The intervention effect of Tibetan medicine Siwei Huangqi powder on hypoxic pulmonary hypertension through autophagy signaling pathway induced by AMPK protein / 中国药理学通报

ABSTRACT

Aim To explore the mechanism of Tibetan medicine Siwei Huangqi powder(SW)in reducing hypoxic pulmonary hypertension. Methods A total of 110 Wistar rats were randomly divided into normoxia control group,hypoxic control group and hypoxic drug group. The two hypoxic groups were divided into 1,3,7,15 and 30 day group according to the exposure time of hypoxic,10 groups in total. The normoxia control group was placed in the atmospheric environment at an altitude of 2 260 meters without intervention; 10 hypoxic groups were placed in a hypobaric hypoxic chamber with a simulated altitude of 5 000 meters. The hypoxic drug group was given SW suspension(0.42 g/100 g)by gavage,and the hypoxic control group was given normal saline by gavage,once a day. The Ppa and RV/(LV+S)were measured at the corresponding time points in each group; the levels of p-AMPK,ULK-1 and LC3 /LC3 Ⅱ protein in lung tissues were measured by WB method. Results Compared with normoxia control group,the ratio of PA and RV/(LV + s)in hypoxic control group increased gradually with the extension of hypoxic exposure time,which was consistent with the thickness of pulmonary artery smooth muscle layer and the changes of pulmonary tissue subcellular organelles. The expression level of p-AMPK protein in lung tissues was also slightly up-regulated(P<0.05),and ULK-1 and LC3 Ⅱ were significantly up-regulated(P<0.01),especially in acute hypoxic. Compared with the hypoxic control group,the increase of Ppa and the thickening of pulmonary artery smooth muscle layer in the hypoxic drug group were significantly reduced(P<0.050.01),while the expression levels of p-AMPK,ULK-1 and LC3 Ⅱ proteins in lung tissues increased with the extension of hypoxic exposure time(P<0.050.001),especially in chronic hypoxic. Conclusion SW can inhibit hypoxic pulmonary hypertension by up-regulating AMPK autophagy signaling pathway.