Effects of Panax Notoginseng Total Saponins on PASMCs Autophagy through AMPK Pathway
SHI Xiaoqian1#, SONG Zhengyang2#, TIAN Yunna2, WANG Xinyu2, ZHANG Sai2, ZHANG Congcong3, WANG Wantie2*
This study investigated the regulation mechanism of Panax notoginseng total saponins on autophagy of rat PASMCs (pulmonary artery smooth muscle cells) and the intervention on PASMCs proliferation and apoptosis under hypoxia and high carbon dioxide conditions. The rat PASMCs were randomly divided into five groups after starvation treatment: normal control group (N), model group (HH), AMPK agonist AICAR group (AI), Panax notoginseng total saponins group (PNS) and Panax notoginseng total saponins combined with AMPK agonist group (PA). After corresponding treatment, cell survival rate of each group was measured by CCK-8. AMPK, mTOR, LC3, p62 and Caspase-3 were detected by qRT-PCR, and the protein expression levels of AMPK, p-AMPK,mTOR, p-mTOR, LC3, p62, Caspase-3 and PCNA were detected by Western blot. Autophagosomes were observed by transmission electron microscopy. The results showed that compared with HH group, the expression of Caspase-3 was up-regulated and the expression of PCNA was down-regulated in PNS group, suggesting that PNS could promote the apoptosis of PASMCs and inhibit its proliferation. In the PNS group, AMPK-mTOR signaling pathway was down-regulated and autophagy level decreased, indicating that PNS could down-regulate AMPK-mTOR pathway activity and inhibit autophagy level. Compared with PNS group, the level of autophagy in PA group was increased, the proliferation was up-regulated, and the apoptosis was decreased, suggesting that PNS might inhibit the proliferation of PASMCs induced by hypoxia and high carbon dioxide in rats by down-regulating AMPK-mTOR signaling pathway to inhibit autophagy and promote apoptosis.
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