of low-temperature and low oxygen environment feeding， the brain water content of rats in the WP-L group and WP-H group was significantly lower than that in the HACE group， and the difference was statistically significant （P＜0.05）. The mNSS score of HACE group rats was significantly higher than that of NC group，and the proportion of left turn was significantly increased； the mNSS scores of rats in the WP-L and WP-H groups were significantly lower than those in the HACE group， and the proportion of left turn was significantly reduced， with statistically significant differences （P＜0.05）. The MDA level in the brain tissue of HACE group rats was significantly higher than that of NC group， and the SOD activity was significantly decreased； the MDA level in the brain tissue of rats in both WP-L and WP-H groups decreased significantly， while the SOD activity increased significantly， and the differences were statistically significant （P＜0.05）. The levels of IL-1β， IL-6， and TNF-α in the HACE group were higher than those in the NC group， while the mRNA levels of various inflammatory factors in the WP-L and WP-H groups were significantly lower than those in the HACE group， and the differences were statistically significant （P＜0.05）. The expression of AQP4， HIF-1α， and PKD1 proteins in the HACE group was significantly increased compared to the NC group； the expression of AQP4， HIF-1α， and PKD1 proteins in the WP-L and WP-H groups gradually decreased compared to the HACE group， and the differences were statistically significant （P＜0.05）.

Conclusions

Wuling powder can significantly reduce cerebral edema and neurological impairment in HACE rats， and its mechanism of action may be related to the modulation of the HIF-1α/PKD1 pathway to play a role in alleviating oxidative stress injury， reduce inflammatory response， and ultimately play a role in improving hypoxia-induced plateau cerebral edema.

Key words: High altitude cerebral edema, Wuling powder, Oxidative stress, Inflammatory factor