Sodium tanshinone ⅡA sulfonate inhibits the proliferation of hypoxia-induced PASMC of rat and its potential mechanism
YANG Lei 1, ZHENG Jin-xu 1, SHI Xiao-dong 1, QIAN Hai 2, SUN Jin-ling 1
(1. Department of Respiratory Medicine, the Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212001; 2. School of Medicine, Jiangsu University, Zhenjiang Jiangsu 212013, China)
Abstract:Objective: To investigate the effect of sodium tanshinone ⅡA sulfonate(STS) on the proliferation of rat pulmonary arterial smooth muscle cells(PASMC) induced by hypoxia and its potential mechanism. Methods: Rat PASMC were selected for the following experiments. First, PASMC were divided into normoxia control group, hypoxia group(3%O 2 ), normoxia control +STS low-, medium-and high-dose groups(5, 10, 20 ng/mL). After cultured for 60 h, the proliferation of PASMC was determined by CCK-8. Then, PASMC were divided into normoxia control group, hypoxia group(3%O 2 ), hypoxia +STS group(10 ng/mL), qRT-PCR was used to detect the mRNA expressions of mTOR, eIF2α, c-myc. In mechanism study test, PASMC were divided into normoxia control group, hypoxia group(3%O 2 ), hypoxia +STS group(10 ng/mL), hypoxia +rapamycin group(20 nmol/L); Western blotting were used to investigate the expressions of mTOR, p-mTOR, eIF2α, p-eIF2α, c-myc in PASMC. Results: Compared with normoxia control group, cell viability in hypoxia group increased significantly(P<0.05); compared with hypoxia group, cell viability in STS group decreased significantly(P<0.05). qRT-PCR showed the mRNA expression of mTOR, eIF2α and c-myc in hypoxia group increased significantly in contrast to normoxia control group(P<0.05); compared with hypoxia group, the three mRNAs expression in STS group decreased significantly(P<0.05). In Western blotting, compared with normoxia control group, the expression of mTOR, p-mTOR, eIF2α, p-eIF2α, c-myc increased significantly in hypoxia group(P<0.05); while in contrast to hypoxia group, the expression of mTOR, p-mTOR, eIF2α, p-eIF2α, c-myc decreased significantly(P<0.05); there was no statistical significance between hypoxia+STS group and hypoxia+rapamycin group(P>0.05). Conclusion: STS could inhibit hypoxia-induced proliferation of PASMC by suppressing mTOR/eIF2α signaling pathway. [Key words]rat pulmonary arterial smooth muscle cells; sodium tanshinone ⅡA sulfonate; mTOR/eIF2α; c-myc
杨磊1, 郑金旭1, 史小东1, 钱海2, 孙金玲1. 丹参酮ⅡA磺酸钠抑制低氧诱导的大鼠肺动脉平滑肌细胞增殖及其机制[J]. 江苏大学学报:医学版, 2008, 28(03): 190-194.
YANG Lei-1, Zheng-Jin-Xu-1, Shi-Xiao-Dong-1, Qian-Hai-2, Sun-Jin-Ling-1. Sodium tanshinone ⅡA sulfonate inhibits the proliferation of hypoxia-induced PASMC of rat and its potential mechanism. Journal of Jiangsu University(Medicine Edition), 2008, 28(03): 190-194.